Chapter 28: The Reproductive Systems - Female Reproductive System

Components and Anatomy of the Female Reproductive System

The female reproductive system is composed of several specialized organs and structures that facilitate gamete production, fertilization, and fetal development. The primary reproductive organs or gonads are the paired ovaries. A series of ductal and storage structures include the uterine tubes—also known as fallopian tubes or oviducts—the uterus, and the vagina. External components of the system are collectively referred to as the vulva or pudendum. Additionally, the mammary glands of the breasts are considered part of the reproductive system due to their role in nurturing offspring. Located within the pelvic cavity, the system is situated near several key anatomical markers. The vesicouterine pouch is a pocket formed by the peritoneum between the urinary bladder and the uterus, while the rectouterine pouch, commonly known as the pouch of Douglas, is located between the uterus and the rectum. Other landmarks include the pubic symphysis, the urinary bladder, and the urethra situated anteriorly, while the sacrum and coccyx are located posteriorly.

Anatomy and Support of the Ovaries

The ovaries are paired glands that are homologous to the testes in males. They serve the dual purpose of producing gametes and secreting hormones. The gametes produced are secondary oocytes that develop into mature ova, or eggs, only after the process of fertilization. The hormones secreted by the ovaries include progesterone, estrogens, inhibin, and relaxin. To maintain their position within the pelvic cavity, the ovaries are held in place by a series of ligaments. The broad ligament is a fold of the parietal peritoneum that attaches to the ovaries by a double-layered fold called the mesovarium. The ovarian ligament serves to anchor the ovaries specifically to the uterus. The suspensory ligament attaches the ovaries to the pelvic wall and contains the ovarian blood vessels and nerves.

Histology of the Ovary

The ovary is organized into several distinct layers and structures. The germinal epithelium covers the surface, followed by the ovarian cortex and the ovarian medulla. Within the ovarian cortex are the ovarian follicles, which consist of oocytes in various stages of development. The cells surrounding the oocytes nourish them and secrete estrogens as the follicle increases in size. A mature follicle, also known as a Graafian follicle, is a large, fluid-filled structure that is ready to expel a secondary oocyte during the process of ovulation. Following ovulation, the remnants of the mature follicle transform into the corpus luteum. The corpus luteum acts as a temporary endocrine gland, producing progesterone, estrogens, relaxin, and inhibin. Eventually, the corpus luteum degenerates into a mass of fibrous tissue known as the corpus albicans. A corpus hemorrhagicum, or ruptured follicle, may contain a blood clot immediately following the discharge of a secondary oocyte into the pelvic cavity.

Oogenesis and Follicular Development

Oogenesis is the process of gamete formation within the ovaries and begins before a female is born. The process follows the same fundamental steps of meiosis as spermatogenesis but with a different timeline and outcome. During early fetal development, primordial or primitive germ cells migrate from the yolk sac to the ovaries, where they differentiate into oogonia, which are diploid ($2n$) stem cells. Before birth, a majority of these germ cells undergo a degenerative process called atresia. A small number develop into primary oocytes that enter meiosis I during fetal development but remain in a state of suspended animation. Each of these primary oocytes is surrounded by a single layer of flat follicular cells, forming a primordial follicle. At birth, a female has approximately $200,000$ to $2,000,000$ follicles. By the time of puberty, only about $40,000$ remain, and only around $400$ of these will reach full maturity and be ovulated during a woman's lifetime.

Stages of Meiosis in Oogenesis

Each month from puberty to menopause, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) stimulate the development of several primordial follicles, though usually only one reaches the stage of ovulation. The follicles progress through stages: primordial follicle to primary follicle, then to secondary follicle, and finally a mature Graafian follicle. A secondary follicle consists of theca folliculi (divided into theca externa and theca interna), a basement membrane, granulosa cells, a zona pellucida, and a fluid-filled cavity called the antrum. Surrounding the primary oocyte is the corona radiata. Just before ovulation, the diploid ($2n$) primary oocyte completes meiosis I, producing two haploid ($n$) cells of unequal size: a small first polar body that is eventually discarded and a large secondary oocyte. At ovulation, this secondary oocyte is expelled into the pelvic cavity. If fertilization does not occur, the cells degenerate. However, if a sperm cell penetrates the secondary oocyte, meiosis II resumes. The secondary oocyte then splits into two unequal haploid cells: a second polar body (also discarded) and a large ovum or mature egg. The nuclei of the sperm cell and the ovum then unite to form a diploid ($2n$) zygote.

The Uterine Tubes (Fallopian Tubes)

The uterine tubes, or oviducts, provide an essential route for sperm to reach an ovum and transport secondary oocytes or fertilized ova from the ovaries to the uterus. The tubes are divided into sections: the funnel-shaped infundibulum located near the ovary, the wider and longer ampulla, and the narrow isthmus that joins the uterus. The infundibulum ends in finger-like projections called fimbriae, which produce currents to sweep the secondary oocyte into the tube. Histologically, the uterine tubes consist of three layers. The innermost layer is the mucosa, which contains ciliated simple columnar cells acting as a "ciliary conveyor belt" to move the oocyte, and non-ciliated peg cells that provide nutrition to the ovum. The middle layer is the muscularis, responsible for peristaltic contractions that aid transport. The outer layer is the serosa.

Anatomy and Histology of the Uterus

The uterus is the site of menstruation, implantation of a fertilized ovum, and fetal development. Anatomically, it consists of the fundus (the top portion), the body, the isthmus, and the cervix, which opens into the vagina through the internal and external os. The uterine wall is composed of three layers. The perimetrium is the outer layer and part of the visceral peritoneum. The myometrium is the middle layer, consisting of $3$ layers of smooth muscle that contract in response to oxytocin released from the posterior pituitary. The innermost layer is the endometrium, which is highly vascularized. The endometrium is divided into two parts: the stratum functionalis, which lines the uterine cavity and sloughs off during menstruation, and the stratum basalis, which is permanent and gives rise to a new stratum functionalis after each menstrual cycle.

Blood Supply and Cervical Mucus

The uterus receives its blood supply from the uterine arteries, which branch from the hypogastric (internal iliac) arteries. These branch further into arcuate and radial arteries. Just before entering the endometrium, the blood vessels divide into straight arterioles, which supply the stratum basalis, and spiral arterioles, which supply the stratum functionalis. The spiral arterioles change markedly during the menstrual cycle and are integral to the shedding process. The secretory cells of the cervix mucosa produce cervical mucus, a mixture of water, glycoproteins, lipids, enzymes, and inorganic salts. Near the time of ovulation, this mucus becomes thinner and more alkaline to become more hospitable to sperm, supplementing their energy needs and protecting them from phagocytes and the generally hostile environment of the reproductive tract.

The Vagina and External Genitalia

The vagina is a fibromuscular canal extending from the body's exterior to the uterine cervix. Its mucosa is continuous with the uterine mucosa. The decomposition of glycogen within the vagina creates an acidic environment that is hostile to microbes and sperm, though alkaline components in semen help raise the pH during intercourse. The muscularis consists of two layers of smooth muscle, and the adventitia anchors the organ to adjacent structures. The hymen is a thin fold of vascularized mucous membrane that partially closes the vaginal orifice. The external genitalia, or vulva, include the mons pubis (a fatty pad cushioning the pubic symphysis), the labia majora (homologous to the scrotum), and the labia minora (homologous to the spongy urethra). The clitoris contains two small erectile bodies called corpora cavernosa and is homologous to the glans penis. The vestibule contains the external urethral orifice, vaginal orifice, and openings for vestibular glands, which secrete mucin for lubrication. The bulb of the vestibule consists of two elongated masses of erectile tissue on either side of the vaginal orifice.

The Perineum and Mammary Glands

The perineum is a diamond-shaped area medial to the thighs and buttocks in both males and females, containing the external genitalia and the anus. The mammary glands, located within the breasts, are modified sudoriferous (sweat) glands that produce milk. Each breast has a nipple with multiple openings for lactiferous ducts surrounded by a pigmented area called the areola. The mammary gland is divided into $15$ to $20$ lobes, which are further divided into lobules containing milk-secreting glands called alveoli. Milk travels from the alveoli through secondary tubules to mammary ducts, then into the lactiferous sinus for storage, and finally through the lactiferous ducts to the nipple. Suspensory ligaments of the breast, also known as Cooper's ligaments, support the breast tissue.

The Female Reproductive Cycle and Hormonal Regulation

The female reproductive cycle encompasses the ovarian cycle (events in the ovaries during and after oocyte maturation) and the uterine or menstrual cycle (changes in the endometrium to prepare for a fertilized ovum). These cycles are regulated by hormones. The hypothalamus secretes Gonadotropin-releasing hormone (GnRH), which controls the cycles by stimulating the anterior pituitary to release Follicle-stimulating hormone (FSH) and Luteinizing hormone (LH). FSH initiates follicular growth and stimulates follicles to secrete estrogens. LH stimulates further follicular development, triggers ovulation, and promotes the formation of the corpus luteum. The corpus luteum then produces progesterone, estrogens, relaxin, and inhibin.

Physiological Effects of Ovarian Hormones

Estrogens, secreted by ovarian follicles, promote the development and maintenance of reproductive structures, feminine secondary sex characteristics, and breasts. They also increase protein anabolism to promote strong bones, lower blood cholesterol, and at moderate levels, inhibit the release of GnRH, FSH, and LH. Progesterone is secreted mainly by the corpus luteum and works with estrogens to prepare and maintain the endometrium for implantation and the mammary glands for milk production. It also inhibits GnRH and LH secretion. Relaxin, produced by the corpus luteum, inhibits myometrium contractions to relax the uterus and, at the end of pregnancy, increases the flexibility of the pubic symphysis and dilates the cervix. Inhibin is secreted by granulosa cells of growing follicles and the corpus luteum to inhibit FSH and, to a lesser extent, LH.

Phases of the Reproductive Cycle: Menstrual and Pre-ovulatory

A typical reproductive cycle lasts $24$ to $35$ days, with $28$ days used as the standard model. The cycle is divided into four phases. The first phase is the Menstrual Phase (or Follicular Phase in the ovaries), consisting of roughly the first $5$ days. In the ovaries, several primordial follicles develop into primary and then secondary follicles under FSH influence. In the uterus, declining levels of estrogens and progesterone cause the release of prostaglandins that constrict spiral arterioles. This deprives the stratum functionalis of oxygen, causing it to die and slough off, leaving only the stratum basalis. The second phase is the Pre-ovulatory Phase (or Proliferative Phase in the uterus), lasting from days $6$ to $13$. A dominant follicle outgrows the others and inhibits FSH through estrogen and inhibin secretion, causing other follicles to stop growing. Fraternal twins can result if multiple follicles remain codominant. During this time, estrogens stimulate the repair of the endometrium and the proliferation of the stratum functionalis, doubling its thickness.

Phase 3: Ovulation

Ovulation typically occurs on day $14$ of a $28$ day cycle. It involves the rupture of the mature (Graafian) follicle and the release of the secondary oocyte into the pelvic cavity. This event is triggered by a positive feedback loop: high levels of estrogens from the almost mature follicle stimulate the hypothalamus and anterior pituitary to release more GnRH and LH. This resulting surge in LH concentration brings about the rupture of the follicle and the subsequent ovulation.

Phase 4: Postovulatory Phase

The Postovulatory Phase, also known as the Luteal Phase (ovary) or Secretory Phase (uterus), lasts for exactly $14$ days in a $28$ day cycle (from days $15$ to $28$). In the ovary, the collapsed mature follicle becomes the corpus luteum under LH influence, secreting progesterone, estrogen, relaxin, and inhibin. In the uterus, these hormones promote the growth and secretory activity of endometrial glands, peaking about one week after ovulation. If the oocyte is not fertilized, the corpus luteum lasts for $2$ weeks before degenerating into a corpus albicans. As hormone levels fall, negative feedback on the hypothalamus is lost, GnRH and FSH levels rise, and a new cycle begins. If fertilization occurs, the corpus luteum is maintained by Human Chorionic Gonadotropin (hCG) produced by the embryo's chorion about $8$ days after fertilization.