Anatomy and Physiology

• The infundibulum is a funnel‐shaped region of the uterine tube that bears fingerlike projections called fimbriae. Pulsating cilia on the fimbriae draw the secondary oocyte into the uterine tube.

• The ampulla is the widest and longest region of the uterine tube. Fertilization of the oocyte by a sperm usually occurs here.

• The isthmus is a narrow region of the uterine tube whose terminus enters the uterus.

       The wall of the uterine tube consists of the following three layers:

• The serosa, a serous membrane, lines the outside of the uterine tube.

• The middle muscularis consists of two layers of smooth muscle that generate peristaltic contractions that help propel the oocyte forward.

• The inner mucosa consists of ciliated columnar epithelial cells that help propel the oocyte forward, and secretory cells that lubricate the tube and nourish the oocyte.

• The uterus (womb) is a hollow organ within which fetal development occurs. The uterus is characterized by the following regions:

• The fundus is the upper region where the uterine ducts join the uterus.

• The body is the major, central portion of the uterus.

• The isthmus is the lower, narrow portion of the uterus.

• The cervix is a narrow region at the bottom of the uterus that leads to the vagina. The inside of the cervix, or cervical canal, opens to the uterus above through the internal os and to the vagina below through the external os. Cervical mucus secreted by the mucosa layer of the cervical canal serves to protect against bacteria entering the uterus from the vagina. If an oocyte is available for fertilization, the mucus becomes thin and slightly alkaline. These are attributes that promote the passage of sperm. At other times, the mucus is viscous and impedes the passage of sperm.

The uterus is held in place by the following ligaments:

• The middle muscularis consists of two layers of smooth muscle that permit expansion of the vagina during childbirth and when the penis is inserted.

• The inner mucosa has no glands. But bacterial action on glycogen stored in these cells produces an acid solution that lubricates the vagina and protects it against microbial infection. The acidic environment is also inhospitable to sperm. The mucosa bears transverse ridges called rugae.

• The vulvae (pudendum) make up the external genitalia. The following structures are included:

• The mons pubis is a region of adipose tissue above the vagina that is covered with hair.

• The labia majora are two folds of adipose tissue that border each side of the vagina. Hair and sebaceous and sudoriferous glands are present. Developmentally, the labia majora are analogous to the male scrotum.

• The labia minora are smaller folds of skin that lie inside the labia majora.

• The vestibule is the recess formed by the labia minora. It encloses the vaginal orifice, the urethral opening, and ducts from the greater vestibular glands whose mucus secretions lubricate the vestibule.

• The clitoris is a small mass of erectile and nervous tissue located above the vestibule. Extensions of the labia minora join to form the prepuce of the clitoris, a fold of skin covering the clitoris.

Figure 1. View of the female reproductive system.

Mammary glands

The mammary glands are sudoriferous (sweat) glands specialized for the production of milk. The milk‐producing secretory cells form walls of bulb‐shaped chambers called alveoli that join together with ducts, in grapelike fashion, to form clusters called lobules. Numerous lobules assemble to form a lobe. Each breast contains a single mammary gland consisting of 15 to 20 of these lobes. Lactiferous ducts leading away from the lobes widen into lactiferous sinuses that serve as temporary reservoirs for milk. The ducts narrow again as they lead through a protruding nipple. The nipple, whose texture is made coarse by the presence of sebaceous glands, is surrounded by a ring of pigmented skin called the areola. Contraction of myoepithelial cells surrounding the alveoli force milk toward the nipples.

The breasts begin to enlarge in females at the onset of puberty. Proliferating adipose (fat) tissue expands the breast, while suspensory ligaments attached to the underlying fascia provide support. In nonpregnant females (and in males), the glands and ducts are not fully developed.

During pregnancy, estrogen and progesterone stimulate extensive development of the mammary glands and associated ducts. After childbirth, various hormones, especially prolactin from the anterior pituitary, initiate lactation, or milk production. When neurons are stimulated by the sucking of an infant, nerve impulses activate the posterior pituitary to secrete oxytocin, which in turn stimulates contraction of the myoepithelial cells surrounding the alveoli. Milk is then forced toward the nipple (the letdown reflex).

Oogenesis

Oogenesis consists of the meiotic cell divisions that lead to the production of ova (eggs) in females. The process begins during fetal development with the fetal ovary. Diploid cells called oogonia divide by mitosis and differentiate to produce primary oocytes (still diploid with 46 chromosomes). Each primary oocyte is encircled by one or more layers of cells. The oocyte and encircling cells together are called an ovarian follicle. The primary oocytes (within their follicles) begin meiosis, but division progresses only to prophase I. They remain at this stage until puberty.

The following stages in the development of an ovarian follicle are observed:

1. The primordial follicle, the initial fetal state of the follicle, encircles the oocyte with a single layer of cells, called follicular cells.

2. The primary follicle, the next stage of follicular development, possesses two or more layers of encircling cells, now called granulosa cells.

3. The secondary follicle is distinguished by the presence of the antrum, a fluid‐filled, central cavity.

4. In a mature (vesicular, or Graafian) follicle, the primary oocyte has completed meiosis I. It is the stage of follicular development that precedes ejection of the oocyte from the ovary (ovulation). The following features are observed:

5. The zona pellucida, a clear layer of glycoprotein, surrounds the oocyte.

6. The corona radiata, a ring of granulosa cells, encircles the zona pellucida.

7. Several layers of cells (theca cells) surround the granulosa cells.

8. The corpus luteum is the remains of the follicle following ovulation. It remains functional, producing estrogen, progesterone, and inhibin, until it finally degenerates.

During each menstrual cycle, one primary oocyte, enclosed in its follicle, resumes meiosis I to produce two daughter cells (each haploid with 23 chromosomes). One daughter cell, the secondary oocyte, contains most of the cytoplasm, ensuring that adequate amounts of stored food, as well as mitochondria, ribosomes, and other cytoplasmic organelles, will be available for the developing embryo. The other daughter cell, a first polar body, is much smaller and contains little cytoplasm and few if any organelles. The secondary oocyte then begins meiosis II (equatorial division) but again stops at prophase (this time prophase II). The first polar body may also begin meiosis II, but it will eventually degenerate.

Ovulation occurs when a secondary oocyte and its first polar body, surrounded by the zona pellucida and corona radiata, rupture from their mature follicle and are expelled from the surface of the ovary. The oocyte is then swept up into the uterine (fallopian) tube and advances toward the uterus. If a sperm cell penetrates the corona radiata and zona pellucida and enters the secondary oocytes, meiosis II resumes in the secondary oocytes, producing an ovum and a second polar body. If a first polar body is present, it too, may resume meiosis II, producing daughter polar bodies. Fertilization occurs when the nuclei of the sperm cell and ovum unite, forming a zygote (fertilized egg). Any polar bodies present ultimately degenerate.

Hormonal regulation of oogenesis and the menstrual cycle

The human female reproductive cycle is characterized by events in the ovary (ovarian cycle) and the uterus (menstrual cycle). The purpose of these cycles is to produce an egg and to prepare the uterus for the implantation of the egg, should it become fertilized. The ovarian cycle consists of three phases:

1. The follicular phase describes the development of the follicle, the meiotic stages of division leading to the formation of the secondary oocytes, and the secretion of estrogen from the follicle.

2. Ovulation, occurring at midcycle, is the ejection of the egg from the ovary.

3. The luteal phase describes the secretion of estrogen and progesterone from the corps luteum (previously the follicle) after ovulation.

The menstrual (uterine) cycle consists of three phases:

1. The proliferative phase describes the thickening of the endometrium of the uterus, replacing tissues that were lost during the previous menstrual cycle.

2. The secretory phase follows ovulation and describes further thickening and vascularization of the endometrium in preparation for the implantation of a fertilized egg.

3. The menstrual phase (menstruation, menses) describes the shedding of the endometrium when implantation does not occur.

The activities of the ovary and the uterus are coordinated by negative‐ and positive‐feedback responses involving gonadotropin releasing hormone (GnRH) from the hypothalamus, follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary, and the hormones estrogen and progesterone from the follicle and corpus luteum. A description of the events follows):

1. The hypothalamus and anterior pituitary initiate the reproductive cycle: The hypothalamus monitors the levels of estrogen and progesterone in the blood. In a negative‐feedback fashion, low levels of these hormones stimulate the hypothalamus to secrete GnRH, which in turn stimulates the anterior pituitary to secrete FSH and LH.

2. The follicle develops: FSH stimulates the development of the follicle from primary through mature stages.

3. The follicle secretes estrogen: LH stimulates the cells of the theca interna and the granulosa cells of the follicle to secrete estrogen. Inhibin is also secreted by the granulosa cells.

4. Ovulation occurs: Positive feedback from rising levels of estrogen stimulate the anterior pituitary (through GnRH from the hypothalamus) to produce a sudden midcycle surge of LH. This high level of LH stimulates meiosis in the primary oocyte to progress toward prophase II and triggers ovulation.

5. The corpus luteum secretes estrogen and progesterone: After ovulation, the follicle, now transformed into the corpus luteum, continues to develop under the influence of LH and secretes both estrogen and progesterone.

6. The endometrium thickens: Estrogen and progesterone stimulate the development of the endometrium, the inside lining of the uterus. It thickens with nutrient‐rich tissue and blood vessels in preparation for the implantation of a fertilized egg.

7. The hypothalamus and anterior pituitary terminate the reproductive cycle: Negative feedback from the high levels of estrogen and progesterone cause the anterior pituitary (through the hypothalamus) to abate the production of FSH and LH. Inhibin also suppresses production of FSH and LH.

8. The endometrium either disintegrates or is maintained, depending on whether implantation of the fertilized egg occurs, as follows:

• Implantation does not occur: In the absence of FSH and LH, the corpus luteum deteriorates. As a result, estrogen and progesterone production stops. Without estrogen and progesterone, growth of the endometrium is no longer supported, and it disintegrates, sloughing off during menstruation.

• Implantation occurs: The implanted embryo secretes human chorionic gonadotropin (hCG) to sustain the corpus luteum. The corpus luteum continues to produce estrogen and progesterone, maintaining the endometrium. (Pregnancy tests check for the presence of hCG in the urine.)

In addition to influencing the reproductive cycle, estrogen stimulates the development of secondary sex characteristics in females. These include the distribution of adipose tissue (to the breasts, hips, and mons pubis), bone development leading to a broadening of the pelvis, changes in voice quality, and growth of various body hair.

Figure 2. The female reproductive cycle broken down by days.