D E S I G N E D AN D D E V E L O P E D U N D E R T H E AE G I S O F

NAHEP Component-2 Project “Investments In ICAR Leadership In Agricultural Higher Education”

Division of Computer Applications
ICAR-Indian Agricultural Statistics Research Institute
 Course Details

Course Name Female Infertility

Unit V

Lesson 6 Pathogenesis symptoms histology and steroid

level

Disclaimer : Presentations are intended for educational purposes only and do not replace independent professional
judgement. Statement of fact and opinions expressed are those of the presenter individually and are not the opinion or
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completeness of the information presented.

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 Created by

Name Role University

Orissa University of Agricultural

BASANTI JENA Content Creator
and Technology, Bhubaneswar

Sri Venkateswara Veterinary

K VEERA BRAMHAIAH Unit Reviewer
University, Tirupati

KRISHNAKUMAR Tamil Nadu Veterinary and Animal

Course Reviewer
KARUPPASAMY Sciences University, Chennai

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 PATHOGENESIS

• Ovarian dysfunctions like cysts occur most often during the early postpartum
period when there is a transition from the noncyclic condition during
pregnancy to the establishment of regular cyclicity.
• It is generally accepted that cystic follicles develop due to a dysfunction of the
hypothalamic-pituitary-ovarian axis.
 HYPOTHALAMIC-PITUITARY DYSFUNCTION

• Increased circulating estradiol concentrations have positive feedback effects

on the hypothalamus when circulating progesterone concentrations are low.
This results in the release of gonadotropin-releasing hormone (GnRH) that, in
turn, stimulates the pituitary to release the preovulatory luteinizing hormone
(LH) surge.
• Cystic ovarian disease develops as a result of the absence of a preovulatory
LH surge that is caused by a disturbance in the positive feedback effect of
estradiol on the hypothalamus
HYPOTHALAMIC-PITUITARY DYSFUNCTION

• The most common cause of COD is hypothalamic unresponsiveness to

estradiol. Cows that develop COD do not have a preovulatory LH surge
even when the dominant follicle secretes high concentrations of estradiol.
• Unresponsiveness to estradiol may be associated with decreased
hypothalamic GnRH content and may develop if an LH surge is not
followed by ovulation.
• After an LH surge, exposure to progesterone may be necessary to up-
regulate estradiol receptors in the hypothalamus and re-establish
responsiveness to estradiol.
 HYPOTHALAMIC-PITUITARY DYSFUNCTION

• The progesterone could lead to the formation of ovarian follicular cysts.

• Intermediate levels of progesterone (0.1–1.0 ng/mL) have been shown to
prevent ovulation and promote persistence of dominant follicles in normal
cycling cows.
• During the follicular phase in a normal cow,
1. The tonic center in the hypothalamus secretes GnRH at a high frequency
2. Stimulating a high frequency mode of LH secretion
3. Maturation of the dominant follicle
4. Follicle secretes increasing concentrations of estradiol
5. That ultimately reach a threshold adequate to trigger the surge center of
the hypothalamus to release GnRH
6. In quantities adequate to stimulate a preovulatory surge of LH
7. The preovulatory surge of LH will induce ovulation of the dominant follicle.
 HYPOTHALAMIC-PITUITARY DYSFUNCTION

• Thus, the preovulatory surge of LH is blocked, ovulation does not occur

and the dominant follicle persists.
• The tonic center of the hypothalamus is not affected by intermediate
progesterone, allowing the high frequency, tropic pattern of LH secretion
to be maintained. This provides the cyst the gonadotropic support it needs
to function.
HYPOTHALAMIC-PITUITARY DYSFUNCTION

• Hypothalamic pituitary function and follicular growth/development may

be affected by negative energy balance (NEB) through
metabolic/hormonal adaptations.
• In addition, in the situation of NEB, the expression of genetic hereditary
factor(s) associated with COD may be promoted or the functional
importance may increase, which in turn may affect follicle growth and
hypothalamic-pituitary function
 HYPOTHALAMIC-PITUITARY DYSFUNCTION

• Low insulin/IGF-1 concentrations insufficiently (+) stimulate follicle cell

proliferation and oestradiol-17β production.
• The reduced oestradiol-17β feedback, and low insulin/IGF-1
concentrations results in a reduced gonadotropin release.
• Dominant follicle growth is retarded and the altered follicular growth
pattern and oestradiol-17β production disrupt the hypothalamo-
pituitary- gonadal axis.
• This finally results in an aberrant LH-surge and the subsequent
development of a cystic follicle.
HYPOTHALAMIC-PITUITARY DYSFUNCTION

• Leptin is a recently “new” hormone, produced by adipocytes, and is

regarded as the ultimate factor linking metabolic status to reproduction.
• In the postpartum dairy cow, a clear relationship between leptin profiles
and first postpartum ovulation is lacking.
• Although a minimum permissive level of leptin seems required to induce
the first postpartum LH surge.
• Therefore, leptin may play a role in early post-partum cyst development.
HYPOTHALAMIC-PITUITARY DYSFUNCTION

• Another contributing factor that may play a role in the pathogenesis of

COD is delayed uterine involution and early postpartum problems such as
retained foetal membranes, milk fever and metritis.

• High producing cows under such stressors are prone to various

reproductive problems especially COD.

• Endogenous opioid peptides (produced in the hypophysis and brain) are

believed to block the oestrogen-induced LH surge and the release of
hypothalamic GnRH.
 OVARIAN/FOLLICULAR DYSFUNCTION

• A FSH surge stimulates the development of a new follicular wave, from

which a single dominant follicle is selected at the time of deviation.
• Through a positive feedback loop oestradiol stimulates GnRH and LH
pulsatility, which in turn supports growth and development of the
dominant follicle.
• Upon reaching preovulatory size, follicular steroidogenic activity reaches a
peak and produces a preovulatory oestradiol surge.
 OVARIAN/FOLLICULAR DYSFUNCTION

• A primary dysfunction at the level of the follicle may disrupt the

hypothalamic-pituitary-ovarian axis and cause the formation of COD.
• Alterations in LH receptor expression and content may cause anovulation
of the follicle.
• Follicle stimulating Hormone (FSH) and LH receptor numbers in granulosa
cells of cysts are decreased when compared to normal follicles.
 OVARIAN/FOLLICULAR DYSFUNCTION

• Oestrogen-active cysts show a higher expression of 3 – hydroxyl steroid

dehydrogenase messenger Ribonucleic Acid (mRNA), a steroidogenic
enzyme and cows developing a cyst have increased oestradiol
concentrations during the early stages of follicular dominance.
• Matrix metalloproteinase’s (MMP) could be involved in the formation of
cysts: higher proMMP-2 and -9 levels were present in the follicular fluid of
cysts than in the follicular fluid of normal dominant follicles.
 SYMPTOMS

• The symptoms are divided into two types. They are

– Nymphomaniac cows
– Anoestrus cows
• Nymphomaniac animals shows,
– Prolonged or continuous oestrus and show frequent irregular oestrus.
– Nervous, restless and seeking other animals and continuously bellow.
– Mount on other animals and will not allow other animals to mount on
it.
– Increased Homosexual behaviour
 SYMPTOMS

• These animals behave like a Bull; they are called as “BULLERS”.

• Follicular cyst and luteal cyst secretes oestrogen, results in continuous

oestrus

• Relaxation of Pelvic ligaments, especially Sacro-sciatic ligament.

• Dipping of pelvis.

• Sinking of Croup muscles.

• Elevation of base of the tail. This condition is called as “STERILITY HUMP”.

 Sacrosciatic relaxation

COD can lead to relaxation of Sacro-sciatic ligaments and the apparent elevation of
the tail head
STERILITY HUMP
 HISTOLOGY

• Histologically, the ovary will show loss of ovum and granulosa cells.

• But, scanty layer of granulosa cells may be seen in few cases.

• Theca interna becomes flocculent and oedematous.

• Fallopian tube is filled with yellow fluid.

• There is a hyperplasia of endometrial mucosa and there will be cystic

dilatation of endometrial glands.
 HISTOLOGY

• These changes are noticed commonly in Nymphomaniac and Anoestrus

cows affected with COD.
• The hyperplasia of mucosa and cystic dilatation of uterine glands
resembles Swiss cheese in appearance.
• The Endometrium affected in such a way is called as “SWISS CHEESE
ENDOMETRIUM”.
• In COD affected animals, there will be an enlargement and hypertrophy of
Pituitary and Adrenal glands.
• The affected animal will have thick neck and masculine appearance.

• It resembles a steer. This condition is called as “ADRENAL VIRILISM”

• In these animals, the 17-ketosteroids from the adrenal gland are excreted
through urine.

• The masculinity is not due to the adrenal gland, but it is due to continuous
action of steroids from cystic ovary.

• In long standing case of COD, mucometra or hydrometra may develop.

 GUESS WHAT???

• _________________ and ______________ receptor numbers in granulosa

cells of cysts are less when compared to normal follicles.

• Bacterial endotoxins released in the uterus may stimulate cortisol

secretion, which in turn suppresses pre-ovulatory surge-like release of LH
leads to COD (T/F)
• In normal cow ovulation is due to

– Hypothalamic tonic center secretes high frequency GnRH

– High frequency LH secretion from anterior pitutary leads to

maturation of the dominant follicle

– Estradiol from follicle trigger the surge center to release GnRH

– Preovulatory surge of LH
• i. a and b are correct.
• ii. a, b and c are correct.
• iii. a, b, c and d are correct.
• iv. c and d are correct.
THANK YOU