Bovine corpus luteum and follicles

Keywords: bovine, follicle, ovary, physiology, cycle, ovulation, corpus luteum.

This image provides a partial understanding of anatomy and physiology of ovaries during the estrous cycle. It works together with several other entries in LORI, especially, The estrous cycle, Two and three wave estrous cycles and A follicle and a corpus luteum; ultrasound.

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In the upper half of the image, note the size of the ovary compared to the author's fingers. It is fairly large; typical for a cycling cow because much of the volume in an active ovary is due to the presence of luteal tissue; an indication of ovulation and hence, cyclicity. In a non-cycling cow or a prepuberal heifer, the ovary is very small, sometimes barely the length of a finger nail.

Note the tunica albuginea around the entire ovary, thin enough in ruminants (and most other animals) to allow ovulation through the surface of the ovary.

Note:  Mares by contrast, have a thick tunica albuginea that does not allow ovulation through the surface of the ovary. For more on significance of that anatomical quirk, see this entry in LORI

The practical significance of having ovulations occur through the surface of the ovary is that part of the maturing corpus luteum (CL) comes to lie outside the tunica albuginea. The part of the CL that bulges through the tunica albuginea is called its "crown". The presence of a crown on the surface of an ovary makes it possible to know if a cow has ovulated recently. More importantly, it is possible to feel the crown of a CL during transrectal palpation.

Now consider the large follicle growing at the base of the CL in the upper image. In this case, the follicle is close to its periovulatory size; about 18 to 22 mm in diameter.

Note that the mature CL here is co-existing with a large follicle. This is often seen during transrectal ultrasonograhy as well.  Bearing in mind the fact that the CL is producing large amounts of progesterone, ask yourself if progesterone is able to suppress follicle growth. It is well known that progesterone can block the ovulation of a mature follicle, but can it suppress follicle growth? In other words, does progesterone suppress the secretion of follicle stimulating hormone (FSH)? The answer, perhaps obviously, is no; certainly not significantly.  This is why progesterone alone cannot be used to control estrous cycles with precision in any animal.   To control estrous cycles with precision, one must use progesterone (to suppress estrus and prevent ovulation) but other mechanisms must be used to control follicle growth,  To do that, one needs something to suppresses FSH, such as estrogens, androgens and if it were possible, inhibin itself (inhibin is not available for clinical use). Otherwise, follicle populations can be controlled by inducing follicles to ovulate on demand or otherwise, they can to be aspirated or physically destroyed. A new follicle wave will then grow on cue.

The image at the top of this entry could have come from a couple of places in the run of a normal estrous cycle. Using the image below, lets examine that statement. Remember that there are usually two or three waves of follicles during a bovine estrous cycle, sometimes four. This cycle has three waves. That means that two waves of follicle develop and regress during the luteal phase and it is only the follicle/s in the third wave will have the good fortune to ovulate. The other two waves will have been wasted. Why? Let me know if you ever find out.

Again, the image could only have occurred in two places: A or B. At both of those stages of the cycle, there would have been a large follicle in the presence of a mature CL. True, a large follicle could also have been present at point C, in the minutes before ovulation but a mature CL would not have been present. Instead a corpus albicans, a smaller and lighter structure, would have been seen in the image i.e. the product of destruction of a CL (luteolysis) in the absence of pregnancy.

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There is another interesting tidbit to comment on here and that is the presence of that tiny follicle in the first image. In fact, it was probably one of many in the ovary; invisible here. It is emphasized in the oval cutout. Because waves of follicle grow and regress as the estrous cycle progresses, it could belong to almost anywhere in the estrous cycle (see d, e, f &g). Most likely however it was one of those present at e, f or g, when a mature CL was present.

Ovarian activity and cervical mucus in a one month old calf

Keywords: ovary, Graafian, follicle, estrogen, spinnbarkheit

The reproductive tract of a one month old heifer. The tract appeared to be normal; the hymen already perforate.

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Although there were no macroscopically visible follicles in the ovaries, numerous small tertiary (Graafian) follicles were present (see inset).  There was also an accumulation of mucus in the cranial vagina showing spinnbarkheit similar to that seen in cows during estrus. This suggested that the follicles were steroidogenically active.

Note:
Postpartum ovarian weight in heifers increases from birth to about 4 months of age but does not increase much more than that until the onset of puberty. During this time, the rest of the reproductive tract also grows, apparently stimulated by the presence of ovarian steroids. Prepuberal (prepubertal) heifers as young as two weeks of age already show regular waves of FSH secretion preceding regular follicle waves; similar to those seen in adults. In fact, both FSH and LH reach substantial concentrations between birth and about two months of age. After that time, negative feedback from ovarian steroids appears to take effect and by three to four months of age the gonadotropins have been suppressed to baseline concentrations. The reason for this early prepuberal rise in gonadotropins is not known.

References:

N.C. Rawlings, N.C. et al. 2003 Antral follicle growth and endocrine changes in prepubertal cattle, sheep and goats. Anim. Reprod. Sci. 78:259–270

The bovine infundibulum

Keywords: anatomy, bovine, ovary, infundibulum

The complex flower-like appearance of a bovine infundibulum suspended in water. A key to this image appears below it.

The macroscopic complexity of the bovine infundibulum may exceed that the equine infundibulum. The functional significance of this is open to debate. Also remarkable is the sculpted, frilly margin of the mesopsalpinx i.e. the margin of the ovarian bursa. The bright pink appearance of the uterine tube is striking as well.  It is important to note that no color adjustments were used in the processing of this image. It was however photographed with LED lighting at 5000K, perhaps explaining why these colors are so vivid and unexpected.

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Key:

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Probable hamartoma in a Holstein neonate.

Keywords: ovary, bovine, neonate, cyst, mucus

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A female Holstein calf was submitted by RDVM having died approximately one day after it had been born. Signs of acute septicemia at post mortem examination suggested that septicemia as the cause of death. The calf weighed 46 kg

The reproductive tract was particularly interesting: The right ovary had been replaced by a large cyst weighing approximately 287g. This suggested that the cyst contained approximately 280 mL of fluid. This fluid was yellow and transparent, foaming on aspiration suggestion some content of protein. During dissection, the cyst was found to contain two smaller cysts, one of which was lined by hemorrhagic tissue approximately 1 mm thick.

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The entire ovary was retained for histological examination. Histology was examined at the sites marked Cyst 1 and Cyst 2 above. Clicking on the links Cyst 1 and Cyst 3 will open an interactive microscopy system that allows one to examine those samples. This author detected no signs of neoplasia in the wall of the cyst but occasional foci of round cell infiltrations were seen, indicating chronic inflammation due perhaps to tissue necrosis. In the opinion of Dr Donald Schlafer DVM. PhD, ACT, ABVP, this structure is probably a hamartoma, not a granulosa cell tumor. However, a definitive diagnosis was not possible without additional tissue (unavailable). A hamartoma is a focal malformation that resembles a neoplasm. It is however not a tumor, growing at the same rate as the surrounding tissue. It is essentially a disorganized mass of tissue elements normally found in that organ.

On gross examination, the left ovary appeared to be inactive. The ovary and the tip of the uterus adjacent to the ovary was retained for histology. The histology of those samples can be seen by clicking here. The ovary showed frequent nests of the stromal cells that usually surround primary and secondary follicle development. However, using the histology of ovaries of one and three month old calves as reference points, these nest appeared to be more dominant than expected and oocytes were not as frequently seen as expected. In the opinion of Dr Schlafer, this ovary appeared dysplastic, concurring with the author's opinion.

The structure of the caruncles, devoid of glandular development is easy to appreciate. In the cross section of the tip of the horn, the caruncles bulge into the lumen of the uterus. In the inter-caruncular areas, sections of rudimentary glands are visible.

The rest reproductive tract appeared to be normal other than a large accumulation of gelatinous mucus in the vagina cranial to the area of the hymen. There was no persistent hymen i.e. the vaginal lumen was continuous from the vulvar lips to the cervix, yet the mucus was thick enough to be localized to the anterior vagina.

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The caruncles appeared to be particularly well-developed, more so than normal, as did the clitoris. With an absence of follicle activity in the non-cystic ovary (an otherwise potential source of steroids) the collection of mucus in the cranial vagina and development of the caruncles and clitoris suggested that the cyst may have been endocrinologically active. Steroid assay of its fluid content is pending.
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Ovary of a three month calf

Keywords: ovary, bovine, AMH, primary, primordial, follicle, puberty

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A cross section of the ovary of a three month old heifer calf showing primary follicles (a single layer of luteal cells) and secondary follicles (multiple layers of luteal cells). Note the primordial follicles containing primary oocytes. These 2n oocytes are suspended in prophase, prior to the reduction division of meiosis. Reduction to the haploid state will only occur when a selected follicle is stimulated by LH prior to ovulation.

Primordial follicles are those that have flat epithelium surrounding the basement membrane of the oocyte. When these become more cuboidal as perhaps those are here, the follicle is termed primary instead of primordial. When the granulosa (g) cells, which are all inside the basement membrane (seen best in a high power image, where it is as labeled “bm”) multiple but have not yet formed an antrum, the follicle is termed a secondary follicle. A secondary follicle is shown below.

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Those with a well formed antrum are tertiary follicles; there are none in this image because they only form at the approach of puberty.  Outside of the basement membrane, cells from the stroma (s) accumulate and form the theca of the follicle. These follicles are too young to show the theca but it is obvious in tertiary follicles. The theca externa is fibrous in nature but the theca interna is glandular, producing androgens which are aromatized to estrogens by the granulosa cells.

The zona pellucida is already present in primary follicles but is best seen here in a secondary follicle on a high power image, where it is as labeled “zp”.

Pre antral follicles like these form anti-müllerian hormone (AMH) which prevents them from binding FSH and being recruited prematurely and en mass. AMH measurements are valuable as an indicator of the number of these pre-antral follicles and hence, the potential value of the heifer as an embryo donor.

Postpartum corpus luteum in a cow

Keywords: cow, bovine, postpartum, ovary, corpus luteum, CL

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Corpora lutea (CLs) in the ovary of a cow approximately one week after she had given birth to twins. The cow was euthanized because she had injured herself during calving. This image shows that corpora lutea are still present within the ovary for at least a week after calving; this despite the fact that they are not required for the maintenance of pregnancy for the last four months of gestation. These corpora lutea would have been producing little if any progesterone. In fact, cows can be ovariectomized after the first month of gestation and will maintain pregnancy and can calve normally. Therefore, the role of the ovaries (and corpora lutea in this case) during late gestation cattle is uncertain.

Suspect granulosa cell tumor. Beef cow

Keywords: beef, bovine, ovary, neoplasia, tumor, GCT, granulosa, polycystic

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A large, firm, polycystic structure replacing the ovary on the tract of a slaughter plant specimen from a beef cow. The bluish appearance of the cysts is probably true, judging by the correct color of the uterus. As for others in this collection, this image from 1980 was labeled as "Ovarian cyst - beef cow". Judging by the size of the tumor and the manner in which it has replaced the ovary, is far more likely that this is a polycystic form of a granulosa cell tumor. Granulosa cell tumors in cattle can be solid, may consist of a single large cyst or can be polycystic or as in this case.

Suspect granulosa cell tumor. Beef cow

Keywords: beef, bovine, ovary, neoplasia, tumor, GCT, granulosa.

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A large and almost spherical (the image was not re-touched in that regard) tumor replacing the ovary on the tract of a slaughter plant specimen from a beef cow. As for others in this collection, this image from 1980 was labeled as "Ovarian cyst - beef cow". Judging by the size of the tumor and the manner in which it has replaced the ovary, is likely that this was a cystic form of a granulosa cell tumor. Granulosa cell tumors in cattle can be solid, polycystic or as in this case, may consist of a single large cyst. This is a likely diagnosis but of course, is based only on speculation.

Luteinized follicles. COD in a cow.

Keywords: COD, cystic, ovarian, ovary, luteinization, disease, cow, production, bovine

Several follicles in one ovary show various degrees of luteinization after chronic low-grade LH stimulation. The presence of numerous follicles indicate that there was no deficiency of FSH in this cow. As is usually the case for cows with cystic ovarian disease (COD) this cow would probably not have shown estrus for a prolonged period of time.

It was once believed that these cows would not ovulate while cystic structures such as these persisted in their ovaries. However it has since been shown that estrous cycles may resume with ovulations adjacent to these cystic structures.

COD in dairy cows is usually associated with high levels of milk production; in beef cows is associated with the use of steroid containing growth promoters.

A paraovarian cyst

Keywords: paraovarian, bovine, cow, ovary, cyst, müllerian, wolffian, Kobelts

The structure shown here could either be a wolffian  (Kobelt's or mesonephric) cyst or a remnant of the müllerian system i.e. a paramesonephric cyst. Even in the human literature there is considerable confusion as to the origin of these cysts. Therefore they are often grouped loosely as "paraovarian cysts". Even the histology of the cyst may not reveal its origin, especially in veterinary medicine where these cysts had not been studied as adequately as they have in human medicine.

The cysts have virtually no practical importance because they usually do not impede normal reproductive function. They are occasionally seen on ultrasonography of the ovaries and can be palpated if they are large. 

Paraovarian cysts appear to be more common in horses than in cattle, but in theory, could exist in any species.

The incision across the ovary is incidental; made to demonstrate the presence of the corpus albicans, it's crown just visible at the site of the incision.

The corpus luteum and corpus albicans.

Keywords: CL, bovine, cow, palpation, progesterone

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The crown of a corpus luteum (CL) in an ovary of a cow.  The CL is a source of progesterone and several other hormones, including relaxin, müllerian inhibiting hormone, inhibin and even GnRH.

A CL is easily palpable per rectum in most cases and is useful for determining if the cow is having estrous cycles and in some cases, assisting one in staging the estrous cycle. The crown of a corpus luteum is seen in all species except horses where the tunica albuginea does not allow the follicle to ovulate through the surface of the ovary.

After ovulation, blood fills the antrum of the follicle, coagulating and forming a corpus hemorrhagicum. As this blood is phagocytosed, the theca granulosa of the ovarian follicle undergoes both hyperplasia and hypertrophy, folding in towards the center of the antrum.

This image shows the size of a mature CL, the author's thumb depressing the cut surface of that structure in a transected ovary.

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In the example shown below, that folding is clearly visible.

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After luteolysis, the corpus luteum undergoes regression and shrinks, forming a corpus albicans. The term "albicans" is derived from the Latin word for white but in domestic animals, this is practically a misnomer. In fact it is only in a few animals (cetaceans for example) where the corpus albicans remains as a large, substantial structure after luteolysis.  In domestic animals it only becomes a small, white body long after luteolysis is complete and in fact, is often invisible to the naked eye by that time.  Indeed, at the end of the luteal phase in domestic animals, when it is commonly referred to as a corpus alicans, the corpus "albicans" (CA) is a dark yellow-to-bright orange structure as shown here.

A CA is seen below, advanced in its luteolysis and degeneration, evidence by rays of fibrous tissue in the structure. Note that this luteal structure has a cavity in the center; a common finding in luteal tissue in cattle. It is not abnormal and is merely a function of luteinization from the theca granulosa growing but never reaching the center of what was previously a follicle. Instead of being referred to as a cystic CL/CA it is often labeled a "luteal cyst".

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A bovine granulosa cell tumor. 

Keywords: bovine, GCT, granulosa, tumor, neoplasia, cow

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A tumor in the ovary of a cull cow. This was a slaughter plant specimen with no other history. Histopathology confirmed that this was a granulosa cell tumor (GCT). That histopathology is shown in another LORI entry

Sex cord tumors of the granulosa-cell type are the most common sex cord-stromal tumors in cattle. They occur in all age groups, even in prenatal and very young calves, and in all breeds.

Steroid production has been reported but is not well characterized. Some studies show that they can produce estradiol 17 beta, progestogens and testosterone. Mammary enlargement in non-gravid affected heifers also suggest that estrogens are produced by some of these tumors.   Those findings are not surprising in terms of the de-differentiated nature of cells that normally produce steroids.

As is the case in other domestic animals  (all farm and companion animals) where granulosa cell tumors have been described, systemic metastasis is not typical but has been described in most species.

Some granulosa cell tumors in cattle can be cystic or polycystic with granulosa cells lining the cysts while others, such as this one, are solid with solid types probably in the majority. As the tumor outgrows its blood supply, areas of necrosis and hemorrhage may occur. Histologically, the neoplastic cells may be in trabecular, diffuse patterns or follicular.

Neoplastic cell types in these tumors have been described as granulosa- like or Sertoli cell- like with cells of either type predominating in separate tumors.

In this case, the tumor weighed approximately 10 kg, somewhat smaller than the largest described at 17.1 kg.

Although granulosa cell tumors such as this one may resemble Theca Cell tumors (also solid and yellow to orange in color)  Theca cell tumors consist of masses of spindle- like cells almost resembling fibromas. They are not nearly as common as granulosa cell tumors.