Female Reproductive Organs

Uterus

The uterus is a thick-walled, pear-shaped organ (see Fig. 2-2A and B) and consists of two main parts:

• The body, the expanded superior two thirds

• The cervix, the cylindrical inferior third

Figure 2–2 Female reproductive organs. A, Parts of the uterus. B, Diagrammatic frontal (coronal) section of the uterus, uterine tubes, and vagina. The ovaries are also shown. C, Enlargement of the area outlined in B. The functional layer of the endometrium is sloughed off during menstruation.

The fundus of the uterus is the rounded part of the uterine body that lies superior to the orifices of the uterine tubes. The body of the uterus narrows from the fundus to the isthmus, the constricted region between the body and the cervix (Fig. 2-2A). The lumen of the cervix, the cervical canal, has a constricted opening, the os (ostium), at each end. The internal os communicates with the cavity of the body of the uterus, whereas the external os communicates with the vagina. The walls of the body of the uterus consist of three layers:

• Perimetrium, a thin external peritoneal layer

• Myometrium, a thick smooth muscle layer

• Endometrium, a thin internal layer

At the peak of its development, the endometrium is 4 to 5 mm thick. During the luteal (secretory) phase of the menstrual cycle (see Fig. 2-8), three layers of the endometrium can be distinguished microscopically (see Fig. 2-2C) into the following:

• A compact layer, consisting of densely packed connective tissue around the neck of the uterine glands

• A spongy layer, composed of edematous connective tissue containing the dilated, tortuous bodies of the uterine glands

• A basal layer, containing the blind ends of the uterine glands

The compact and spongy layers, known collectively as the functional layer, disintegrate and are shed at menstruation and after parturition (childbirth). The basal layer of the endometrium has its own blood supply and is not cast off during menstruation.

Female External Sex Organs

The female external sex organs are known collectively as the vulva (Fig. 2-3). The labia majora, fatty external folds of skin, conceal the vaginal orifice, the opening of the vagina. Inside these labia are two smaller folds of mucous membrane, the labia minora. The clitoris, a small erectile organ, is situated at the superior junction of these folds. The vagina and urethra open into a cavity, the vestibule (the cleft between the labia minora). The vaginal orifice varies with the condition of the hymen, a fold of mucous membrane that surrounds the vaginal orifice.

Figure 2–3 External female genitalia. The labia are spread apart to show the external urethral and vaginal orifices.

Male Reproductive Organs

The male reproductive organs (see Fig. 2-1B) include the penis, testes, epididymis, ductus deferens (vas deferens), prostate, seminal glands, bulbourethral glands, ejaculatory ducts, and urethra. The two oval testes are located in the cavity of the scrotum. Each testis consists of many highly coiled seminiferous tubules that produce sperms. Immature sperms pass from the testis into a single, complexly coiled tube, the epididymis, where they are stored. From the epididymis, the ductus deferens carries the sperms to the ejaculatory duct. This duct descends into the pelvis, where it fuses with the ducts of the seminal glands to form the ejaculatory duct, which enters the urethra.

The urethra is a tube that leads from the urinary bladder through the penis to the outside of the body. Within the penis, erectile tissue surrounds the urethra. During sexual excitement, this tissue fills with blood, causing the penis to erect. Semen consists of sperms mixed with seminal fluid produced by the seminal glands, bulbourethral glands, and prostate.

Meiosis

Meiosis consists of two meiotic cell divisions (Fig. 2-6), during which the chromosome number of the germ cells is reduced to half (23, the haploid number) the number present in other cells in the body (46, the diploid number).

Figure 2–6 Diagrammatic representation of meiosis. Two chromosome pairs are shown. A to D, Stages of prophase of the first meiotic division. The homologous chromosomes approach each other and pair; each member of the pair consists of two chromatids. Observe the single crossover in one pair of chromosomes, resulting in the interchange of chromatid segments. E, Metaphase. The two members of each pair become oriented on the meiotic spindle. F, Anaphase. G, Telophase. The chromosomes migrate to opposite poles. H, Distribution of parental chromosome pairs at the end of the first meiotic division. I to K, Second meiotic division, which is similar to mitosis, except that the cells are haploid.

During the first meiotic division, the chromosome number is reduced from diploid to haploid. Homologous chromosomes (one from each parent) pair during prophase and then separate during anaphase, with one representative of each pair randomly going to each pole of the meiotic spindle. The spindle connects to the chromosome at the centromere (Fig. 2-6B). At this stage, they are double chromatid chromosomes. The X and Y chromosomes are not homologs; however, they have homologous segments at the tips of their short arms. They pair in these regions only. By the end of the first meiotic division, each new cell formed (secondary spermatocyte or secondary oocyte) has the haploid chromosome number of double chromatid chromosomes; therefore, each cell contains half the number of chromosomes of the preceding cell (primary spermatocyte or primary oocyte). This separation, or disjunction, of paired homologous chromosomes is the physical basis of segregation, or separation, of allelic genes during meiosis.

The second meiotic division follows the first division, without a normal interphase (i.e., without an intervening step of DNA replication). Each double chromatid chromosome divides, and each half, or chromatid, is randomly drawn to a different pole of the meiotic spindle; thus, the haploid number of chromosomes (23) is retained. Each daughter cell formed by meiosis has the reduced haploid number of chromosomes, with one representative of each chromosome pair (now a single chromatid chromosome).

Meiosis:

Spermatogenesis

Before puberty, primordial sperms (spermatogonia) remain dormant in the seminiferous tubules of the testes from the late fetal period. At puberty they begin to increase in number (see Fig. 2-5). After several mitotic cell divisions, the sperms grow and undergo gradual changes that transform them into primary spermatocytes—the largest germ cells in the seminiferous tubules. Each primary spermatocyte subsequently undergoes a reduction division—the first meiotic division—to form two haploid secondary spermatocytes, which are approximately half the size of primary spermatocytes. Subsequently, the secondary spermatocytes undergo a second meiotic division to form four haploid spermatids, which are approximately half the size of secondary spermatocytes. The spermatids are gradually transformed into four mature sperms during a process known as spermiogenesis. During this metamorphosis (change in form), the nucleus condenses, the acrosome forms, and most of the cytoplasm is shed and the tail forms. When spermiogenesis is complete, sperms enter the lumina (cavities) of the seminiferous tubules. The sperms then move to the epididymis (see Fig. 2-1B), where they are stored and become functionally mature. Spermatogenesis, including spermiogenesis, requires approximately 2 months for completion. Spermiogenesis normally continues throughout the reproductive life of a male.

When ejaculated, the mature sperms are free-swimming, actively motile cells consisting of a head and a tail (see Fig. 2-4A). The neck of the sperm is the junction between the head and tail. The head of the sperm, forming most of the bulk of the sperm, contains the nucleus. The anterior two thirds of the head are covered by the acrosome, a cap-like organelle containing enzymes that facilitate sperm penetration during fertilization. The tail provides the motility of the sperm, assisting with its transport to the site of fertilization in the ampulla of the uterine tube. The tail of the sperm consists of three parts: the middle piece, principal piece, and end piece. The middle piece contains the energy-producing mitochondria, which fuel the lashing movements of the tail.

Oogenesis

Oogenesis refers to the sequence of events by which oogonia (primordial oocytes) are transformed into oocytes. This maturation process begins during the fetal period, but is not completed until after puberty (see Fig. 2-5). During early fetal life oogonia proliferate by mitosis and enlarge to form primary oocytes. At birth, all primary oocytes have completed the prophase of the first meiotic division. These oocytes remain in prophase until puberty. Shortly before ovulation, a primary oocyte completes the first meiotic division (see Fig. 2-5). Unlike the corresponding stage of spermatogenesis, the division of cytoplasm is unequal. The secondary oocyte receives almost all the cytoplasm, whereas the first polar body receives very little, causing it to degenerate after a short time. At ovulation, the nucleus of the secondary oocyte begins the second meiotic division, but progresses only to metaphase.

If the secondary oocyte is fertilized by a sperm, the second meiotic division is completed and a second polar body is also formed (see Fig. 2-5). The secondary oocyte released at ovulation is surrounded by a covering of amorphous material known as the zona pellucida and a layer of follicular cells called the corona radiata (see Fig. 2-4C). The secondary oocyte is large, being just visible to the unaided eye.

Up to 2 million primary oocytes are usually present in the ovaries of a newborn infant. Most of these oocytes regress during childhood so that by puberty, no more than 40,000 remain. Of these, only approximately 400 mature into secondary oocytes and are expelled at ovulation.

Comparison of Male and Female Gametes

Compared with sperms, the oocytes are massive, immotile (see Fig. 2-4B and C), and have an abundance of cytoplasm. In terms of sex chromosome constitution, there are two kinds of normal sperms (see Fig. 2-5): 22 autosomes plus either an X sex chromosome (i.e., 23, X) or a Y sex chromosome (23, Y). There is only one kind of normal secondary oocyte: 22 autosomes plus an X sex chromosome (i.e., 23, X). The difference in sex chromosome complement forms the basis of primary sex determination.

Abnormal Gametogenesis

During gametogenesis, homologous chromosomes sometimes fail to separate—known as nondisjunction—and as a result, some gametes have 24 chromosomes and others only 22 (Fig. 2-7). If a gamete with 24 chromosomes unites with a normal one with 23 chromosomes, a zygote with 47 chromosomes results, as occurs in infants with Down syndrome (see Fig. 19-4). This condition is called trisomy 21 because of the presence of three representatives of a particular chromosome instead of the usual two. If a gamete with only 22 chromosomes unites with a normal gamete, a zygote with 45 chromosomes results. This condition is known as monosomy because only one representative of the particular chromosomal pair is present. Embryos with monosomy usually die.

Figure 2–7 Abnormal gametogenesis. The illustrations show how nondisjunction, an error in cell division, results in an abnormal chromosome distribution in gametes. Although nondisjunction of sex chromosomes is illustrated, a similar defect may occur during the division of autosomes (any chromosomes other than sex chromosomes). When nondisjunction occurs during the first meiotic division of spermatogenesis, one secondary spermatocyte contains 22 autosomes plus an X and a Y chromosome, whereas the other one contains 22 autosomes and no sex chromosome. Similarly, nondisjunction during oogenesis may give rise to an oocyte with 22 autosomes and two X chromosomes (as shown) or one with 22 autosomes and no sex chromosome.

Ovarian Cycle

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) produce cyclic changes in the ovaries (development of the ovarian follicles, ovulation, and formation of the corpus luteum), collectively known as the ovarian cycle. During each cycle, FSH promotes growth of several primary follicles (Figs. 2-8 and 2-9); however, only one of them usually develops into a mature follicle and ruptures, expelling its oocyte (Fig. 2-10).

Figure 2–9 Photomicrographs of sections from adult human ovaries. A, Light micrograph of the ovarian cortex demonstrating primordial follicles (P), which are primary oocytes surrounded by follicular cells (×270). B, Light micrograph of a secondary follicle. Observe the primary oocyte and antrum containing the follicular fluid (×132).

(From Gartner LP, Hiatt JL: Color Textbook of Histology, 2nd ed. Philadelphia, WB Saunders, 2001.)

Ovulation

The follicular cells divide actively, producing a stratified layer around the oocyte (see Fig. 2-9A and B). Subsequently, fluid-filled spaces appear around the follicular cells, which coalesce to form a single cavity, the antrum, containing follicular fluid. When the antrum forms, the ovarian follicle is called a secondary follicle (see Fig. 2-9B). The primary oocyte is surrounded by follicular cells, called the cumulus oophorus, which projects into the enlarged antrum. The follicle continues to enlarge and soon forms a bulge on the surface of the ovary (Fig. 2-10A). A small, oval, avascular spot, the stigma, soon appears on this bulge. Before ovulation, the secondary oocyte and some cells of the cumulus oophorus detach from the interior of the distended follicle (see Fig. 2-10B).

Figure 2–10 Diagrams (A–D) illustrating ovulation. When the stigma ruptures, the secondary oocyte is expelled from the ovarian follicle with the follicular fluid. After ovulation, the wall of the follicle collapses.

Ovulation follows within 24 hours of a surge of LH production that appears to be the result of signaling molecules from the granulosa cells. This surge, elicited by the high estrogen level in blood (Fig. 2-11), appears to cause the stigma to rupture, expelling the secondary oocyte along with the follicular fluid (see Fig. 2-10D). Plasmins and matrix metalloproteinases also appear to have some control over stigma rupture.

Figure 2–11 Blood levels of various hormones during the menstrual cycle. Follicle-stimulating hormone (FSH) stimulates the ovarian follicles to develop and produce estrogens. The level of estrogens rises to a peak just before the luteinizing hormone (LH) surge induces ovulation. Ovulation normally occurs within 24 hours after the LH surge. If fertilization does not occur, the blood levels of circulating estrogens and progesterone fall. This hormone withdrawal causes the endometrium to regress and menstruation to start again.

The expelled secondary oocyte is surrounded by the zona pellucida, an acellular glycoprotein coat, and one or more layers of follicular cells, which are radially arranged to form the corona radiata (see Fig. 2-4C) and the cumulus oophorus.

Mittelschmerz and Ovulation

A variable amount of abdominal pain, called mittelschmerz, accompanies ovulation in some women. Mittelschmerz may be used as a sign of ovulation; however, there are better indicators, such as the slight drop in basal body temperature, followed by a sustained rise after ovulation.

Anovulation and Hormones

Some women do not ovulate because of an inadequate release of gonadotropins. In some of these women, ovulation can be induced by the administration of gonadotropins or an ovulatory agent, resulting in maturation of several ovarian follicles and multiple ovulations. The incidence of multiple pregnancy increases when ovulation is induced.

Anovulatory Menstrual Cycles

In anovulatory cycles, the endometrial changes are minimal; the proliferative endometrium develops as usual, but no ovulation occurs and no corpus luteum forms. Consequently, the endometrium does not progress to the luteal phase; it remains in the proliferative phase until menstruation begins. The estrogen in oral contraceptives, with or without progesterone, suppresses ovulation by acting on the hypothalamus and pituitary gland, inhibiting secretion of gonadotropin-releasing hormone, follicle-stimulating hormone, and luteinizing hormone.

Menstrual Cycle

The menstrual cycle is the period during which the oocyte matures, is ovulated, and enters the uterine tube (Fig. 2-11). Estrogen and progesterone produced by the ovarian follicles and the corpus luteum cause cyclic changes in the endometrium of the uterus. These monthly changes in the uterine lining constitute the menstrual cycle. The average menstrual cycle is 28 days (ranging from 23 to 35 days). Day 1 of the cycle corresponds to the day on which menstruation begins.

Oocyte Transport

During ovulation, the fimbriated (fringed) end of the uterine tube comes in close proximity to the ovary (see Fig. 2-10). The fingerlike processes of the tube, the fimbriae, move back and forth over the ovary. The sweeping action of the fimbriae and the fluid currents produced by them “sweep” the secondary oocyte into the funnel-shaped infundibulum of the tube (see Fig. 2-2B). The oocyte then passes into the ampulla of the tube, primarily as a result of waves of peristalsis—movements of the wall of the tube characterized by alternate contraction and relaxation.

Sperm Transport

During ejaculation, sperms are rapidly transported, from their storage site in the epididymis (see Fig. 2-1B) to the urethra by peristaltic contractions of the ductus deferens. Secretions from the seminal glands, prostate, and bulbourethral glands and the sperms form the semen (ejaculate). The number of sperms ejaculated ranges from 200 to 600 million. The sperms pass slowly through the cervical canal by movements of their tails. Vesiculase, an enzyme produced by the seminal glands, coagulates some of the semen and forms a vaginal plug that may prevent backflow of semen into the vagina. At the time of ovulation, the amount of cervical mucus increases and becomes less viscid, making it more favorable for sperm transport. Prostaglandins in the semen stimulate uterine motility and help to move the sperms through the uterus to the site of fertilization in the uterine tube.

The sperms move 2 to 3 mm per minute. They move slowly in the acid environment of the vagina, but more rapidly in the alkaline environment of the uterus. Approximately 200 sperms reach the fertilization site in the uterine tube.