Title: A bovine model for polycystic ovary syndrome Authors
Submitted to: Society for the Study of Reproduction Annual Meeting
Publication Type: Abstract Only
Publication Acceptance Date: March 28, 2013
Publication Date: July 1, 2013
Citation: Summers, A.F., Pohlmeier, W.E., Sargent, K.M., Kurz, S.G., McFee, R.M., Cushman, R.A., Wood, J.R., Cupp, A.S. 2013. A bovine model for polycystic ovary syndrome [abstract]. Biology of Reproduction Supplement (46th Annual Meeting of the Society for the Study of Reproduction). p. 53 (Abstract #67). Technical Abstract: Polycystic ovary syndrome (PCOS) results in the greatest single cause of anovulatory infertility in reproductive age women (affecting 5-10%). Previously, research groups have created animal models utilizing non-human primates and sheep to better understand the mechanisms involved in PCOS. However, current models are developed via exogenous hormone therapy and naturally occurring models of PCOS are lacking. Within the UNL physiology herd, we have identified two sub-populations of cows with extreme differences in mean androstenedione concentrations (High A4 = 113ng/mL; Low A4 = 6 ng/mL). These classifications are 86% repeatable over multiple estrous cycles/year suggesting intrinsic differences in steroidogenic capability. We hypothesized that androgen excess in the High A4 cows was a result of altered theca cell gene expression and exposure of oocytes to androgen excess altered oocyte maturation. Therefore, the objective of this study was to identify differences in mRNA abundance of theca steroidogenic enzymes and oocyte maternal effect genes in tissues collected from these two cow sub-populations. Beef cows (4.7 ± 0.3 yr) were synchronized (modified Co-Synch + CIDR protocol) and ovariectomies performed 36 h after PGF2alpha injection and CIDR removal. Follicular fluid, theca cells, and cumulus-oocyte complex (COC) from each dominant follicle were collected. Dominant follicles were confirmed based on size (i.e. largest follicle on the ovaries) and an estrogen-to-progesterone ratio greater than 1.0 in the follicular fluid. Dominant follicle diameter was similar between classification groups; however, follicular fluid volume tended (P = 0.09) to be greater in High A4 cows. Androstenedione production was 19-fold greater (P = 0.0004) for High A4 (n = 53) compared to Low A4 (n = 28) cows. High A4 cows also had a 2-fold increase (P = 0.01) in follicular fluid dehydroepiandrosterone (DHEA) concentrations. Previous studies indicate increased androgen production as a hallmark characteristic of the PCOS phenotype, thus gene expression of the theca cells of High and Low A4 cows was compared. In High A4 cows, expression of CYP11A1 was 3.3-fold greater (P = 0.02) and CYP17A1 15.5-fold greater (P = 0.03). The affect of increased intrafollicular androgen levels on cumulus-oocyte gene expression in the dominant follicle was also examined. Abundance of ZAR1 was decreased 11-fold (P = 0.05) while conversely, NLPR5 had a tendency (P = 0.12) to be increased 13.5-fold in COCs from High A4 cows. Taken together, increased androgen production in High A4 cows alters gene expression and/or mRNA stability during oocyte growth and maturation which may reduce fertility success. Furthermore, these data indicate cows classified High A4 display similar increases in androgen production and alterations in oocyte mRNA abundance consistent with findings in PCOS patients. We propose development of a naturally occurring model for PCOS, which can improve our understanding of PCOS and development of therapies that could aid in the treatment of this disorder. USDA is an equal opportunity provider and employer.