Submitted February 25, 2008
Returned for revision April 1, 2008
Accepted May 13, 2008
Ovary
Developmental Programming: Exogenous Gonadotropin Treatment Rescues Ovulatory Function but Does Not Completely Normalize Ovarian Function in Sheep Treated Prenatally with Testosterone
Teresa L. Steckler ,
James S. Lee ,
Wen Ye ,
E. Keith Inskeep ,
and
Vasantha Padmanabhan *
* To whom correspondence should be addressed. E-mail: vasantha{at}umich.edu.
Abstract
Prenatal testosterone treatment leads to LH excess, ovarian follicular and ovulatory defects in the adult. These disruptions may stem from LH excess, abnormal FSH input, compromised ovarian sensitivity to gonadotropins, or intrinsic ovarian defects. To determine if exogenous gonadotropins rescues ovarian and ovulatory function of testosterone-treated sheep, the release of endogenous LH and biopotent FSH in control and prenatal testosterone-treated sheep were blocked with a GnRH antagonist during the first two breeding seasons and LH/FSH co-administered in a manner approximating natural follicular phase. An acidic mix of FSH was administered the first 36 h at 2-hourly intervals and a less acidic mix for the next 12 h at hourly intervals (different FSH preparations were used each year) and ovulation induced with hCG. Circulating FSH and estradiol responses to gonadotropins measured in 2-hourly samples differed between treatment groups in Year 1 but not Year 2. Ovarian follicular distribution and number of corpora lutea (in ewes that ovulated) tracked by ultrasonography and luteal progesterone responses were similar between control and prenatal testosterone-treated females, but differed between years. Further, hCG administration induced large cystic and luteinized follicles in both groups of females in Year 2, although the growth rate differed between control and prenatal testosterone-treated females. Our findings provide evidence that 1) ovulatory response in prenatal testosterone-treated females can be rescued with exogenous gonadotropins, 2) resultant follicular response is dependent on the nature of gonadotropic input and 3) abnormal follicular milieu may underlie differences in developmental trajectory of cystic follicles in prenatal testosterone-treated females.
Key words:
Ovary •
Follicle-stimulating hormone •
Follicular development •
Ovulation •
Ovulatory cycle
