title: Altered theca and cumulus oocyte complex gene expression, follicular arrest and reduced fertility in cows with dominant follicle follicular fluid androgen excess.
abstract: Aspiration of bovine follicles 12-36 hours after induced corpus luteum lysis serendipitously identified two populations of cows, one with High androstenedione (A4; >40 ng/ml; mean = 102) and another with Low A4 (<20 ng/ml; mean = 9) in follicular fluid. We hypothesized that the steroid excess in follicular fluid of dominant follicles in High A4 cows would result in reduced fertility through altered follicle development and oocyte maternal RNA abundance. To test this hypothesis, estrous cycles of cows were synchronized and ovariectomy was performed 36 hours later. HPLC MS/MS analysis of follicular fluid showed increased dehydroepiandrosterone (6-fold), A4 (158-fold) and testosterone (31-fold) in the dominant follicle of High A4 cows. However, estrone (3-fold) and estradiol (2-fold) concentrations were only slightly elevated, suggesting a possible inefficiency in androgen to estrogen conversion in High A4 cows. Theca cell mRNA expression of LHCGR, GATA6, CYP11A1, and CYP17A1 was greater in High A4 cows. Furthermore, abundance of ZAR1 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). There was a tendency for reduction in stage 4 follicles in ovarian cortex samples from High A4 cows suggesting that progression to antral stages were impaired. High A4 cows tended (P<0.07) to have a 17% reduction in calving rate compared with Low A4 cows suggesting reduced fertility in the High A4 population. These data suggest that the dominant follicle environment of High A4 cows including reduced estrogen conversion and androgen excess contributes to infertility in part through altered follicular and oocyte development.
authors.affiliation: Department of Animal Science, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: Adam F
authors.initials: AF
authors.lastname: Summers
authors.affiliation: Department of Animal Science, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: William E
authors.initials: WE
authors.lastname: Pohlmeier
authors.affiliation: Department of Animal Science, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Sargent
authors.affiliation: Department of Animal Science, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: Brizett D
authors.initials: BD
authors.lastname: Cole
authors.affiliation: Department of Animal Science, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Vinton
authors.affiliation: Department of Animal Science, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Kurz
authors.affiliation: Department of Animal Science, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: Renee M
authors.initials: RM
authors.lastname: McFee
authors.affiliation: USDA-ARS Roman L. Hruska U.S. Meat Animal Research Center, Clay Center, Nebraska, United States of America.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cushman
authors.affiliation: Department of Animal Science, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Cupp
authors.affiliation: Department of Animal Science, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Wood
mesh_terms: D000735:Androstenedione / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D054885:Cumulus Cells / Q000378:metabolism / Q000473:pathology; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005298:Fertility / Q000235:genetics*; D015571:Follicular Fluid / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D009865:Oocytes / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D006080:Ovarian Follicle / Q000378:metabolism* / Q000473:pathology; D011374:Progesterone / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D013799:Theca Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D004967:Estrogens; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone