165 Randel Lecture: Androgen Excess Domestic Livestock Models—What can they Tell us About the Mechanisms Underlying Anovulation?

Abstract Ovulatory disorders are a major factor in female infertility. Our laboratory has identified several populations of cows and population sheep that have excess androgen (High A4) dominant follicles ovarian cortex cultures the US Middle East with increased steroidogenic enzyme production somatic cells. Within our research herd, High A4 females irregular estrous cycles where behavioral estrus ovulation not coupled often anovulatory. Follicular waves growth, during cycle, disrupted development persistent follicles, an absence normal follicular-wave estrogen patterns blood plasma compared Controls. Increased fibrosis, oxidative stress markers pro- inflammatory lipids were present indicating inflammation. granulosa cells altered gene transcripts cell cycle arrest expression genes enriched other types resulting identity. Furthermore, secrete pro-inflammatory cytokines reduced follicle progression to later stages supporting follicular arrest. Treatment Vascular Endothelial Growth Factor 165 suppressed steroids, relieved Concentrations Anti-Mullerian Hormone (AMH) greater vs Controls both fluid culture media AMH could be contributing Many characteristics similar polycystic ovary syndrome (PCOS) women. Thus, cow excellent models unravel molecular mechanisms involved infertility anovulation.