Non-Infectious Infertility in Cattle PDF

Non-infectious Infertility in Cattle Congenital & Acquired Conditions Roberto A. Palomares, DVM, MS, PhD, DACT Images courtesy of Drost-Project  Learning Objectives 1. Understand the differences between chromosomal, gonadal and...

Non-infectious Infertility in Cattle Congenital & Acquired Conditions Roberto A. Palomares, DVM, MS, PhD, DACT Images courtesy of Drost-Project  Learning Objectives 1. Understand the differences between chromosomal, gonadal and phenotypic sex. 2. Describe the main congenital reproductive defects in cattle (Freemartinism, Segmental aplasia and incomplete fusion of the Mullerian ducts, and ovarian hypoplasia) 3. Understand the neuroendocrine mechanisms of resumption of ovarian cyclicity in cows. 4. Identify the causes and pathophysiology of anestrus and ovarian cysts 5. Describe the main clinical findings of acyclicity in dairy and beef cows 6. Differentiate follicular versus luteal cysts. Describe the clinical and ultrasound findings 7. Discuss the strategies to prevent and treat anestrus and ovarian cysts in cows  Sexual Differentiation 1. Chromosomal Sex 2. Gonadal Sex 3. Phenotypic Sex  Fig. 4-6 SRY, SOX9 Wnt 4 FoxL 2 Senger, 2003 Senger, 2003 Fig. 4-5 Fig. 4-5   Freemartinism o Results from 92% of heterosexual twin births. Fusion of chorio-allantoic portions of the twin placentas (28-30 dpc). Common blood supply between twin fetuses.   Freemartinism o Exchange of humoral (AMH) and cellular elements between fetuses. o Freemartin calves are blood cell “Chimeras”. (60 Chromosomes; 58+2) Animals that contain two cell types originating from separate zygotes.   Freemartinism o Testicular development occurs before ovarian development. o Antimüllerian hormone (AMH) from testis of male fetus inhibits the development of the paramesonephric (Müllerian) ducts in the female. AMH   Freemartinism o Reduced development of Müllerian ducts. o Small genital tract, hypoplastic ovaries, short vagina & absent cervix. o Increased development of the Wolffian ducts. o Development of epididymides, vasa deferentia & vesicular glands.   Freemartinism. Diagnosis o History of heterosexual multiple birth. o Appearance of external genitalia (small vulva, enlarged clitoris, anestrus). o Palpation or ultrasound of internal reproductive tract. o Speculum reveals short vagina (1/3) and no external cervical Os. o Use a vaginal probe.(ID 80% of cases)   Freemartinism Increased ano-genital area & enlarged clitoris. Prominent tuft of hair at the vulva o PCR: Sex chromosome XY and XX in the same animal. Detect 1 in 10,000 blood cells containing Y chromosome ($40). o Karyotyping: Blood lymphocytes cultured. Metaphase chromosome spreads examined for XY cells (laborious work and expensive)  Segmental Aplasia of the Müllerian Ducts o Autosomal recessive genes. Culling!!! o Lack of development of a portion of the Müllerian ducts (aplasia). o It involves vagina, cervix, uterus and oviducts. Hydrosalpinx. “White Heifers Disease”. High prevalence in white shorthorn females  Segmental Aplasia of the Müllerian Ducts Hydrometra o From imperforate hymen to absence of part of repro tract. Hydrometra o Absence of one horn (uterus unicornis). o Most commonly affects caudal portion of one horn. o Accumulation of endometrial secretions (hydrometra, cranial horn).  Segmental Aplasia of the Müllerian Ducts. Diagnosis o Can be misDx as pregnancy, pyometra, mucometra or ovarian cysts. o Palpation or USG & inability to pass a pipette into both uterine horns.  Incomplete Fusion of the Müllerian Ducts “Uterus Didelphys” o Autosomal Dominant gene. o Failure of complete fusion of mullerian ducts o Mostly affecting the cervix. o Double external cervical os. o Both external openings may joint into a normal internal cervical os. o One side may end in a blind diverticulum.  Incomplete Fusion of the Müllerian Ducts o May cause difficulty in passing an AI pipette o Dystocia if fetal parts pass both external cervical canals. o Fertility is affected (AI in the cervical os contralateral to ovulating ovary)  Ovarian hypoplasia o Congenital defect characterized by deficient morphologic and functional development of one or both ovaries o Ovaries small, hard consistency without palpable structures. o Inherited condition. Ovarian hypoplasia o Uni o bilateral o Unilateral: Reproductive tract can be normal. o Bilateral: Undeveloped repro tract. Steer appearance, small pelvis. o Differential Dx: Atrophy by nutritional deficiency.  Take-home message 1. Congenital defects cause of acyclicity or subfertility in heifers. 2. FM the most common congenital defect of the bovine repro system. 3. Recognition of inherited defects (e.g. SAMD). 4. Prompt identification of the defect to avoid unnecessary expenses.       Non-infectious Infertility. Acquired conditions. Roberto Palomares DVM, MS, PhD, Dip ACT Anestrus o Absence of estrus, ovulation & CL. o Inhibition of GnRH & LH secretion. X Suppressing glucose, insulin, IGF-I.  Postpartum period. Neuroendocrine Aspect FSH increases (2 to 3 d duration) resulting in emergence of the first postpartum follicular wave within 10 to 14 dpp. Follicular diameter (mm) FSH LH Days  FSH secretion is normal during the postpartum period  Lack of LH surge = No ovulation= Acyclicity  (Nett et al., 1988).  Causes of Anestrus 1. High Milk Yield o High-yielding dairy herds show increased incidence of anestrus. o Directing energy to milk production result in delayed cyclicity. >70 Lbs/day  Causes of Anestrus 2. Under-nutrition. o Limited energy intake. o Lower body reserves (BCS) Energy, protein, Minerals and vitamins 3. Negative Energy Balance 4. Metabolic diseases Energy deficit decreases release of GnRH & frequency of LH pulses. 5. Dystocia, RFM, Puerperal Metritis, pyometra.  LH Surge Elevated SCC 6. Mastitis Cortisol, endotoxins, Cytokines and Prostaglandins Negative Effects on LH. 7. Presence of the calf o Inhibits the secretion of GnRH and LH (Williams, 1990) o Hypothalamic opioid peptide B-endorphin o Serotonin, Dopamine  8. Heat stress High cortisol levels reduce GnRH & LH Prevention & Control of Postpartum Anestrus Nutritional plan according to the milk yield. Optimal nutrition during the “transition period” Minimize stress.  Bull Effect t io a ul tim i os B n o Use of temporary calf removal (48, 72 or 96h) o Appropriate Herd Health Program (Biosecurity, Vx and Dx) Lamb y col., 1999  Progestagens CIDR: Controlled Internal Drug Release  Post-partum cows (~60 dpp): CIDR + GnRH +PGF2α  Low BCS: Waste of time and money CIDR in CIDR out In conjunction with correction of management problems. Cystic Ovarian Follicles o Anovulatory follicular structures that persist for long period of time. o Higher size than a follicle. Persistent follicles behave similarly? o > 2.0 cm diameter ? that persist in the absence of a functional CL? o Prevalence 10% of dairy cows annually. Prolonged Intercalving interval o Less frequent in beef cows.  4 potential outcomes: 1. Luteinization: almost all Follicular cysts become luteal. 2. Persistency: (70 d) remains dominant (E2 & Inhibin). 3. Regression: Replaced by another follicle that ovulates. (self correction 20% of cases). 4. Turnover: Most of the cases. The cyst decreases size & replaced by a new follicular structure that develops into a new cyst. Dynamic of cyst development  Follicular Persistency and Oocyte viability (mm) 1 oocyte reduced viability 4 1 2 8 Low P4 level environment LH pulse 6 4 Days 2 Dairy cows have fast metabolism of steroids. Association with high milk  Pathogenesis 1. LH pre-ovulatory surge is absent, insufficient, or improperly timed Dominant follicle continues to grow (large & anovulatory; high E2 & Inhibin). No reduction in GnRH content in the hypothalamus No reduction LH content in the pituitary No reduction in GnRH receptors in the pituitary. Cows respond to GnRH injection with release of LH 2. Decreased sensitivity of H-H to E2. Injection of E2 fails to cause Positive Feed Back. 3. Loss of Negative Feed Back by P4. LH is released (wasted in high pulses). This leads to absence of surge 4. Other factors: Oxidative stress, negative energy balance, reduced liver function, low circulating IGF-1, increased heat shock proteins in ovaries. Follicular Cyst o May be single or multiple structures. o Thin-walled. o Several layers of granulosa cells secrete E2(dominant) o Few granulosa cells low E2 (non dominant).  Luteal Cyst o Develops from Foll cyst. theca & granulosa cells luteinize overtime. o Thickened walls. Theca and granulosa cells are luteinized. o Secretes P4 at different levels. Like luteal phase or Sub-luteal. Different from cystic CL (Normal) Ovarian Cysts. Dx 1. Behavioral and physical characteristics o Most cows do not exhibit estrus (>80%). o Nymphomania (frequent and prolonged estrus). Ovarian Cysts. Dx 2. Trans rectal examination o Structure > 2.0cm o No functional CL ? o Difficult to differentiate follicular from luteal 10% of cows misdiagnosed as having cysts had a large CL (Farin et al., 1990) Ovarian Cysts. Dx 3. Ultrasound o Follicular vs Luteal (wall thickness; 90 % accurate) > 3mm thickness  Ovarian Cysts. Tx o Objective of TX: o Increased secretion of P4 after treatment (endogenous or exogenous). o Decreased pulsatility of endogenous LH. o Sensitize Hypothalamus to E2 Use of GnRH and PGF (7 days apart)  GnRH or hCG causes luteinization of Dom cyst. ND cysts don’t respond  Ovulation of Dominant Follicle present in the ovary (estrus in 20 d)  P4 produced by the cyst reduces LH pulsatility.  Induce atresia of cysts and development of an ovulatory follicle.  P4 produced by the cyst sensitizes the H-H and uterus for PGF2a  H-H responds to high E2 & release a preovulatory surge of LH. PGF after GnRH shortens the cycle PGF alone for luteal cysts 90% effective (Dx!!!) Use of Progesterone 1. Decreases the pulsatile secretion of LH. 2. Induces atresia of cysts and development of an ovulatory follicle. 3. H-H axis primed by P4, responds to E2 produced by DF 4. Releasing a pre-ovulatory surge of LH. OVSYNCH Pregnancy 17- 25% CIDR in CIDR out 37.5% Calder, et al. J Anim Sci 1999; 77:3037-3042 Questions…