Unit 11 Reproduction and Development

 

Small, uncoordinated, and slick with amniotic fluid, a newborn encounters the world outside of her mother’s womb. We do not often consider that a child’s birth is proof of the healthy functioning of both her mother’s and father’s reproductive systems. Moreover, her parents’ endocrine systems had to secrete the appropriate regulating hormones to induce the production and release of unique male and female gametes, reproductive cells containing the parents’ genetic material (one set of 23 chromosomes). Her parent’s reproductive behaviour had to facilitate the transfer of male gametes—the sperm—to the female reproductive tract at just the right time to encounter the female gamete, an oocyte (egg). Finally, combination of the gametes (fertilization) had to occur, followed by implantation and development. In this unit, you will explore the male and female reproductive systems, whose healthy functioning can culminate in the powerful sound of a newborn’s first cry.

 

Part 1: Anatomy and Physiology of the Male Reproductive System

Unique for its role in human reproduction, a gamete is a specialized sex cell usually carrying 23 chromosomes—one half the number in somatic cells. At fertilization, the chromosomes in one male gamete, called a sperm (or spermatozoon), combine with the chromosomes in one female gamete, called an oocyte. The function of the male reproductive system (Figure 1) is to produce sperm and transfer them to the female reproductive tract. The paired testes are a crucial component in this process, as they produce both sperm and androgens, the hormones that support male reproductive physiology. In humans, the most important male androgen is testosterone. Several accessory organs and ducts aid the process of sperm maturation and transport the sperm and other seminal components to the penis, which delivers sperm to the female reproductive tract. In this section, we examine each of these different structures, and discuss the process of sperm production and transport.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Scrotum

The testes are located in a highly pigmented, muscular sac called the scrotum that extends from the body behind the penis (Figure 1). This location is important in sperm production, which occurs within the testes, and proceeds more efficiently when the testes are kept 2 to 4°C below core body temperature.

Testes

The testes (singular = testis) are the male gonads. They produce both sperm and androgens, such as testosterone, and are active throughout the reproductive lifespan of the male.

As paired oval organs, the testes are each approximately 4 to 5 cm in length and are housed within the scrotum (Figure 2). Within the testes, sperm develop in structures called seminiferous tubules. During the seventh month of the developmental period of a male fetus, each testis moves through the abdominal musculature to descend into the scrotal cavity. This is called the “descent of the testis.”

The tightly coiled seminiferous tubules form the bulk of each testis. They are composed of developing sperm cells surrounding a lumen, the hollow centre of the tubule, where formed sperm are released into the duct system of the testis (Figure 3). Specifically, from the lumens of the seminiferous tubules, sperm move into the straight tubules then into a fine meshwork of tubules and then leave the testis itself.

Inside the seminiferous tubules are supporting cells and developing sperm cells called germ cells. Germ cell development progresses from the basement membrane—at the perimeter of the tubule—toward the lumen.

1. Sertoli Cells: Surrounding all stages of the developing sperm cells are elongate, branching Sertoli cells. Sertoli cells secrete signaling molecules that promote sperm production and can control whether germ cells live or die.

2. Germ Cells: The least mature cells line the basement membrane inside the tubule. These divide to produce primary and secondary spermatocytes, then spermatids, which finally produce formed sperm. This process is called spermatogenesis. The process begins at puberty, after which time sperm are produced constantly throughout a man’s life. Eventually, the sperm are released into the lumen and are moved along a series of ducts in the testis toward a structure called the epididymis for the next step of sperm maturation.

Structure of Formed Sperm

Sperm are smaller than most cells in the body; in fact, the volume of a sperm cell is 85,000 times less than that of the female gamete. Approximately 100 to 300 million sperm are produced each day, whereas typically only one oocyte per month matures fully and is then ovulated. As is true for most cells in the body, the structure of sperm cells speaks to their function. Sperm have a distinctive head, mid-piece, and tail region (Figure 4). The head of the sperm contains the extremely compact haploid (half the genetic content of a diploid somatic cell) nucleus with very little cytoplasm. These qualities contribute to the overall small size of the sperm (the head is only 5 μm long). A structure called the acrosome covers most of the head of the sperm cell as a “cap” that is filled with lysosomal enzymes important for preparing sperm to participate in fertilization. Tightly packed mitochondria fill the midpiece of the sperm. ATP produced by these mitochondria will power the flagellum, which extends from the neck and the mid-piece through the tail of the sperm, enabling it to move the entire sperm cell.

Sperm Transport

To fertilize an oocyte, sperm must be moved from the seminiferous tubules in the testes, through the epididymis, and—later during ejaculation—along the length of the penis and out into the female reproductive tract.

1. Role of the Epididymis: From the lumen of the seminiferous tubules, the immotile sperm are surrounded by testicular fluid and moved to the epididymis (plural = epididymides), a coiled tube attached to the testis where newly formed sperm continue to mature (Figure 3). Though the epididymis does not take up much room in its tightly coiled state, it would be approximately 6 m (20 feet) long if straightened. It takes an average of 12 days for sperm to move through the coils of the epididymis. Sperm enter the head of the epididymis and are moved along predominantly by the contraction of smooth muscles lining the epididymal tubes. As they are moved along the length of the epididymis, the sperm further mature and acquire the ability to move under their own power. Once inside the female reproductive tract, they will use this ability to move independently toward the unfertilized egg. The more mature sperm are then stored in the tail of the epididymis (the final section) until ejaculation occurs.

2. Duct System: During ejaculation, sperm exit the tail of the epididymis and are pushed by smooth muscle contraction to the ductus deferens (also called the vas deferens). The ductus deferens is a thick, muscular tube that is bundled together inside the scrotum with connective tissue, blood vessels, and nerves into a structure called the spermatic cord (Figure 1 and Figure 2). Surgical sterilization to interrupt sperm delivery can be performed by cutting and sealing a small section of the ductus (vas) deferens. This procedure is called a vasectomy, and it is an effective and usually permanent form of male birth control.

From each epididymis, each ductus deferens extends superiorly into the abdominal cavity through the inguinal canal in the abdominal wall. From here, the ductus deferens continues posteriorly to the pelvic cavity, ending posterior to the bladder where it dilates in a region called the ampulla (meaning “flask”).

Sperm make up only 5 percent of the final volume of semen, the viscous, whitish-gray fluid that the male ejaculates. The bulk of semen is produced by three critical accessory glands of the male reproductive system: the seminal vesicles, the prostate, and the bulbourethral glands.

3. Seminal Vesicles: As sperm pass through the ampulla of the ductus deferens at ejaculation, they mix with fluid from the associated seminal vesicle (Figure 1). The paired seminal vesicles are glands that contribute approximately 60 percent of the semen volume. Seminal vesicle fluid contains large amounts of fructose, which is used by the sperm mitochondria to generate ATP to allow movement through the female reproductive tract.

The fluid, now containing both sperm and seminal vesicle secretions, next moves into the associated paired ejaculatory ducts, which transport the seminal fluid into the next structure, the prostate gland.

4. Prostate Gland: The centrally located prostate gland sits anterior to the rectum at the base of the bladder surrounding the prostatic urethra, the portion of the urethra that runs within the prostate (Figure 1). About the size of a walnut, the prostate is formed of both muscular and glandular tissues. It excretes a fluid enriched with enzymes and citric acid to the passing seminal fluid—now called semen—that is critical to first coagulate and then decoagulate the semen following ejaculation. The temporary thickening of semen helps retain it within the female reproductive tract, providing time for sperm to utilize the fructose provided by seminal vesicle secretions. When the semen regains its fluid state, sperm can then pass farther into the female reproductive tract.

5. Bulbourethral Glands: The final addition to semen is made by two bulbourethral glands (or Cowper’s glands) that release a thick, salty fluid that lubricates the end of the urethra and the vagina and helps to clean urine residues from the penile urethra. The fluid from these accessory glands is released after the male becomes sexually aroused, and shortly before the release of the semen. It is therefore sometimes called pre-ejaculate. It is important to note that, in addition to the lubricating proteins, it is possible for bulbourethral fluid to pick up sperm already present in the urethra, and therefore it may be able to cause pregnancy.

The Penis

The penis is the male organ of copulation (sexual intercourse). When erect, the stiffness of the organ allows it to penetrate into the vagina and deposit semen into the female reproductive tract.

The shaft of the penis surrounds the urethra (Figure 1). The end of the penis, called the glans penis, has a high concentration of nerve endings, resulting in very sensitive skin that influences the likelihood of ejaculation (see Figure 1). The skin from the shaft extends down over the glans and forms a collar called the prepuce (or foreskin). The foreskin also contains a dense concentration of nerve endings, and both lubricate and protect the sensitive skin of the glans penis. A surgical procedure called circumcision, often performed for religious or social reasons, removes the prepuce, typically within days of birth.

Sperm release

Sperm release involves two stages: erection and ejaculation, each of which is controlled by a separate branch of the autonomic nervous system. Erection involves parasympathetic activation causing the corpora cavernosa (sinuses that run the length of the penis) to fill with venous blood.  Erection allows the penis to be inserted into the vagina.  Ejaculation involves sympathetic activation of muscles in the penis and in the pelvic floor.  The contraction of these muscles forces sperm out of the urethra.

Testosterone

Testosterone, an androgen, is a steroid hormone produced by Leydig cells, or interstitial cells, reflects their location between the seminiferous tubules in the testes. In male embryos, testosterone is secreted by Leydig cells by the seventh week of development, with peak concentrations reached in the second trimester. This early release of testosterone results in the anatomical differentiation of the male sexual organs. In childhood, testosterone concentrations are low. They increase during puberty, activating characteristic physical changes and initiating spermatogenesis.

Functions of Testosterone

The continued presence of testosterone is necessary to keep the male reproductive system working properly, and Leydig cells produce approximately 6 to 7 mg of testosterone per day. Testosterone concentrations can be 100 times higher in the testes than in the circulation. Maintaining these normal concentrations of testosterone promotes spermatogenesis, whereas low levels of testosterone can lead to infertility. Testosterone is also released into the systemic circulation and plays an important role in muscle development, bone growth, the development of secondary sex characteristics, and maintaining libido (sex drive) in both males and females. In females, the ovaries secrete small amounts of testosterone, although most is converted to estradiol. A small amount of testosterone is also secreted by the adrenal glands in both sexes.

Part 2: Anatomy and Physiology of the Female Reproductive System

The female reproductive system functions to produce gametes and reproductive hormones; however, it also has the additional task of supporting the developing fetus and delivering it to the outside world. Unlike its male counterpart, the female reproductive system is located primarily inside the pelvic cavity (Figure 5). Recall that the ovaries are the female gonads. The gamete they produce is called an oocyte. We will discuss the production of oocytes in detail shortly. First, let’s look at some of the structures of the female reproductive system.

External Female Genitals

The external female reproductive structures are referred to collectively as the vulva. The mons pubis is a pad of fat found in both males and females that is located at the anterior, over the pubic bone. After puberty, it becomes covered in pubic hair. In females, the labia majora (labia = “lips”; majora = “larger”) are folds of hair-covered skin that begin just posterior to the mons pubis. The thinner and more pigmented labia minora (labia = “lips”; minora = “smaller”) extend medial to the labia majora. The labia minora serve to protect the female urethra and the entrance to the female reproductive tract.

The superior, anterior portions of the labia minora come together to encircle the clitoris (or glans clitoris), an organ that has abundant nerves that make it important in sexual sensation and orgasm. The hymen is a thin membrane that sometimes partially covers the entrance to the vagina. The vaginal opening is located between the opening of the urethra and the anus. It is flanked by outlets to the Bartholin’s glands (or greater vestibular glands).

Vagina

The vagina is a muscular canal (approximately 10 cm long) that serves as the entrance to the reproductive tract (Figure 5). It also serves as the exit from the uterus during menses and childbirth. The walls of the vagina are lined with an outer fibrous adventitia, a middle layer of smooth muscle, and an inner mucous membrane with transverse folds called rugae. Together, the middle and inner layers allow the expansion of the vagina to accommodate intercourse and childbirth. The Bartholin’s glands and the lesser vestibular glands (located near the clitoris) secrete mucus, which keeps the vestibular area moist.

The vagina is home to a normal population of microorganisms that help to protect against infection by pathogenic bacteria, yeast, or other organisms that can enter the vagina. Beneficial bacteria secrete lactic acid, which protects the vagina by maintaining an acidic pH (below 4.5). Lactic acid, in combination with other vaginal secretions, makes the vagina a self-cleansing organ.

Ovaries

The ovaries are the female gonads (Figure 5). These paired oval organs are each about 2 to 3 cm in length, about the size of an almond. The ovaries are located within the pelvic cavity, and are supported by ligaments.

Each ovary contains an outer cortex, housing developing oocytes, and an inner medulla, housing large blood vessels and nerves. Within the ovarian cortex, oocytes develop surrounded by supporting cells. forming an ovarian follicle. The growth and development of ovarian follicles will be described shortly.

The Ovarian Cycle

The ovarian cycle is a set of predictable changes in a female’s oocytes and ovarian follicles. During a woman’s reproductive years, it is a roughly 28-day cycle that can be correlated with, but is not the same as, the menstrual cycle (discussed shortly). The cycle includes two interrelated processes: oogenesis (the production of female gametes) and folliculogenesis (the growth and development of ovarian follicles).

1. Oogenesis: Gametogenesis in females is called oogenesis. The process begins with the ovarian stem cells, or oogonia. Oogonia form primary oocytes in the fetal ovary prior to birth. These primary oocytes are then arrested in this stage, only to resume it years later, beginning at puberty and continuing until the woman is near menopause (the cessation of a woman’s reproductive functions). The number of primary oocytes present in the ovaries declines from one to two million in an infant, to approximately 400,000 at puberty, to zero by the end of menopause.

The initiation of ovulation—the release of an oocyte from the ovary—marks the transition from puberty into reproductive maturity for women. From then on, throughout a woman’s reproductive years, ovulation occurs approximately once every 28 days, triggered by a surge of LH just prior to ovulation.

The larger amount of cytoplasm contained in the female gamete is used to supply the developing zygote with nutrients during the period between fertilization and implantation into the uterus. Interestingly, sperm contribute only DNA at fertilization, not cytoplasm. Therefore, the cytoplasm and all the cytoplasmic organelles in the developing embryo are of maternal origin. This includes mitochondria, which contain their own DNA.

2. Folliculogenesis:

Ovarian follicles are oocytes surrounded by supporting cells. They grow and develop in a process called folliculogenesis, which typically leads to ovulation of one follicle approximately every 28 days, along with death to multiple other follicles. The death of ovarian follicles is called atresia and can occur at any point during follicular development. Recall that, a female infant at birth will have one to two million oocytes within her ovarian follicles, and that this number declines throughout life until menopause, when no follicles remain.

Folliculogenesis begins with follicles in a resting state. These small primordial follicles are present in newborn females and are the prevailing follicle type in the adult ovary (Figure 6). Primordial follicles have only a single flat layer of supporting cells, called granulosa cells, that surround the oocyte, and they can stay in this resting state for years—some until right before menopause.

After puberty, a few primordial follicles will respond to a recruitment signal each day and will join a pool of immature growing follicles called primary follicles. Primary follicles start with a single layer of granulosa cells, but the granulosa cells then become active and transition from a flat or squamous shape to a rounded cuboidal shape as they increase in size and proliferate. As the granulosa cells divide, the follicles—now called secondary follicles (Figure 6)—increase in diameter, adding a new outer layer of connective tissue, blood vessels, and theca cells—cells that work with the granulosa cells to produce estrogens.

Within the growing secondary follicle, the primary oocyte now secretes a thin acellular membrane called the zona pellucida that will play a critical role in fertilization. A thick fluid, called follicular fluid, that has formed between the granulosa cells also begins to collect into one large pool, or antrum. Follicles in which the antrum has become large and fully formed are considered tertiary follicles (or antral follicles). Several follicles reach the tertiary stage at the same time, and most of these will undergo atresia. The one that does not die will continue to grow and develop until ovulation, when it will expel its secondary oocyte surrounded by several layers of granulosa cells from the ovary. Keep in mind that most follicles do not make it to this point. In fact, roughly 99 percent of the follicles in the ovary will undergo atresia..

Hormonal Control of the Ovarian Cycle

The process of development that we have just described, from primordial follicle to early tertiary follicle, takes approximately two months in humans. The final stages of development of a small cohort of tertiary follicles, ending with ovulation of a secondary oocyte, occur over a course of approximately 28 days. These changes are mostly regulated by the hormones GnRH, LH, and FSH. For more about hormonal function, refer to the Endocrine System unit.

As in men, the hypothalamus produces GnRH, a hormone that signals the anterior pituitary gland to produce the gonadotropins FSH and LH (Figure 7). These gonadotropins leave the pituitary gland and travel through the bloodstream to the ovaries, where they bind to receptors on the granulosa and theca cells of the follicles. FSH stimulates the follicles to grow (hence its name of follicle-stimulating hormone). The release of LH stimulates the granulosa and theca cells to produce the sex steroid hormone estradiol, a type of estrogen. This phase of the ovarian cycle, when the ovarian follicles are growing and secreting estrogens, is known as the follicular phase.

The more granulosa and theca cells a follicle has (that is, the larger and more developed it is), the more estrogens it will produce in response to LH stimulation. As a result of the large follicles producing large amounts of estrogens, systemic plasma estrogens concentrations increase. Following a classic negative feedback loop, these increasing concentrations of estrogens will inhibit the production of GnRH, LH, and FSH by the hypothalamus and pituitary gland. Because the large ovarian follicles require FSH to grow and survive at this point, this decline in FSH caused by negative feedback leads most of them to die (atresia). Typically, only one tertiary follicle from one ovary, now called the dominant follicle, will survive this reduction in FSH, and this follicle will be the one that releases an oocyte.

When only the one dominant follicle remains in the ovary, it again begins to secrete estrogens. It produces so much estrogen that the normal negative feedback does not occur. Instead, these extremely high concentrations of systemic plasma estrogens trigger a regulatory switch in the anterior pituitary that responds by secreting large amounts of LH and FSH into the bloodstream (Figure 7). The positive feedback loop by which more estrogens trigger release of more LH and FSH only occurs at this point in the cycle.

It is this large burst of LH (called the LH surge) which leads to ovulation of the dominant follicle. The LH surge induces many changes involving the degradation of the wall, and resulting in the expulsion of the oocyte surrounded by granulosa cells into the peritoneal cavity. This release is ovulation. In a typical 28 day cycle, ovulation occurs on day 14.

In the next section, you will follow the ovulated oocyte as it travels toward the uterus; however, there is one more important event that occurs in the ovarian cycle. The surge of LH also stimulates a change in the granulosa and theca cells that remain in the ruptured follicle after the oocyte has been ovulated. This change is called luteinization (recall that the full name of LH is luteinizing hormone), and it transforms the ruptured follicle into a new endocrine structure called the corpus luteum, a term meaning “yellowish body” (Figure 8). The luteinized granulosa and theca cells of the corpus luteum begin to produce large amounts of the sex steroid hormone progesterone, a hormone that is critical for the establishment and maintenance of pregnancy. Progesterone triggers negative feedback on the hypothalamus and pituitary gland, which keeps GnRH, LH, and FSH secretions low, so no new dominant follicles develop at this time. The corpus luteum also secretes moderate amounts of estrogens.

The post-ovulatory phase is known as the luteal phase of the ovarian cycle. If pregnancy does not occur within 10 to 12 days, the corpus luteum will stop secreting progesterone and estrogens and degrade into the corpus albicans, a nonfunctional “whitish body” that will disintegrate in the ovary over a period of several months. During this time of reduced steroid hormone secretion, FSH and LH are once again stimulated, and the follicular phase begins again with a new cohort of early ovarian follicles beginning to grow and secrete estrogens.

The Uterine Tubes

The uterine tubes (also called fallopian tubes or oviducts) serve as the conduit of the oocyte from the ovary to the uterus (Figure 8). Each of the two uterine tubes is close to, but not directly connected to, the ovary and divided into sections. The middle region of the tube, called the ampulla, is where fertilization often occurs. The uterine tubes also contain ciliated cells that beat in the direction of the uterus, producing a current that will be critical to move the oocyte.

Following ovulation, the secondary oocyte surrounded by a few granulosa cells is released into the peritoneal cavity. The nearby uterine tube, either left or right, receives the oocyte. High concentrations of estrogens that occur around the time of ovulation induce contractions of the smooth muscle along the length of the uterine tube and the result is a coordinated movement that sweeps the surface of the ovary and the pelvic cavity. Current flowing toward the uterus is generated by coordinated beating of the cilia that line the lumen of the length of the uterine tube. These cilia beat more strongly in response to the high estrogens concentrations that occur around the time of ovulation. As a result of these mechanisms, the oocyte–granulosa cell complex is pulled into the interior of the tube. Once inside, the muscular contractions and beating cilia move the oocyte slowly toward the uterus. When fertilization does occur, sperm typically meet the egg while it is still moving through the ampulla.

If the oocyte is successfully fertilized, the resulting zygote will begin to divide into two cells, then four, and so on, as it makes its way through the uterine tube and toward the uterus. If the oocyte is not fertilized, it will simply degrade—either in the uterine tube or in the uterus, where it may be shed with the next menstrual period.

The Uterus and Cervix

The uterus is the muscular organ that nourishes and supports the growing embryo (Figure 8). Its average size is approximately 5 cm wide by 7 cm long when a female is not pregnant. It has three sections. The portion of the uterus superior to the opening of the uterine tubes is called the fundus. The middle section of the uterus is called the body of uterus (or corpus). The cervix is the narrow inferior portion of the uterus that projects into the vagina. The cervix produces mucus secretions that can facilitate sperm movement through the reproductive tract. Several ligaments maintain the position of the uterus within the abdominopelvic cavity.

The wall of the uterus is made up of three layers. The most superficial layer is the serous membrane, or perimetrium, which consists of epithelial tissue that covers the exterior portion of the uterus. The middle layer, or myometrium, is a thick layer of smooth muscle responsible for uterine contractions. Most of the uterus is myometrial tissue, which allows the powerful contractions that occur during labour and the less powerful contractions (or cramps) that help to expel menstrual blood during a woman’s period.

The innermost layer of the uterus is called the endometrium. The endometrium contains a connective tissue lining, the lamina propria, which is covered by epithelial tissue that lines the lumen. Structurally, the endometrium consists of two layers: the stratum basalis and the stratum functionalis (the basal and functional layers). The stratum basalis layer is part of the lamina propria and is adjacent to the myometrium; this layer does not shed during menses. In contrast, the thicker stratum functionalis layer contains the glandular portion of the lamina propria and the endothelial tissue that lines the uterine lumen. It is the stratum functionalis that grows and thickens in response to increased levels of estrogens and progesterone. In the luteal phase of the menstrual cycle, special branches off of the uterine artery called spiral arteries supply the thickened stratum functionalis. This inner functional layer provides the proper site of implantation for the fertilized oocyte, and—should fertilization not occur—it is only the stratum functionalis layer of the endometrium that sheds during menstruation.

Recall that during the follicular phase of the ovarian cycle, the ovarian follicles are growing and secreting estrogens. At the same time, the stratum functionalis of the endometrium is thickening to prepare for a potential implantation. The post-ovulatory increase in progesterone, which characterizes the luteal phase, is key for maintaining a thick stratum functionalis. As long as a functional corpus luteum is present in the ovary, the endometrial lining is prepared for implantation. Indeed, if a blastocyst implants, signals are sent to the corpus luteum to continue secreting progesterone to maintain the endometrium, and thus maintain the pregnancy. If a blastocyst does not implant, no signal is sent to the corpus luteum and it degrades, ceasing progesterone production and ending the luteal phase. Without progesterone, the endometrium becomes thinner and, under the influence of prostaglandins, the spiral arteries of the endometrium constrict and rupture, preventing oxygenated blood from reaching the endometrial tissue. As a result, endometrial tissue dies and blood, pieces of the endometrial tissue, and white blood cells are shed through the vagina during menstruation, or the implantationmenses.

The Menstrual (Uterine) Cycle

Now that we have discussed the maturation of the cohort of ovarian follicles in the ovary, the build-up and then shedding of the endometrial lining in the uterus, and the function of the uterine tubes and vagina, we can put everything together to talk about the three phases of the menstrual (uterine) cycle—the series of changes in which the uterine lining is shed, rebuilds, and prepares for implantation.

The timing of the menstrual cycle starts with the first day of menses, referred to as day one of a woman’s period. The average length of a woman’s menstrual cycle is 28 days (typically varying from 21 to 32 days) and it is the time period used to identify the timing of events in the cycle.

Just as the hormones produced by the granulosa and theca cells of the ovary “drive” the follicular and luteal phases of the ovarian cycle, they also control the three distinct phases of the menstrual cycle. These are the menses phase, the proliferative phase, and the secretory phase.

1. Menses Phase: The menses phase of the menstrual cycle is the phase during which the endometrial lining is shed; that is, the days that the woman menstruates. Although it averages approximately five days, the menses phase can last from 2 to 7 days, or longer. The menses phase occurs during the early days of the follicular phase of the ovarian cycle, when progesterone, FSH, and LH levels are low (Figure 9). Recall that progesterone concentrations decline as a result of the degradation of the corpus luteum, marking the end of the luteal phase. This decline in progesterone triggers the shedding of the stratum functionalis of the endometrium.

2. Proliferative Phase: Once the menstrual flow ceases, the endometrium begins to proliferate again, marking the beginning of the proliferative phase of the menstrual cycle (Figure 9). It occurs when the granulosa and theca cells of the tertiary follicles begin to produce increased amounts of estrogens. These rising estrogen concentrations stimulate the endometrial lining to rebuild.

Recall that increasing estrogen concentrations leads to a decrease in FSH as a result of negative feedback, resulting in atresia of all but one of the developing tertiary follicles. The switch to positive feedback—which occurs with the elevated production of estrogens from the dominant follicle—then stimulates the LH surge that will trigger ovulation. Ovulation marks the end of the proliferative phase as well as the end of the follicular phase.

3. Secretory Phase: In addition to prompting the LH surge, high estrogen levels increase the uterine tube contractions that facilitate the pick-up and transfer of the ovulated oocyte. High estrogen levels also slightly decrease the acidity of the vagina, making it more hospitable to sperm. In the ovary, the luteinization of the granulosa cells of the ruptured follicle forms the corpus luteum, marking the beginning of the luteal phase of the ovarian cycle. In the uterus, progesterone from the corpus luteum begins the secretory phase of the menstrual cycle, in which the endometrial lining prepares for implantation (Figure 9). Over the next 10 to 12 days, the endometrial glands secrete a fluid rich in glycogen. If fertilization has occurred, this fluid will nourish the ball of cells now developing from the zygote, known as the conceptus. At the same time, the spiral arteries develop to provide blood to the thickened stratum functionalis.

If no pregnancy occurs within approximately 10 to 12 days, the corpus luteum will degrade into the corpus albicans. Levels of both estrogens and progesterone will fall, and the endometrium will grow thinner. Prostaglandins are then secreted which causes the constriction of the spiral arteries, reducing oxygen supply. The endometrial tissue will die, resulting in menses—or the first day of the next cycle.

The Breasts

Although the breasts are located far from the other female reproductive organs, they are considered accessory organs of the female reproductive system. The function of the breasts is to supply milk to an infant in a process called lactation. The external features of the breast include a nipple surrounded by a pigmented areola (Figure 10). When a baby nurses, or draws milk from the breast, the entire areolar region is taken into the mouth.

Breast milk is produced by the mammary glands, which are modified sweat glands. The milk itself exits the breast through the nipple via 15 to 20 lactiferous ducts that open on the surface of the nipple. These lactiferous ducts each extend to a lactiferous sinus that connects to a glandular lobe that contains groups of milk-secreting cells in clusters called alveoli (Figure 10). Once milk is made in the alveoli, stimulated myoepithelial cells that surround the alveoli contract to push the milk to the lactiferous sinuses. From here, the baby can draw milk through the lactiferous ducts by suckling. The non-pregnant and non-lactating female breast is composed primarily of adipose and collagenous tissue, with mammary glands making up a very minor proportion of breast volume.

Part 3: Fertilization

Fertilization occurs when a sperm and an oocyte combine and their nuclei fuse. Because each of these reproductive cells is haploid, containing half of the genetic material needed to form a human being, their combination forms a diploid cell. The resulting diploid cell, called a zygote, contains all the genetic material needed to form a human—half from the mother and half from the father.

Transit of Sperm

During ejaculation, hundreds of millions of sperm (spermatozoa) are released into the vagina. Almost immediately, millions of these sperm are overcome by the acidity of the vagina (approximately pH 3.8), and millions more may be blocked from entering the uterus by thick cervical mucus. Of those that do enter, thousands are destroyed by phagocytic uterine leukocytes. Thus, the race into the uterine tubes, which is the most typical site for sperm to encounter the oocyte, is reduced to a few thousand contenders. Their journey—thought to be facilitated by uterine contractions—usually takes from 30 minutes to 2 hours. If the sperm do not encounter an oocyte immediately, they can survive in the uterine tubes for another 3–5 days. Intercourse more than a day after ovulation is therefore unlikely to result in fertilization.

During the journey, fluids in the female reproductive tract prepare the sperm for fertilization through a process called capacitation, or priming. The fluids improve the motility of the spermatozoa and prepare them for contact with the oocyte. If sperm reach the oocyte before capacitation is complete, they will be unable to penetrate the oocyte’s thick outer protective layers.

Contact Between Sperm and Oocyte

Upon ovulation, the oocyte released by the ovary is swept into—and along—the uterine tube. Fertilization should occur in the distal uterine tube because an unfertilized oocyte cannot survive the 72-hour journey to the uterus. This oocyte (specifically a secondary oocyte) is surrounded by two protective layers. The corona radiata is an outer layer of follicular (granulosa) cells that form around a developing oocyte in the ovary and remain with it upon ovulation. The underlying zona pellucida (pellucid = “transparent”) is a transparent, but thick, glycoprotein membrane that surrounds the cell’s plasma membrane.

The oocyte encounters the surviving capacitated sperm, which stream toward it in response to chemical attractants released by the cells of the corona radiata. To reach the oocyte itself, the sperm must penetrate the two protective layers. The sperm first burrow through the cells of the corona radiata. Then, upon contact with the zona pellucida, the sperm bind to receptors in the zona pellucida. This initiates a process called the acrosomal reaction in which the enzyme-filled “cap” of the sperm, called the acrosome, releases its stored digestive enzymes. These enzymes clear a path through the zona pellucida that allows sperm to reach the oocyte. Finally, a single sperm makes contact with sperm-binding receptors on the oocyte’s plasma membrane (Figure 11). The plasma membrane of that sperm then fuses with the oocyte’s plasma membrane, and the head and mid-piece of this sperm enter the oocyte interior.

How do sperm penetrate the corona radiata? Some sperm undergo a spontaneous acrosomal reaction, which is an acrosomal reaction not triggered by contact with the zona pellucida. The digestive enzymes released by this reaction digest the extracellular matrix of the corona radiata. Thus, the first sperm to reach the oocyte is never the one to fertilize it. Rather, hundreds of sperm cells must undergo the acrosomal reaction, each helping to degrade the corona radiata and zona pellucida until a path is created to allow one sperm to contact and fuse with the plasma membrane of the oocyte.

When the first sperm fuses with the oocyte, the oocyte deploys two mechanisms to prevent polyspermy, which is penetration by more than one sperm. This is critical because if more than one sperm were to fertilize the oocyte, the resulting zygote would be a triploid organism with three sets of chromosomes. This is incompatible with life.

The first mechanism is the fast block, which involves a near instantaneous change in sodium ion permeability upon binding of the first sperm, depolarizing the oocyte plasma membrane and preventing the fusion of additional sperm cells. The fast block sets in almost immediately and lasts for about a minute, during which time an influx of calcium ions following sperm penetration triggers the second mechanism, the slow block. In this process, referred to as the cortical reaction, cortical granules sitting immediately below the oocyte plasma membrane fuse with the membrane and release certain proteins and polysaccharides into the space between the plasma membrane and the zona pellucida. The proteins cause the release of any other attached sperm and destroy the oocyte’s sperm receptors, and the mucopolysaccharides then coat the nascent zygote in an impenetrable barrier, forming a fertilization membrane.

The Zygote

Upon fertilization the two haploid nuclei derived from the sperm and oocyte decondense, expand, and replicate their DNA. The pronuclei then migrate toward each other, their nuclear envelopes disintegrate, and the male- and female-derived genetic material intermingles. This step completes the process of fertilization and results in a single-celled diploid zygote with all the genetic instructions it needs to develop into a human.

 

Part 4: Embryonic Development

Throughout this chapter, we will express embryonic and fetal ages in terms of weeks from fertilization, commonly called conception. The period of time required for full development of a fetus in utero is referred to as gestation (gestare = “to carry” or “to bear”). It can be subdivided into distinct gestational periods. A developing human is referred to as an embryo during weeks 3–8, and a fetus from the ninth week of gestation until birth. In this section, we’ll cover the embryonic stages of development, which are characterized by cell division, migration, and differentiation. By the end of the embryonic period, all the organ systems are structured in rudimentary form, although the organs themselves are either nonfunctional or only semi-functional.

Pre-implantation Embryonic Development

Following fertilization, the zygote and its associated membranes, together referred to as the conceptus, continue to be projected toward the uterus by peristalsis and beating cilia. During its journey to the uterus, the zygote undergoes five or six rapid mitotic cell divisions. Although each cleavage results in more cells, it does not increase the total volume of the conceptus (Figure 12). Each daughter cell produced by cleavage is called a blastomere (blastos = “germ,” in the sense of a seed or sprout).

Approximately 3 days after fertilization, a 16-cell conceptus reaches the uterus. The cells that had been loosely grouped are now compacted and look more like a solid mass. The name given to this structure is the morula (morula = “little mulberry”). Once inside the uterus, the conceptus floats freely for several more days. It continues to divide, creating a ball of approximately 100 cells, and consuming nutritive endometrial secretions while the uterine lining thickens. The ball of now tightly bound cells starts to secrete fluid and organize themselves around a fluid-filled cavity, the blastocoel. At this developmental stage, the conceptus is referred to as a blastocyst. Within this structure, a group of cells forms into an inner cell mass, which is fated to become the embryo. Other cells form the outer shell called trophoblasts (trophe = “to feed” or “to nourish”). These cells will develop into the chorionic sac and the fetal portion of the placenta (the organ of nutrient, waste, and gas exchange between mother and the developing offspring).

The inner mass of embryonic cells is totipotent during this stage, meaning that each cell has the potential to differentiate into any cell type in the human body. Totipotency lasts for only a few days before the cells’ fates are set as being the precursors to a specific lineage of cells.

Implantation

At the end of the first week, the blastocyst comes in contact with the uterine wall and adheres to it, embedding itself in the uterine lining via the trophoblast cells. This process is called implantation (Figure 13), which can be accompanied by minor bleeding. The blastocyst typically implants in the fundus of the uterus or on the posterior wall. However, if the endometrium is not fully developed and ready to receive the blastocyst, the blastocyst will detach and find a better spot. A significant percentage (50–75 percent) of blastocysts fail to implant; when this occurs, the blastocyst is shed with the endometrium during menses. The high rate of implantation failure is one reason why pregnancy typically requires several ovulation cycles to be achieved.

When implantation succeeds and the blastocyst adheres to the endometrium, the superficial cells of the trophoblast fuse with each other, forming the syncytiotrophoblast, a multinucleated body that digests endometrial cells to firmly secure the blastocyst to the uterine wall. In response, the uterine mucosa rebuilds itself and envelops the blastocyst (Figure 14). The trophoblast secretes human chorionic gonadotropin (hCG), a hormone that directs the corpus luteum to survive, enlarge, and continue producing progesterone and estrogens to suppress menses. These functions of hCG are necessary for creating an environment suitable for the developing embryo. As a result of this increased production, hCG accumulates in the maternal bloodstream and is excreted in the urine. Implantation is complete by the middle of the second week. Just a few days after implantation, the trophoblast has secreted enough hCG for an at-home urine pregnancy test to give a positive result.

Embryonic Membranes and Germ Layers

During the second week of development, with the embryo implanted in the uterus, cells within the blastocyst start to organize into layers. Some grow to form the extra-embryonic membranes needed to support and protect the growing embryo: the amnion, the yolk sac, the allantois, and the chorion (Figure 16).

As the third week of development begins, the two-layered disc of cells becomes a three-layered disc through the process of gastrulation, during which the cells transition from an undifferentiated to a more differentiated state. Three groups of cells, called germ layers, are formed: the endoderm, mesoderm (middle), and ectoderm. Each of these germ layers will develop into specific structures in the embryo, setting the stage for organogenesis.

Development of the Placenta

During the first several weeks of development, the cells of the endometrium—referred to as decidual cells—nourish the nascent embryo. During prenatal weeks 4–12, the developing placenta gradually takes over the role of feeding the embryo, and the decidual cells are no longer needed. The mature placenta is composed of tissues derived from the embryo, as well as maternal tissues of the endometrium. The placenta connects to the conceptus via the umbilical cord, which carries deoxygenated blood and wastes from the fetus through two umbilical arteries; nutrients and oxygen are carried from the mother to the fetus through the single umbilical vein.

The maternal portion of the placenta develops from the deepest layer of the endometrium, the decidua basalis. To form the embryonic portion of the placenta, the syncytiotrophoblast and the underlying cells of the trophoblast (cytotrophoblast cells) begin to proliferate along with a layer of extraembryonic mesoderm cells. These form the chorionic membrane, which envelops the entire conceptus as the chorion. The chorionic membrane forms finger-like structures called chorionic villi that burrow into the endometrium like tree roots, making up the fetal portion of the placenta. The cytotrophoblast cells perforate the chorionic villi, burrow farther into the endometrium, and remodel maternal blood vessels to augment maternal blood flow surrounding the villi. Meanwhile, fetal mesenchymal cells derived from the mesoderm fill the villi and differentiate into blood vessels, including the three umbilical blood vessels that connect the embryo to the developing placenta (Figure 15).

The development of the placenta, or placentation is complete by weeks 14–16. As a fully developed organ, the placenta provides nutrition and excretion, respiration, and endocrine function (Table 1 and Figure 16). It receives blood from the fetus through the umbilical arteries. Capillaries in the chorionic villi filter fetal wastes out of the blood and return clean, oxygenated blood to the fetus through the umbilical vein. Nutrients and oxygen are transferred from maternal blood surrounding the villi through the capillaries and into the fetal bloodstream.

Maternal and fetal blood do not mingle because blood cells cannot move across the placenta. This separation prevents the mother’s cytotoxic T cells from reaching and subsequently destroying the fetus, which bears “non-self” antigens.

Table 1: Functions of the Placenta

Nutrition & digestion	Respiration	Endocrine function
Mediates diffusion of maternal glucose, amino acids, fatty acids, vitamins, minerals Stores nutrients during early pregnancy to accommodate increased fetal demand later in pregnancy Excretes & filters fetal nitrogenous wastes into maternal blood	Mediates maternal-to-fetal oxygen transport Mediates fetal-to-maternal carbon dioxide transport	Secretes hCG, estrogens, and progesterone to maintain the pregnancy and stimulate maternal & fetal development Mediates transmission of maternal hormones into fetal blood Mediates transmission of fetal hormones into maternal blood

Part 5: Fetal Development

A developing human is called a fetus from the ninth week of gestation until birth. This 30-week period of development is marked by continued cell growth and differentiation, which fully develop the structures and functions of the immature organ systems formed during the embryonic period. The completion of fetal development results in a newborn who, although still immature in many ways, is capable of survival outside the womb.

 

 

 

 

 

 

 

 

 

 

The Fetal Circulatory System

During prenatal development, the fetal circulatory system is integrated with the placenta via the umbilical cord so that the fetus receives both oxygen and nutrients from the placenta. However, after childbirth, the umbilical cord is severed, and the newborn’s circulatory system must be reconfigured. Unlike a mature cardiovascular system, however, the fetal cardiovascular system also includes circulatory shortcuts, or shunts. A shunt is an anatomical (or sometimes surgical) diversion that allows blood flow to bypass immature organs such as the lungs and liver until childbirth.

The placenta provides the fetus with necessary oxygen and nutrients via the umbilical vein. (Remember that veins carry blood toward the heart. In this case, the blood flowing to the fetal heart is oxygenated because it comes from the placenta. The respiratory system is immature and cannot yet oxygenate blood on its own.)

From the umbilical vein, the oxygenated blood flows toward the inferior vena cava, all but bypassing the immature liver, via the ductus venosus shunt (Figure 18). The liver receives just a trickle of blood, which is all that it needs in its immature, semifunctional state. Blood flows from the inferior vena cava to the right atrium, mixing with fetal venous blood along the way.

Whereas the fetal liver is semi-functional, the fetal lungs are nonfunctional. The fetal circulation therefore bypasses the lungs by shifting some of the blood through the foramen ovale, a shunt that directly connects the right and left atria and avoids the pulmonary trunk altogether. Most of the rest of the blood is pumped to the right ventricle, and from there, into the pulmonary trunk, which splits into pulmonary arteries. However, a shunt within the pulmonary artery, the ductus arteriosus, diverts a portion of this blood into the aorta. This ensures that only a small volume of oxygenated blood passes through the immature pulmonary circuit, which has only minor metabolic requirements. The oxygenated blood moves through the foramen ovale into the left atrium, where it mixes with the now deoxygenated blood returning from the pulmonary circuit. This blood then moves into the left ventricle, where it is pumped into the aorta. Some of this blood moves through the coronary arteries into the myocardium, and some moves through the carotid arteries to the brain.

The descending aorta carries partially oxygenated and partially deoxygenated blood into the lower regions of the body. It eventually passes into the umbilical arteries through branches of the internal iliac arteries. The deoxygenated blood collects waste as it circulates through the fetal body and returns to the umbilical cord. Thus, the two umbilical arteries carry blood low in oxygen and high in carbon dioxide and fetal wastes. This blood is filtered through the placenta, where wastes diffuse into the maternal circulation. Oxygen and nutrients from the mother diffuse into the placenta and from there into the fetal blood, and the process repeats.

Prior to birth, the lungs are filled with amniotic fluid, mucus, and surfactant. As the fetus is squeezed through the birth canal, the fetal thoracic cavity is compressed, expelling much of this fluid. The first inhalation occurs within 10 seconds after birth and not only serves as the first inspiration, but also acts to inflate the lungs. Pulmonary surfactant is critical for inflation to occur, as it reduces the surface tension of the alveoli. A baby born prior to 26 weeks has a low chance of survival, as it produces insufficient pulmonary surfactant, and the surfaces for gas exchange have not formed adequately.

Part 6: Maternal Changes During Pregnancy, Labour, and Birth

A full-term pregnancy lasts approximately 270 days (38.5 weeks) from conception to birth. Because it is easier to remember the first day of the last menstrual period (LMP) than to estimate the date of conception, obstetricians set the due date as 284 days (approximately 40.5 weeks) from the LMP. This assumes that conception occurred on day 14 of the woman’s cycle, which is usually a good approximation. The 40 weeks of an average pregnancy are usually discussed in terms of three trimesters, each approximately 13 weeks. During the second and third trimesters, the pre-pregnancy uterus—about the size of a fist—grows dramatically to contain the fetus, causing a number of anatomical changes in the mother.

Effects of Hormones

Virtually all the effects of pregnancy can be attributed in some way to the influence of hormones—particularly estrogens, progesterone, and hCG. During weeks 7–12 from the LMP, the pregnancy hormones are primarily generated by the corpus luteum. Progesterone secreted by the corpus luteum stimulates the production of decidual cells of the endometrium that nourish the blastocyst before placentation. As the placenta develops and the corpus luteum degenerates during weeks 12–17, the placenta gradually takes over as the endocrine organ of pregnancy.

The placenta converts weak androgens secreted by the maternal and fetal adrenal glands to estrogens, which are necessary for pregnancy to progress. Estrogen levels climb throughout the pregnancy, increasing 30-fold by childbirth. Estrogens have the following actions:

• They suppress FSH and LH production, effectively preventing ovulation. (This function is the biological basis of hormonal birth control pills.)
• They induce the growth of fetal tissues and are necessary for the maturation of the fetal lungs and liver.
• They promote fetal viability by regulating progesterone production and triggering fetal synthesis of cortisol, which helps with the maturation of the lungs, liver, and endocrine organs such as the thyroid gland and adrenal gland.
• They stimulate maternal tissue growth, leading to uterine enlargement and mammary duct expansion and branching.

The placenta takes over the synthesis and secretion of progesterone throughout pregnancy as the corpus luteum degenerates. Like estrogen, progesterone suppresses FSH and LH. It also inhibits uterine contractions, protecting the fetus from preterm birth. This hormone decreases in late gestation, allowing uterine contractions to intensify and eventually progress to true labour. The placenta also produces hCG. In addition to promoting survival of the corpus luteum, hCG stimulates the male fetal gonads to secrete testosterone, which is essential for the development of the male reproductive system.

Physiology of Labour

Childbirth, or parturition, typically occurs within a week of a woman’s due date. As a pregnancy progresses into its final weeks, several physiological changes occur in response to hormones that trigger labour.

First, recall that progesterone inhibits uterine contractions throughout the first several months of pregnancy. As the pregnancy enters its seventh month, progesterone levels plateau and then drop. Estrogen levels, however, continue to rise in the maternal circulation (Figure 19). The increasing ratio of estrogen to progesterone makes the myometrium (the uterine smooth muscle) more sensitive to stimuli that promote contractions (because progesterone no longer inhibits them). Moreover, in the eighth month of pregnancy, fetal cortisol rises, which boosts estrogen secretion by the placenta and further overpowers the uterine-calming effects of progesterone.

Meanwhile, the posterior pituitary gland has been boosting its secretion of oxytocin, a hormone that stimulates the contractions of labour. At the same time, the myometrium increases its sensitivity to oxytocin by expressing more receptors for this hormone. As labour nears, oxytocin begins to stimulate stronger, more painful uterine contractions, which—in a positive feedback loop—stimulate the secretion of prostaglandins from fetal membranes. Like oxytocin, prostaglandins also enhance uterine contractile strength.

Finally, stretching of the myometrium and cervix by a full-term fetus in the vertex (head-down) position is regarded as a stimulant to uterine contractions. The sum of these changes initiates the regular contractions known as true labour, which become more powerful and more frequent with time. The pain of labour is attributed to myometrial hypoxia during uterine contractions.

Stages of Childbirth

The process of childbirth can be divided into three stages: cervical dilation, expulsion of the newborn ending with birth, and afterbirth (Figure 20).

1. Cervical Dilation: For vaginal birth to occur, the cervix must dilate fully to 10 cm in diameter—wide enough to deliver the newborn’s head. The dilation stage is the longest stage of labour and typically takes 6–12 hours.

True labour progresses in a positive feedback loop in which uterine contractions stretch the cervix, causing it to dilate and efface, or become thinner. Cervical stretching induces reflexive uterine contractions that dilate and efface the cervix further. In addition, cervical dilation boosts oxytocin secretion from the pituitary gland, which in turn triggers more powerful uterine contractions. When labour begins, uterine contractions may occur only every 3–30 minutes and last only 20–40 seconds; however, by the end of this stage, contractions may occur as frequently as every 1.5–2 minutes and last for a full minute.

2. Expulsion Stage: The expulsion stage begins when the fetal head enters the birth canal and ends with birth of the newborn. It typically takes up to 2 hours, but varies in length, depending in part on the orientation of the fetus. The most common presentation and associated with the greatest ease of vaginal birth is when the fetus faces the maternal spinal cord and the smallest part of the head (the posterior aspect called the occiput) exits the birth canal first.

Once the head is birthed, the rest of the body usually follows quickly. The umbilical cord is then double-clamped, and a cut is made between the clamps. This completes the second stage of childbirth.

3. Afterbirth: The delivery of the placenta and associated membranes, commonly referred to as the afterbirth, marks the final stage of childbirth. After expulsion of the newborn, the myometrium continues to contract. This movement shears the placenta from the back of the uterine wall. It is then easily delivered through the vagina. Continued uterine contractions then reduce blood loss from the site of the placenta.

 

Part 7: Adjustments of the Infant at Birth and Postnatal Stages

From a fetal perspective, the process of birth is a crisis. In the womb, the fetus was snuggled in a soft, warm, dark, and quiet world. The placenta provided nutrition and oxygen continuously. Suddenly, the contractions of labour and vaginal childbirth forcibly squeeze the fetus through the birth canal, limiting oxygenated blood flow during contractions and shifting the skull bones to accommodate the small space. After birth, the newborn’s system must make drastic adjustments to a world that is colder, brighter, and louder, and where he or she will experience hunger and thirst. The neonatal period (neo- = “new”; -natal = “birth”) spans the first to the thirtieth day of life outside of the uterus.

Respiratory Adjustments

Although the fetus “practices” breathing by inhaling amniotic fluid in utero, there is no air in the uterus and thus no true opportunity to breathe. (There is also no need to breathe because the placenta supplies the fetus with all the oxygenated blood it needs.) During gestation, the partially collapsed lungs are filled with amniotic fluid and exhibit very little metabolic activity. Several factors stimulate newborns to take their first breath at birth. First, labour contractions temporarily constrict umbilical blood vessels, reducing oxygenated blood flow to the fetus and elevating carbon dioxide levels in the blood. High carbon dioxide levels cause acidosis and stimulate the respiratory centre in the brain, triggering the newborn to take a breath.

The first breaths inflate the lungs to nearly full capacity and dramatically decrease lung pressure and resistance to blood flow, causing a major circulatory reconfiguration. Pulmonary alveoli open, and alveolar capillaries fill with blood. Amniotic fluid in the lungs drains or is absorbed, and the lungs immediately take over the task of the placenta, exchanging carbon dioxide for oxygen by the process of respiration.

Circulatory Adjustments

The newborn’s first breath is vital to initiate the transition from the fetal to the neonatal circulatory pattern. Inflation of the lungs decreases blood pressure throughout the pulmonary system, as well as in the right atrium and ventricle. In response to this pressure change, the flow of blood temporarily reverses direction through the foramen ovale, moving from the left to the right atrium, and blocking the shunt with two flaps of tissue. Within one year, the tissue flaps usually fuse over the shunt (Figure 21). The ductus arteriosus constricts as a result of increased oxygen concentration. Closing of the ductus arteriosus ensures that all blood pumped to the pulmonary circuit will be oxygenated by the newly functional neonatal lungs. Likewise, the ductus venosus degenerates.

Part 8: Lactation

Lactation is the process by which milk is synthesized and secreted from the mammary glands of the postpartum female breast. Breast milk provides ideal nutrition and passive immunity for the infant, encourages mild uterine contractions to return the uterus to its pre-pregnancy size (i.e., involution), and induces a substantial metabolic increase in the mother, consuming the fat reserves stored during pregnancy.

Structure of the Lactating Breast

The mammary gland is composed of milk-transporting lactiferous ducts, which expand and branch extensively during pregnancy in response to estrogens, growth hormone, cortisol, and prolactin. Moreover, in response to progesterone, clusters of breast alveoli bud from the ducts and expand outward toward the chest wall.

Breast alveoli are balloon-like structures lined with milk-secreting cuboidal cells, or lactocytes, which are surrounded by a net of contractile myoepithelial cells. Milk secreted by lactocytes fills the alveoli, and is squeezed into the ducts. Clusters of alveoli that drain to a common duct are called lobules; the lactating female has 12–20 lobules organized radially around the nipple. Milk drains from lactiferous ducts into lactiferous sinuses that meet at 4 to 18 perforations in the nipple, called nipple pores.

The Process of Lactation

The pituitary hormone prolactin is instrumental in the establishment and maintenance of breast milk supply.

Near the fifth week of pregnancy, the level of circulating prolactin begins to increase, eventually rising to approximately 10–20 times the pre-pregnancy concentration. During pregnancy, prolactin and other hormones prepare the breasts anatomically for the secretion of milk. The level of prolactin plateaus in late pregnancy, at a level high enough to initiate milk production. However, estrogen, progesterone, and other placental hormones inhibit prolactin-mediated milk synthesis during pregnancy. It is not until the placenta is expelled that this inhibition is lifted and milk production commences.

After childbirth, the baseline prolactin level drops sharply, but it is restored for a 1-hour spike during each feeding to stimulate the production of milk for the next feeding.

When the infant suckles, sensory nerve fibres in the areola trigger a neuroendocrine reflex that results in milk secretion fvia the let-down reflex (Figure 22). The posterior pituitary gland releases oxytocin, which stimulates myoepithelial cells to squeeze milk from the alveoli so it can eventually drain out through the nipples.