Cyclicity phenotype and ovarian cortex androgen secretion in androgen excess cows are predictive of plasma steroid and lipids, liver enzymes and follicular fluid cytokines

Authors: HART, MARIAH - University Of Nebraska; ABEDAL-MAJED, MOHAMED - University Of Nebraska; SPURI-GOMES, RENATA - University Of Nebraska; SNIDER, ALEXANDRIA - University Of Nebraska; KURZ, SCOTT - University Of Nebraska; BERGMAN, JEFF - University Of Nebraska; MCFEE, RENEE - University Of Nebraska; CASEY, CAROL - University Of Nebraska; LEMLEY, CALEB - Mississippi State University; Cushman, Robert - Bob; DAVIS, JOHN - Nebraska Medical Center; WOOD, JENNIFER - University Of Nebraska; CUPP, ANDREA - University Of Nebraska

Submitted to: Society for the Study of Reproduction Annual Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 5/1/2018
Publication Date: 7/2/2018
Citation: Hart, M.L., Abedal-Majed, M.A., Spuri-Gomes, R., Snider, A.P., Kurz, S.G., Bergman, J.W., McFee, R.M., Casey, C.A., Lemley, C.O., Cushman, R.A., Davis, J.S., Wood, J.R., Cupp, A.S. 2018. Cyclicity phenotype and ovarian cortex androgen secretion in androgen excess cows are predictive of plasma steroid and lipids, liver enzymes and follicular fluid cytokines [abstract]. Society for the Study of Reproduction Annual Meeting. Abstract Program p. 381-382. Available: https://www.ssr.org/sites/ssr.org/files/2018_annual_meeting_abstracts_updated.pdf

Interpretive Summary:

Technical Abstract: We have identified a population of cows that produce excess androstenedione (A4; High A4; >40 ng/ml A4; control <20 ng/ml A4) in follicular fluid of the dominant follicle, secrete excess A4 (43-fold higher) in ovarian cortex cultures, display irregular cyclicity, are often anovulatory, and have reduced fertility. We hypothesized that High A4 cows secreting greater A4 in ovarian cortex cultures would have altered hormone metabolism, plasma hormones, lipids, and greater pro-inflammatory cytokines in follicular fluid compared to controls. Cows (n=17) were synchronized to induce a new follicular wave. Follicle development was monitored and blood collected. Ovariectomies were performed 36-42 hours after PGF2a, and ovarian cortex cultures and liver biopsies were conducted to measure A4 concentrations in media and to determine liver enzyme activity, respectively. High A4 cows were further categorized into: High A4-Irregular, or High A4-Ovulatory based on whether they ovulated or were anovulatory/stimulated to ovulate. High A4-Ovulatory and High A4-Irregular cows produced greater amounts of A4 in the first 3 days of cortex culture when compared to controls (High A4-Ovulatory vs. Controls, P < 0.005, 72.0-fold increase; High A4-Irregular vs. Controls, P < 0.02, 53.0-fold increase). High A4-Ovulatory cows tended (P < 0.10) to have decreased circulating 17-b estradiol (E2; 2.0-fold) compared to controls. There was a tendency (P < 0.10; R = -0.67; R2 = 0.45) for decreased activity of hepatic P450 3A (RLU/min/mg protein; metabolizes E2) as cortex culture A4 increased. There was a relationship for increased activity (P < 0.05; R = 0.78; R2 = 0.60) of hepatic P450 2C (RLU/min/mg protein; metabolizes P4) as cortex culture A4 concentrations increased. Circulating triglycerides tended (TG; P < 0.06; R = -0.60; R2 = 0.36) to decrease as cortex culture A4 concentrations increased. To elucidate differences in pro-inflammatory cytokines and chemokines, we evaluated follicular fluid from cows (High A4: n = 15; Control: n = 15). CXCL9 (P < 0.05; R = 0.37; R2 = 0.14) concentrations decreased and CXCL10 concentrations tended (pg/ml; P < 0.08; R = -0.33; R2 = 0.11) to decrease as cortex culture A4 concentrations increased. CD40L (P < 0.04; R = 0.40; R2 = 0.16) and IL-17A (P < 0.04; R = 0.38; R2 = 0.15) concentrations increased as cortex culture A4 concentrations increased. These data indicate that amount of A4 secreted from the ovarian cortex can predict differences in liver steroid inactivation enzymes and circulating TGs. Whether High A4 cows are ovulatory or have irregular cyclicity may predict alterations in E2. Furthermore, correlations with chemokines and cytokines and culture A4 suggest that there are alterations in pro-inflammatory cytokines and chemokines as concentrations of A4 increase, which may affect altered cyclicity. Thus, the amount of A4 secreted into media correlates with plasma metabolites, steroid hormone concentrations, hepatic inactivation enzymes, TGs, and inflammatory markers may contribute to the ovulatory status and infertile phenotype of High A4 cows. This research was funded through USDA grant 2013-67015-20965.