Developmental programming: postnatal estradiol amplifies ovarian follicular defects induced by fetal exposure to excess testosterone and dihydrotestosterone in sheep.
Excess of prenatal testosterone (T) induces reproductive defects including follicular persistence. Comparative studies with T and dihydrotestosterone (DHT) have suggested that follicular persistence is programmed via estrogenic actions of T. This study addresses the androgenic and estrogenic contributions in programming follicular persistence. Because humans are exposed to estrogenic environmental steroids from various sources throughout their life span and postnatal insults may also induce organizational and/or activational changes, we tested whether continuous postnatal exposure to estradiol (E) will amplify effects of prenatal steroids on ovarian function. Pregnant sheep were treated with T, DHT, E, or ED (E and DHT) from days 30 to 90 of gestation. Postnatally, a subset of the vehicle (C), T, and DHT females received an E implant. Transrectal ultrasonography was performed in the first breeding season during a synchronized cycle to monitor ovarian follicular dynamics. As expected, number of ≥8 mm follicles was higher in the T versus C group. Postnatal E reduced the number of 4 to 8 mm follicles in the DHT group. Percentage of females bearing luteinized follicles and the number of luteinized follicles differed among prenatal groups. Postnatal E increased the incidence of subluteal cycles in the prenatal T-treated females. Findings from this study confirm previous findings of divergences in programming effects of prenatal androgens and estrogens. They also indicate that some aspects of follicular dynamics are subject to postnatal modulation as well as support the existence of an extended organizational period or the need for a second insult to uncover the previously programmed event.
1Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
A
A
Veiga-Lopez
A K
AK
Wurst
T L
TL
Steckler
W
W
Ye
V
V
Padmanabhan
D000818:Animals; D013196:Dihydrotestosterone / Q000633:toxicity*; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage / Q000633:toxicity*; D030762:Estrous Cycle / Q000097:blood / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D034461:Luteinization / Q000187:drug effects; D006080:Ovarian Follicle / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011374:Progesterone / Q000097:blood; D012756:Sheep; D013739:Testosterone / Q000633:toxicity*; D013997:Time Factors; D014463:Ultrasonography
D004343:Drug Implants; D013196:Dihydrotestosterone; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol
follicular dynamics; infertility; polycystic ovary syndrome