Female Reproductive System (longer lecture)

Resources

Ovary and Oviduct

AtlasWheater’s, Chapter 19, Female reproductive system (pgs 360-8, Ovary and Fallopian Tubes)
TextChapter 23, Female Reproductive System (pgs 773-790, Ovary and Uterine Tubes)

OBJECTIVES:

  1. Understand and identify the stages of follicular growth (primordial, primary, secondary, tertiary), as well as the changes that occur in the follicular wall during pregnancy.
  2. Identify the regional variations in the structure of the oviduct.
  3. Describe the changes that occur in the ovary and oviduct during the menstrual cycle.

The female reproductive system is composed of highly specialized organs which are in a state of constant change, from the sequential alterations characteristic of each menstrual cycle to the dramatic changes that occur during pregnancy. You will examine the ovary which contains the germ cells or oocytes, the oviduct (Fallopian tube) which receives the ovum at ovulation and conducts it to the uterus where a fertilized egg may implant. At term, the fetus passes through the uterine cervix and the vagina to the external environment.

I. OVARY

Slide 239 (ovary, monkey, H&E) WebScope ImageScope
Slide 269 (ovary, monkey, PAS) WebScope ImageScope
Slide 269-2 (ovary, monkey, PAS) WebScope ImageScope
Slide 235 (ovary, human, H&E) WebScope ImageScope
Slide 234 (ovary, human, H&E) WebScope ImageScope
Slide 234-2 (ovary, human, trichrome) WebScope ImageScope
Slide 236a (ovary, human, H&E) WebScope ImageScope

Overview: The ovaries are paired organs situated on either side of the uterus. They are attached on one edge, the hilus, to the broad ligament of the uterus by a fold of peritoneum, the mesovarium. Using slide 239, examine the overall topography of the ovary and note the numerous vessels which enter it via the broad ligament. The inner medulla (present in most slides) is highly vascular and composed of a loose connective tissue core. Examine the outer cortex of the ovary which is composed of stroma and numerous follicles in various stages of development. In slide 239, note the layer of collagenous connective tissue, the tunica albuginea [example] just below the surface epithelium (mesothelium/serosa often misleadingly referred to as “germinal epithelium”) that covers the ovary.

Examine the stroma of the cortex in slide 239 and note the whorls of closely-packed, spindle-shaped fibroblasts. The cortex also contains many oocytes (300,000- 400,000 at birth) embedded in this cortical stroma. Because of the variation in sectioning, age and stage of the cycle, you will have to study several slides in order to study all aspects of follicular development, atresia and corpus luteum formation (see W page 364, 19.7).

Primordial & Primary Follicles: Examine several primordial follicles [example] using slide 239 or 269 and note that they consist of a large oocyte surrounded by a layer of flattened follicular cells. Next examine the appearance of primary follicles [example] in which the large oocyte is surrounded by a layer of cuboidal follicular cells (also good in slide 238). These follicular cells proliferate to form a loose multi-layer, the granulosa cell layer. A rim of neutral glycoprotein, the zona pellucida (clear zone), surrounds the oocyte separating it from the surrounding granulosa cells. Slide 269 has been stained with PAS, so that carbohydrates and connective tissue are highlighted. Using this slide, examine the zona pellucida [example] of several smaller follicles. Stromal cells form a dense sheath (theca) around the follicle.

Secondary Follicles: Examine the structure of several secondary follicles [example] and observe that between the stratified granulosa cells there are large lacunae that coalesce to form the follicular antrum. The stromal cells surrounding the follicle have differentiated to form an inner layer (theca interna) of plump cells that secrete steroid precursors and an outer layer (theca externa) composed of concentrically arranged stromal cells that provide support for the developing follicle (W pg 363, 19.5). Slide 235 also has good theca layers (see below).

Mature/Graafian Follicle: With continued development, the follicle becomes a Graafian or ovulatory follicle [example] (This follicle is actually rather small to be a real Graafian follicle). The granulosa zone now consists of many layers of cuboidal follicular epithelial cells located at the periphery of the large, well-formed follicular antrum. The oocyte has attained its full size, is located eccentrically within the follicle in a small hillock, the cumulus oophorus which protrudes into the antrum. The zona pellucida is surrounded by a continuous layer of follicular cells, the corona radiata. Because of its size, the oocyte will not be present in every section of the follicle, but examine the other components of a tertiary follicle. The theca interna is separated from the granulosa cells by a distinct basement membrane. Theca externa cells are densely packed, spindle-shaped cells which blend with the theca interna cells and with the surrounding stroma. Note that the theca interna has a rich capillary vascular supply, particularly well demonstrated in slide 235 [example] (W pg 363, 19.6, see also the diagram in R pg 779, 23.7a).

Atretic Follicles: Because the contents of only one follicle are usually ovulated at a time in humans, other follicles which have been stimulated to develop must degenerate, or undergo atresia [example] (W pg 366, 19.10). Atresia is not limited to mature follicles, but may begin at any stage in follicular development. Early atretic alterations include: clumping of the nuclear chromatin (pyknosis) and shrinkage and lysis of the cytoplasm of the oocyte, granulosa or follicular cells. Examine the pyknotic granulosa cells [example], which are sloughed into the follicular antrum. The basement membrane that separates the granulosa cells from the theca interna may also thicken considerably to form a so-called “glassy membrane.” These changes are especially well illustrated in H&E slide 234 [example] and trichrome-stained slide #234-2 [example]. Make sure you are able to differentiate atretic changes from artifacts related to shrinkage due to fixation. Macrophages may eventually invade the center of the larger atretic follicles that are finally replaced by loose connective tissue.

Corpus Luteum: After ovulation, the follicle which housed the ovum collapses and becomes highly infolded and invaded by vessels, forming the corpus luteum [example] (yellow body). Examine slide 236a and observe that the corpus luteum appears pale and very folded. If the egg is fertilized and implants, the corpus luteum enlarges to become the corpus luteum of pregnancy. Examine the inner granulosa lutein cells [example] (formed from the remaining granulosa cells) and the outer theca lutein cells [example] which come from the remaining theca interna cells. Both cell types are polyhedral and filled with lipid droplets and have centrally located nuclei. The theca lutein cells are, however, considerably smaller, more darkly staining and have fewer lipid filled vacuoles than the granulosa lutein cells. They are found most prominently in the infoldings right up against the granulosa lutein layer. Granulosa lutein cells contain a pigment, lipochrome, which produces the yellowish color of the corpus luteum in an unfixed ovary. A central blood clot may be present in recently ovulated follicles.

Corpus Albicans: If the egg is not fertilized, the corpus luteum degenerates, and is gradually infiltrated with collagen and a few (if any) fibroblasts, forming the corpus albicans (white body) (W pg 360, 19.3; W pg 367, 19.11; R pg 784, 23.13) particularly evident in slide 234 stained with H&E [example] and trichrome [example]. The corpus albicans is also formed during the later half of pregnancy when the placenta takes over steroid secretion from the corpus luteum. Excellent examples of corpus albicans can be best observed in slides 234 or 236

II. OVIDUCTS (FALLOPIAN or UTERINE TUBES)

Slide 240-1 (oviduct, infundibulum, H&E) WebScope ImageScope
Slide 240-2 (oviduct, ampulla, H&E) WebScope ImageScope
Slide 241even (oviduct, isthmus, H&E) WebScope ImageScope
Slide 241odd (oviduct, uterine segment, H&E) WebScope ImageScope

The oviduct conducts the ovulated egg from the peritoneal cavity to the uterus over a period of approximately three days, during which fertilization and segmentation of the zygote occurs. There are striking regional variations in the oviducts that reflect:

1) the trapping of the egg, 2) a region where fertilization takes place, and 3) a region simply for transport to the uterus.

Examine its open end near the ovary, the infundibulum [example], in slide 240-1 and note the funnel shape and ridges of mucosa that extend as a fringe of finger-like projections known as fimbriae. Note the ciliated cells that cover the fimbria that help sweep the egg into the oviduct. Move on to slide 240-2 to trace the passage of the egg from the infundibulum through the numerous longitudinal folds of the ampulla [example] recalling that this is where fertilization usually occurs. Next is the isthmus region in slide 241even [example] that is characterized by tall branching ridges of mucosa which project into and partially fill the lumen of the oviduct. Note the numerous non-ciliated secretory (peg) cells and the ciliated cells that line the lumen. The isthmus contains tall folds and few ciliated cells, while the interstitial (or intramural because it’s within the uterine wall) segment, shown in slide 241odd, [example] has low ridges and a preponderance of secretory cells. Observe that as you progress from the infundibulum where there is a large lumen filled with many mucosal folds toward the uterus, the overall luminal diameter decreases, as does the number of ciliated cells, while the proportion of smooth muscle in the muscular layer gradually increases.

Examine the loose connective tissue of the lamina propria using slide 241even. Next, study the muscularis organized roughly into circular, oblique, and sparse longitudinal layers of smooth muscle. It has been suggested that this muscle may play a two-fold role; first, in distending the oviduct toward the ovary to aid in “capturing” the ovum; and second, in producing peristaltic waves which help propel the ovum toward the uterus. The outermost layer of the oviduct, the serosa, is highly vascular and is composed of mesothelium and thin underlying connective tissue that is continuous with the broad ligament.

 

Electron Micrographs

Uterus, Uterine Cervix, And Vagina

AtlasWheater’s, Chapter 19, Female reproductive system Ovary and Fallopian Tubes)
TextRoss and Pawlina, Chapter 23, Female Reproductive System Ovary and Uterine Tubes)

OBJECTIVES:

  1. Distinguish the cyclical alterations in the uterine endometrium and understand their hormonal bases.
  2. Describe the alterations and functional changes in the cytology of the cervix and vagina during the menstrual cycle, and during pregnancy.

I. UTERUS

Slide 244 (uterus, proliferative phase, H&E) WebScope ImageScope
Slide 243 (uterus, early secretory phase, H&E) WebScope ImageScope
Slide 245-1 (uterus, secretory phase, H&E) WebScope ImageScope
Slide 245-2 (uterus, menstrual phase, H&E) WebScope ImageScope

The uterus is a pear-shaped, hollow organ partially covered by peritoneum. Examine the overall topographical organization of the uterus from its outer serosal or adventitial covering, through the thick muscular layer (myometrium) to the mucosa (endometrium) in slide 243 (this slide is actually at a stage between proliferative and secretory).

The myometrium [example] of the uterus is composed of interwoven bundles of smooth muscle supported by dense connective tissue. Examine their arrangement into indistinct bundles, with several bundles running roughly parallel to the long axis of the body of the uterus. During pregnancy, the muscle fibers elongate, proliferate and produce collagen in response to hormonal stimulation.

The endometrium [example] is divided into two layers or strata and consists of a simple columnar epithelium and an underlying stroma that contains tubular glands that may branch near the myometrium. The stratum functionale or functional layer is the thicker, outer layer that is sloughed off with menstruation. The underlying stratum basale or basal layer is retained throughout the menstrual cycle and serves as the regenerative source of the stratum functionale. The endometrium undergoes striking cyclical modifications that depend on sequential hormonal alterations. Compare specimens from proliferative and secretory phases with the menstrual phase.

  1. Proliferative Phase (days 5-14; W pg 370, 19.15; pg 372, 19.18) In slide 244 WebScope ImageScope, the proliferative phase is underway and glands have proliferated and cover the surface. Although difficult to see in these sections, spiral arteries [example] are elongated and convoluted, and extend from the basal layer into the functional layer.
  2. Secretory Phase (days 15-28; W pg 373, 19.19) In slide 245-1 WebScope ImageScope, observe that the glands of the secretory phase endometrium appear convoluted. Toward the end of this phase, apical tissues become ischemic and glands take on a characteristic “saw tooth” appearance [example]. The endometrium reaches its maximal thickness during this period, and spiral arteries continue to grow and extend into the superficial regions of the functional layer. There is also considerable leukocyte infiltration in the stroma.
  3. Menstrual Phase (days 1-4; W pg 371, 19.16) In slide 244-2 WebScope ImageScope, much of the stratum functionalis has sloughed away, and amongst the debris are numerous blood cells (RBCs and leukocytes). Notice that the stratum basalis remains intact.

II. UTERINE CERVIX

Slide 249 (cervix, H&E) WebScope ImageScope
UCSF slide 405 (cervix, trichrome) WebScope ImageScope  (virtual slide courtesy of the University of California, San Francisco)

The uterine cervix shown in slide 249 is continuous with both the body of the uterus and the upper portion of the vagina. Note that the wall has considerable smooth muscle and much dense connective tissue. Note also the number of collagen fibers in the stroma.

The mucosa is lined by a tall columnar mucus-secreting epithelium in its uterine portion, but note the abrupt change to stratified squamous epithelium at its vaginal face. This stratocolumnar junction which should be readily identifiable in both slide 249 [example] and UCSF slide 405 [example] is frequently the site of pre-neoplastic and neoplastic (cervical cancer) changes. The mucosa is thrown into deep irregular folds known as plicae palmitae (palmate folds). During the majority of the uterine cycle these glands secrete a highly viscous mucus forming a barrier to microorganisms, while at mid-cycle (ovulation) the mucus becomes more hydrated, which facilitates sperm entry. Blockage of the openings of the cervical mucosal glands frequently results in the accumulation of secretory products within the glands, leading to the formation of dilated Nabothian cysts which may be seen in USCF slide 304 [example]. These cysts are generally benign; however, they can become clinically relevant should they become enlarged enough to cause obstruction of the cervical canal.

III. VAGINA

Slide 250-1 (vagina, H&E) WebScope ImageScope
Slide 250-2 (vagina, trichrome) WebScope ImageScope

The vagina connects the female reproductive system to the exterior of the body. At low magnification, note its three-layered structure: the mucosal lining, smooth muscle layer, and outer adventitial layer. The epithelium that lines the vagina is stratified squamous, which appears slightly vacuolated due to the presence of glycogen in these cells, which is removed during fixation.

The connective tissue of the thick lamina propria [example] contains many elastic and collagen fibers throughout and many small veins in the deeper region. The subjacent smooth muscle layers [example] are arranged in poorly defined inner circular and predominant outer longitudinal layers; it may be easier to discern the smooth muscle from the surrounding connective tissue in the trichrome-stained section [example]. The connective tissue (seen particularly well in sections stained with trichrome) of the outer adventitial layer also contains many elastic fibers, thus contributing to the overall distensibility of this region. Also evident in the adventitia in both H&E [example] and trichrome-stained sections [example] are parasympathetic ganglia that innervate the erectile tissue (i.e. the numerous small veins) of the lamina propria.

 

Placenta

 

AtlasWheater’s, Chapter 19, Female reproductive system (pgs 378-85, The placenta)
TextRoss and Pawlina, Chapter 23, Female Reproductive System (pgs 796-801, Placenta; pgs 804-9)

OBJECTIVES:

  1. Understand the histological basis of implantation and placentation.
  2. Identify the cells that form mature chorionic villi.
  3. Describe the immature and mature placental barriers.

I. PLACENTA

Slide 253 (early) WebScope [ImageScope]
Slide 255 (late) 20x WebScope [ImageScope]
Slide 255 (late) 40x WebScope  [ImageScope]

With the implantation of a zygote into the uterus, a number of changes take place in the endometrium. Cells from the embryonic trophoblast invade the uterine mucosa, secretions from these cells coalesce to form lacunae in the endometrium, which is now termed the decidua. These spaces also contain maternal blood. The trophoblast rapidly invades the decidua forming primary villi, that contain only trophoblast (outer syncytiotrophoblast and inner cytotrophoblast) cells. Mesenchyme and blood vessels form the core of the secondary villi. During the second half of pregnancy the cytotrophoblast cells disappear and the capillary basal lamina fuses with that of the syncytiotrophoblast to improve exchange.

Begin with slide 253 WebScope , which is early placenta. The entire field is filled with villi cut predominantly in cross section. Mesenchymal tissue and fetal blood vessels (filled with fetal RBCs which, in the early stages of fetal hematopoiesis, still have nuclei) make up the core of each villus which is covered by a trophectoderm shell WebScope of inner cytotrophoblast and outer syncytiotrophoblast cells. The syncytiotrophoblast cells are more eosinophilic and have smaller nuclei. As the name implies, these cells result from the fusion of many cells and thus have many nuclei per cell and no discernable lateral boundaries. In contrast, cytotrophoblast cells are clearly demarcated, have a single, large nucleus and basophilic cytoplasm. Notice that there is almost a complete ring of cytotrophoblast cells covering each villus in early placenta –these cells are thought to function as stem cells for the formation of the syncytiotrophoblast, which is why they may disappear later in pregnancy.

Study slide 255 WebScope [ImageScope] , which is a late placenta. Although you will be able to see an occasional cytotrophoblast cell, you will not be able to see forming villi in this late placenta. Examine the trophectoderm shell WebScope , which now consists of multinucleate syncytiotrophoblast cells located on the outer surface of the villi as well as an occasional residual underlying cytotrophoblast cell. The nuclei of the syncytiotrophoblast cells often form aggregates of so-called “syncytial knots WebScope that may look like specks of dirt when viewed at lower magnification. Syncytiotrophoblast cells that are bathed in maternal blood have apical surfaces specialized for absorption (microvilli), pinocytosis, and exocytosis and an appearance typical of secretory cells. Also examine the numerous macrophage-like (Hofbauer) cells WebScope that can be found within the connective tissue of the placental villi. These cells are characteristically large, with elliptical, eccentric nuclei and extensively vacuolated cytoplasm. (FE5)

Large quantities of an amorphous eosinophilic substance, fibrinoid WebScope , may also be deposited in the intervillus space in this older placenta. This material clings to the villus surface and may bind several villi together. The amount of fibrinoid in combination with the appearance of the connective tissue in the villi can be used to stage the placenta.

 

Electron Micrograph

Nipple, Aerola, and Mammary Gland

AtlasWheater’s, pgs. 386-390, Breasts
TextRoss and Pawlina, Chapters 23 pages 863-870
Ross and Pawlina, Plates, p.892-895

Mammary Gland

Objectives

  1. Be able to identify the histological components of the mammary gland, specifically the structures associated with the nipple and the areola, the overall organization into lobes and lobules, as well as secretory alveoli (acini), lactiferous ducts and sinuses and the intralobular and interlobular connective tissue.
  2. Identify and describe the histological differences between the mammary gland in adult females prior to pregnancy (inactive), during pregnancy and during lactation (active).
  3. Understand the multiple, cellular mechanisms involved in the formation and release of milk.

A. Nipple and Areola

Slide 265 Nipple, areola H&E Webscope Imagescope

The 16-20 lactiferous ducts 265 Nipple, areola H&E Webscope Imagescope, one from each lobe, open at the summit of the nipple.  These ducts are lined by stratified squamous epithelium near the opening and the lumens are frequently filled with desquamated cells.  Deeper in the connective tissue, the ducts acquire a stratified columnar appearance that is really a cuboidal duct cell sitting on a myoepithelial cell as in the sweat gland. 

Sebaceous glands 265  Webscope ImageScope are present to a variable extent, especially in the areola.  Note that the dense irregular connective tissue of the dermis is interrupted by numerous fascicles of smooth muscle 265  Webscope ImageScope that insert into the dermal connective tissue (much like arrector pili muscles).  These muscle bundles are responsible for erection of the nipples.  Occasional nerves are also present in the dermis.

B. Mammary Gland

Slide 259 Mammary gland inactive nulliparous H&E Webscope Imagescope
Slide 258 mammary gland active H&E pregnant Webscope Imagescope

Like the other tissues in the female reproductive system, alterations in circulating hormone levels result in histologically demonstrable changes in the mammary gland. Compare the examples of an inactive and active glands, noting the differences in the amount of glandular tissues. In slide #259 (inactive gland) note the dense irrengular interlobular connective tissue found between quiescent glandular lobules that consist of only a few clusters of small ducts surrounded by a mass of less dense intralobular connective tissue. Many ducts appear to be composed of 2 layers of cuboidal epithelium. The inner layer are the actual ductal epithelial cells whereas the outer layer of cells is, in fact, a layer of myoepithelial cells

In slide #258 (active gland), you can see that the amount of the glandular tissues has increased, while that of the connective tissue has decreased.  This increase involves the numbers of both the epithelial cells and myoepithelial cells.   The proliferation of these cells lead to the formation of secretory alveoli. Note also the increased cellularity (especially, the plasma cells) of the intralobular connective tissue. This tissue was probably taken from an individual before the last trimester. When compared with the inactive mammary gland, you can see that the intralobular ducts have proliferated to form additional secretory regions. Both the epithelial cells and myoepithelial cells increase in number. Alveoli #261 Alveoli Webscope ImageScope have formed, their epithelial cells have large, clear areas of apical cytoplasm, a region occupied by glycogen and lipid. Note the increased cellularity of the intralobular connective tissue. Note also that not all lobules within the gland have proliferated to the same degree. In many sections, portions of a large excretory, lactiferous duct #261 lactiferous duct Webscope ImageScope are present. The epithelial lining is again two layered, the bottom layer being principally myoepithelium. Compare the morphology of the inactive and active gland. Observe the intralobular connective tissue and note the abundance of plasma cells #261 intralobular connective tissue and note the abundance of plasma cells Webscope ImageScope. These plasma cells are the source of secretory IgA.

Female Reproductive System Practice Questions