Overview – The Female Reproductive System
Plate 18-1. The Ovary
Plate 18-2. The Ovary: Primary And Secondary Follicles
Plate 18-3. The Ovary: The Tertiary Follicle
Plate 18-4. The Oviduct
Plate 18-5. The Uterus
The female reproductive system performs a number of important functions. First, it produces the egg, or Ovum, and provides for its maturation. Second, it places the mature egg so that it is available for fertilization by incoming spermatozoa. Third, it provides a warm, safe, secure, and nutritious environment in which the fertilized egg can grow and develop. Fourth, the female reproductive system is an integral part of the endocrine system.
The female reproductive system accomplishes these life-giving acts with three major organs: the Ovary, the Oviduct, and the Uterus. These organs, each of which has several histologic subdivisions, are packaged into a compact and efficient system. Figure 18-1 shows the major components of the female reproductive system. The Ovary at left is seen in surface view; the one at right is shown in longitudinal section to reveal the developing follicles within. Close by the ovaries lie the paired oviducts. The Oviduct – also called the Uterine Tube or Fallopian Tube – receives the egg when it is ovulated, or released from the Ovary, and moves the egg through its lumen toward the Uterus. Normally, when fertilization occurs, it takes place in the Oviduct. The fertilized egg is then transported to the Uterus, where it is implanted. Once Implantation has occurred, human development continues at a rapid rate, and the Uterus undergoes a dramatic increase in size as the baby grows. At term, the baby is pushed through the vaginal canal by uterine contractions and enters the “outside world.”
Human life begins with the union of two cells, a sperm and an egg. The sperm and egg must first be produced by two adults of the species. The preceding chapter on the male reproductive system began by illustrating the Testis, the organ of sperm production. This chapter begins by illustrating the Ovary, the organ of egg production.
The human female is born with about 400,000 primordial germ cells that can develop into egg cells, or oocytes. Of these, only about 450 are ovulated (at the rate of one per month for some 35 to 40 years) and made available for fertilization. The transition from early germ cell to mature Oocyte is dramatic, and much of that transition occurs within the cortex of the Ovary itself. The Oocyte – a large, round cell that serves as a repository for genetic material and contains many of the cytoplasmic components necessary for early development – cannot grow alone. To undergo its maturation, the Oocyte requires assistance from other cells. Consequently, each Oocyte and its helper cells are organized into a functional unit called a Follicle. The structure and function of the ovarian Follicle change dramatically during the process of Oocyte maturation. Some of these changes are illustrated in the first three plates of this chapter.
Plate 18-1 at right is a low-magnification light micrograph of a section taken through the Ovary of the monkey. The Ovary is a large, almond-shaped structure, measuring about 5 cm long, 2 cm wide, and 1 cm thick. Because of its large size, only a small portion of the Ovary can be shown in a single photo micrograph. In the plate, part of the lateral margin of the Ovary is covered by a simple Cuboidal Epithelium known as the germinal epithelium (GE). The name is unfortunate because it incorrectly implies that the epithelium participates in germ cell formation. However, the Germinal Epithelium actually is a continuation of the layer of cells that lines the peritoneal cavity. Beneath the Germinal Epithelium lies a tough connective tissue coat, the Tunica Albuginea (TA). The tunical albuginea outlines the outer part of the Ovary, the cortex, in which the developing follicles lie. The core of the Ovary, called the Medulla (M), is made up of connective tissue through which blood vessels (V) pass.
Several follicles in different stages of development are evident in Plate 18-1. Numerous primary follicles (PF) are clustered at the periphery of the cortex near the Tunica Albuginea. Each primary Follicle consists of a central Oocyte (*) surrounded by a single layer of cuboidal epithelial cells. Each of these epithelial cells is called a follicular cell (or Follicle cell). As the Follicle develops, the Oocyte increases in size, and the follicular cells multiply by Mitosis. Soon, the primary Follicle has enlarged to become a secondary Follicle (SF), an Oocytesurrounded by several layers of Follicular Cells. When the Follicular Cells become arranged in layers, they are known by a new name – granulosa cells. Compare the images of primary follicles and secondary follicles in the photomicrograph at right for a visual image of their microanatomy.
Plate 18-1, Light micrograph of section through part of the Ovary of the squirrel monkey. C, cortex; CT, connective tissue in the Medulla; GE, Germinal Epithelium that covers the Ovary; M, Medulla; PF, primary Follicle; SF, secondary Follicle; TA, Tunica Albuginea; V, blood vessel in Medulla; *, Oocyte. 325 X
The follicles present in the ovaries of a newborn female are called primordial follicles. A primordial Follicle consists of an Oocyte surrounded by a monolayer of squamous epithelial cells. Under appropriate conditions of hormonal stimulation, which normally occur at puberty, the primordial follicles become activated and start to grow. The Oocyte enlarges, and the squamous cells that surround it swell and become cuboidal. These structural changes herald the transformation of a primordial Follicle into a primary Follicle. The primary Follicle, then, consists of an Oocyte surrounded by a single layer of plump cuboidal Follicle cells.
Several primary follicles are illustrated in the lowmagnification electron micrograph in Figure A. Here, the Oocyte (O) appears as a large, spherical, pale cell with its Nucleus (N) set slightly off-center. The Oocyte is surrounded by a monolayer of cuboidal Follicle cells (F). The Follicle cells, in turn, are surrounded by a sheath consisting of several layers of flattened connective tissue cells (C). It is important to understand the relative positions of these three elements of the ovarian Follicle, for they provide the building blocks for future follicular development.
During the course of normal follicular development, the Oocyte will grow, the Follicle cells will multiply by Mitosis to form a population of granulosa cells, and the connective tissue will become a complex, extensive sheath called the Thecafolliculi.
Some of these changes are apparent in Figure B, a low-magnification electron micrograph of a secondary Follicle. When primary follicles continue to grow, the Oocyte enlarges considerably. While this enlargement is apparent, it is nowhere as obvious as in the dramatic changes displayed by the Follicle cells. In the secondary Follicle shown at right the number of Follicular Cells has greatly increased, forming a large, stratified population of granulosa cells (G) around the Oocyte (O).
The granulosa cells secrete fluid, often called follicular fluid (or Liquor Folliculi), that is initially secreted into spaces between the adjacent granulosa cells (*). Eventually, these spaces fuse, and the Follicular Fluid becomes contained within a single large cavity called the Antrum. An Antrum (A) at an early stage of formation is evident in Figure B. Meanwhile, the connective tissue cells in the sheath around the granulosa cells have multiplied, secreted considerable amounts of Collagen, and are now known as the Theca folliculi (T). The Theca folliculi is divided into two portions – an inner, highly cellular region, called the Thecainterna, and an outer, more fibrous region, the Theca externa. Whereas no visible boundary exists between the Theca interna and the Theca externa, a distinct boundary – in the form of a Basement Membrane – separates the granulosa cells from the Theca interna. The position of the basement membrane is outlined by the dotted line in Figure B.
Figure B shows a region of medium electron density that surrounds the Oocyte. This Polysaccharide-rich coat is the Zona Pellucida (Z). The Zona Pellucida is invaded by cytoplasmic extensions from the granulosa cells and by Microvilli from the Oocyte. At the time of ovulation, when the Follicle ruptures and the egg is released, the Oocyte is still surrounded by the Zona Pellucida and a coating of granulosa cells. These accompany the Oocyte on its journey down the Oviduct.
Figure A. Electron micrograph of part of the cortex of the Ovary of the mouse containing several primary follicles. C, connective tissue cells; F, Follicle cells; N, Nucleus of Oocyte; O, Oocyte; S, Steroid-secreting cells in the ovarian stroma. 2,050 X
Plate 18-2, Figure B. Electron micrograph of a secondary Follicle within the Ovary of the cat. A, Antrum; G, granulosa cells; O, Oocyte; T, Theca folliculi; Z, Zona Pellucida; *, fluid-filled spaces between granulosa cells; dotted line, boundary between granulosa cells and Theca interna. 850 X
The Ovary: The Tertiary Follicle
After Menarche, when menstruation begins, some of the secondary follicles in the Ovary continue to develop and become tertiary follicles. Tertiary follicles are quite large and have a well-developed, fluidfilled cavity, the Antrum. In humans, one of the several tertiary follicles will continue to grow and develop into a mature Follicle, called the Graafian Follicle. It is the Graafian Follicle that releases the Oocyte into the Oviduct for fertilization.
Figures A and B at right are a matched pair of light and electron micrographs through an early tertiary Follicle. (Classifications of follicular development vary in different texts. Some sources call the structure at right a late secondary Follicle; others call it a growing Follicle.) In this particular Follicle, the Antrum (A) is well developed, constituting the bulk of the follicular volume. In a mature Follicle, the Antrum would be continuous; here, it is still traversed by a column of granulosa cells (G’) that will eventually move to occupy a peripheral location. The Oocyte(O), now surrounded by a prominent Zona Pellucida (arrow), is situated off to one side. A cloud of granulosa cells, called the cumulus oophorus (CO), surrounds the Oocyte. The granulosa cells that touch the Oocyte have a special name, the Corona Radiata. The cells that form the Corona Radiata stick tightly to the Oocyte and are shed with it at ovulation, forming a noticeable halo. When the sperm arrives to fertilize the ovulated Oocyte, it first encounters the Corona Radiata, then the Zona Pellucida, before it makes contact with the Plasma membrane of the egg cell itself.
Granulosa cells (G) line the Antrum and occupy a peripheral location within the tertiary Follicle. They sit atop a Basement Membrane, too small to be seen at this low magnification. The Basement Membrane separates the granulosa cells from the outer sheath of the Follicle, the Theca folliculi. As described in the previous plate, the Theca folliculi has two structurally and functionally distinct regions: the highly cellular Theca interna (TI), which has endocrine functions, and the more fibrous Theca externa (TE), which does not. Close examination of Figures A and B will reveal these regions; they are, to be sure, more conspicuous when viewed by electron microscopy (Figure B).
The cells of the Theca interna (TI) in Figure B contain large inclusions that look like lipid droplets. These inclusions contain Steroid hormones and indicate that the cells of the Theca interna are endocrine cells. At this stage, the cells of the Thecainterna make an Estrogen precursor, a Steroid molecule called androstene dione. Androstene dione is converted by the granulosa cells within the Follicle to form Estradiol, the most potent of all natural estrogens. After ovulation, the function of these cells changes; they become the Theca lutein cells of the Corpus Luteum and secrete large amounts of Progesterone. Shortly after the egg is released from the mature Graafian Follicle, the entire Follicle undergoes a drastic change in structure and function. Instead of being a Follicle that supports the development of the egg, it becomes the Corpus Luteum, an endocrine organ, that secretes Progesterone, which prevents maturation and ovulation in other follicles. If the Oocyte is fertilized, the Corpus Luteum persists; if not, it degenerates, and the cycle of follicular development and ovulation begins a new.
plate 18-3, Figures A and B. Matched pair of light and electron micrographs of serial sections taken through an early tertiary Follicle of the mouse Ovary. A, Antrum; CO, Cumulus Oophorus; G, granulosa cells; G’, column of granulosa cells that traverse Antrum; O, Oocyte; N, Nucleus of Oocyte; TE, Theca externa; TI, Theca interna; V, blood vessel; arrow, Zona Pellucida. Figure A, 350 X; Figure B, 600 X
The Oviduct is a long, slender, musculomembraneous tube that carries the Ovum from its origin in the Ovary to its destination in the Uterus. The Oviduct has three major interrelated functions. First, it must pick up the egg at the moment of its expulsion from the Ovary. This is no mean feat, since the Ovary and Oviduct are not directly attached to one another (see Figure 18-1). Second, it must transport and nourish the egg on its journey to the Uterus. Third, it must provide a suitable environment for fertilization of the egg by a single Spermatozoon.
The microanatomy of the Oviduct is directly related to its function. The Oviduct is a complex conduit that is ensheathed by layers of muscle that move the egg. In addition, it is lined by an epithelium that provides a suitable fluid environment not only for the egg, but also for the sperm that fertilizes it. Figures A and B are a matched pair of light and electron micrographs of the wall of the monkey Oviduct. The epithelium that lines the Oviduct is a simple Columnar Epithelium that contains ciliated cells (C) and secretory cells (S). The secretory cells are easily identified in Figure B by the large number of small, electron-dense Secretory Granules present in the apical Cytoplasm. Here, some of the granules just released from the cells are evident in the lumen (L) of the Oviduct. The secretory product of these cells forms a viscous fluid that fills the lumen and, in so doing, covers and lubricates the epithelial surface. The fluid is moved toward the Uterus not only by the metachronal beating of the cilia of the ciliated cells, but also by the muscular contractions of the Smooth Muscle in the muscularis (M) upon which the Mucosarests.
The Mucosa of the Oviduct consists of the epithelium described above and a thin Lamina Propria (LP) made up of loose connective tissue. Unlike other tubes in the body, such as the gut, the Oviduct‘s Mucosa does not contain a Muscularis Mucosae. In addition, it has no Submucosa. Instead, the Mucosa – consisting of the epithelium and Lamina Propria – rests directly on the muscle layers, collectively called the muscularis. The histologic arrangement of the epithelium, Lamina Propria and muscularis (M) is readily apparent in Figures A and B at right. The Mucosa is thrown into an extensive series of branched folds called Folia. Portions of several Folia (F) are evident in the micrographs at right. As in the Villus of the intestine, the core of each folium is composed of the Lamina Propria.
The Oviduct, which is some 12 cm long and about twice the diameter of an earthworm, contains four different regions. The distal portion, near the Ovary, is called the Infundibulum. The Infundibulum leads to the Ampulla, the area from which Figures A and B were made. The Ampulla leads to a constricted region called the Isthmus. The Isthmus in turn, enters the Uterus. The part of the Oviductthat crosses the uterine wall is called the pars interstitialis. The Folia are most extensive, and the epithelium most well-developed, in the distal portions of the Oviduct. As the Oviduct nears the Uterus, the Folia become shorter and flatter, and the epithelium decreases in height.
The microanatomy of the Oviduct is greatly influenced by the woman’s hormonal status; it will display different structural profiles at different stages of the menstrual cycle. In patients in whom ovariectomy has been performed, for example, the epithelium atrophies. The secretory cells become small and inactive; most of the ciliated cells shed their cilia. Under conditions of hormone replacement with Estradiol, however, the epithelium rapidly resumes the condition depicted at right; the ciliated cells regrow their cilia, and the secretory cells become active once again.
Plate 18-4, Figures A and B. Matched pair of light and electron micrographs of the Oviduct of the squirrel monkey. C, ciliated cell; F, folium; L, lumen; LP, Lamina Propria; M, muscularis; S, secretory cells. Figure A, 500 X; Figure B, 1,000 X
After the Oocyte has been released from the Ovary, it travels down the Oviduct. If fertilization occurs, cleavage of the fertilized egg, or Zygote, follows, and the resultant ball of cells, the morula, travels through the Oviduct and into the Uterus. There, Implantation occurs, and the Blastocyst – the very early embryo – begins to grow.
The Uterus is an extremely important organ, for it not only permits attachment and Implantation of the Blastocyst, but it also establishes a nutritional organ, called the Placenta, for the developing fetus. The Mucosa that lines the inner surface of the Uterus, called the Endometrium, is primed to receive the fertilized egg when ovulation occurs. If fertilization takes place and Implantation follows, the Uterusbecomes the site of embryonic and fetal development. If fertilization and Implantation do not occur, however, the Uterus abandons its state of readiness and sloughs most of its endometrial lining at menstruation. When a new cycle of follicular maturation in the Ovary begins, the Uterus renews its lining to prepare for another cycle of ovulation, potential fertilization, and Implantation.
Part of the wall of the human Uterus is shown at very low magnification by light microscopy in Figure A. The wall of the Uterus has the same basic components as the wall of the Oviduct described in the previous plate, although the names are different. The Mucosa lining the Uterus, called the Endometrium (ENDO), consists of a simple Columnar Epithelium that rests on a highly cellular bed of connective tissue. As in the Oviduct, no muscularis mucosae or Submucosa is present; consequently, the muscularis, here called the Myometrium (MYO), is situated directly beneath the Endometrium. The outer surface of the Uterus, not shown here, is covered by a serosal layer (continuous with the peritoneum lining the body cavity) called the Perimetrium.
The epithelium (EP) that lines the inner uterine wall frequently dives into the underlying connective tissue to form numerous simple tubular Endometrial Glands(G). These glands extend the full thickness of the Endometrium. The Endometriumchanges its structure dramatically during the menstrual cycle. The Uterus depicted here is in the Secretory Phase, in which the Uterus prepares itself for Implantation. Here, the Endometrium is very thick, and the glands are coiled into a corkscrew configuration. At this point, the Endometrium is divided into two major regions: the Functionalis (F), which constitutes about 80% of the endometrial thickness and is shed at menstruation, and the Basalis (B), which is not. During the early phase of the menstrual cycle, the Endometrium must rebuild its lost Functionalis. This phase of reconstruction is called the Proliferative Phase of the Uterus.
The inner surface of the human Uterus is shown by electron microscopy in Figure B. Here, the simple Columnar Epithelium is shown to contain secretory cells (S) and ciliated cells (C). The secretory cells elaborate and release a Glycogen-rich, mucous secretion that coats the inner uterine lining. The secretion is moved about by the beating of the motile cilia atop the ciliated cells. The epithelium rests on a highly cellular, richly vascular Lamina Propria (LP). In this micrograph, an endometrial gland (G) is caught as it opens onto the inner surface of the Uterus. This tissue sample, taken shortly before menstruation, contains many free erythrocytes (E) in the Lamina Propria. Quite a few red blood cells have, at this stage, begun to invade the epithelium itself (arrows). These changes in fine structure indicate that the Endometrium is on the verge of being sloughed.
Figure A. Light micrograph of the wall of the human Uterus in the Secretory Phase. B, Basalis; ENDO, Endometrium; EP, epithelium; F, Functionalis; G, endometrial gland; L, lumen of Uterus; MYO, Myometrium. 95 X
Figure B. Electron micrograph of the wall of a premenstrual human Uterus. C, ciliated cell; E, extravascular Erythrocyte in lamina propria; G, endometrial gland; LP, Lamina Propria; S, secretory cell; arrow, Erythrocyte free in epithelium. 600 X