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ARS Home » Plains Area » Clay Center, Nebraska » U.S. Meat Animal Research Center » Nutrition, Growth and Physiology » Research » Publications at this Location » Publication #299993
Title: Altered theca and cumulus oocyte complex gene expression, follicular arrest and reduced fertility in cows with dominant follicle follicular fluid androgen excess

Author
item SUMMERS, ADAM - University Of Nebraska
item POHLMEIER, WILLIAM - University Of Nebraska
item SARGENT, KEVIN - University Of Nebraska
item COLE, BRIZETT - University Of Nebraska
item VINTON, REBECCA - University Of Nebraska
item KURZ, SCOTT - University Of Nebraska
item MCFEE, RENEE - University Of Nebraska
item Cushman, Robert - Bob
item CUPP, ANDREA - University Of Nebraska
item WOOD, JENNIFER - University Of Nebraska

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/21/2014
Publication Date: 10/1/2014
Publication URL: http://handle.nal.usda.gov/10113/59747
Citation: Summers, A.F., Pohlmeier, W.E., Sargent, K.M., Cole, B.D., Vinton, R.J., Kurz, S.G., McFee, R.M., Cushman, R.A., Cupp, A.S., Wood, J.R. 2014. Altered theca and cumulus oocyte complex gene expression, follicular arrest and reduced fertility in cows with dominant follicle follicular fluid androgen excess. PLoS One. 9(10):e110683.

Interpretive Summary: Ovarian steroid hormone production is an important component of fertility in mammalian females. Excess production of the steroid hormone, androgen, in female mammals is associated with decreased fertility. In the cow, androstenedione (A4) is the major androgen and in follicular fluid collected during estrus, we identified HIGH A4 and LOW A4 sub-populations of cows. HIGH A4 cows are removed from the herd at a greater rate than LOW A4 cows due to reproductive failure, suggesting reduced fertility. Based on studies of women with androgen excess, we hypothesized that androgen excess in HIGH A4 cows was due to increased expression of steroidogenic enzyme genes and that this increased androstenedione caused altered expression of genes associated with the quality of the egg. To test this hypothesis, estrous cycles of cows were synchronized and ovaries were removed during estrus. In High A4 cows, follicular fluid androstenedione concentrations were greater and expression of genes controlling steroidogenesis was greater than in LOW A4 cows. Furthermore, there were changes in the abundance of genes in the egg that are responsible for controlling early embryonic development, indicating decreased egg quality in High A4 cows. Therefore, nutritional or genetic mechanisms that lead to increased androgen production and decreased estradiol production in the bovine ovary may contribute to decreased fertility and decreased herd life.

Technical Abstract: To date, animal models with naturally occurring androgen excess have not been identified. Serendipitously, we discovered two subpopulations of cows with dramatically different follicular fluid androgen concentrations in dominant follicles within our research herd. In the cow, androstenedione is the major androgen and in bovine follicles aspirated from 6-60 hours after induced corpus luteum lysis, we identified High androstenedione (A4; > 40 ng/ml; mean = 102) and Low A4 (< 20 ng/ml; mean = 9) sub-populations. Interestingly, Low A4 cows have a 10% greater calving rate than High A4 cows, suggesting reduced fertility in the High A4 subpopulation. Based on human studies, we hypothesized that androgen excess in High A4 cows was due to increased expression of theca cell steroidogenic enzymes causing altered expression of mRNAs associated with oocyte competence. To test this hypothesis, estrous cycles of cows were synchronized and ovariectomy performed 36 hours later. In High A4 cows, follicular fluid A4 concentration was 24.5-fold greater and theca cell mRNA expression of LHCGR, GATA6, CYP11A1, and CYP17A1 was greater than Low A4 cows. Furthermore, abundance of ZAR1, a maternal effect gene, was decreased 10-fold in cumulus oocyte complexes from High A4 cows, whereas NLRP5 abundance tended to be 19.8-fold greater (P = 0.07). High A4 cow gene expression profiles and steroid concentrations are similar to women with PCOS. Thus, this cow population appears to be a promising new animal model for studying certain aspects of hyperandrogenism in women.