PARENT SESSION
OVARIAN GERM CELLS AND FERTILITY
Laurel
7:30 AM-10:00 AM

(267) FETAL PROGRAMMING: PRENATAL ANDROGEN EXPOSURE OF SHEEP DURING 60-90 DAYS OF GESTATION DOES NOT ALTER OVARIAN FOLLICULAR DISTRIBUTION.

Padmanabhan, Vasantha¹, Sharma, Tejinder¹, Herkimer, Carol¹, Lee, James¹, Roy, Shyamal², ¹ Departments of Pediatrics and Reproductive Sciences Program, Ann Arbor, MI² Departments of Obstetrics and Gynecology, Physiology and Biophysics, Omaha, NE

ABSTRACT- Increasing epidemiological evidence suggests that the nutritional, metabolic and hormonal environment to which the fetus is exposed during gestation may permanently program the structure and physiology of the resultant offspring. It has been well documented that exposure to high levels of androgens in utero can lead to sterility in monkeys and sheep. We found that exposure of sheep fetuses to androgens during 30-90 days of gestation culminates in disruption of reproductive cycles, altered estradiol positive feedback, polycystic ovarian morphology and reproductive failure in adult life. The objective of this study was to assess if exposure of fetuses to androgen during later part of gestation leads to polycystic ovarian morphology and reduced ovarian follicular reserve. Ovaries were collected at 2 years of age during the late follicular phase of the cycle from control ewes (n=5) and ewes exposed from 60-90 days of pregnancy to twice weekly doses (i.m.) of 100 mg testosterone propionate (n=5). These animals were cycling at the time of collection of ovaries. Ovarian weights averaged 1.97±2.93 and 2.93±0.36 gm (p=0.07) for controls (C) and prenatally-androgenized (T) sheep, respectively. Five m sections were cut, stained with hematoxylin eosin, follicular number, morphology and distribution assessed in 12 ovarian sections taken at ~ 100 intervals from each ovary. Total follicular number averaged 585±57 and 598±70 for the C and T groups, respectively. In the controls, 19.1±6.3% of the follicles were primordial, 29.9±3.7% transitory, 38.8±5.7% primary, 3.8±1.5% small preantral, 0.8±0.2% early antral, 0.8±0.5% preovulatory, 0.2±0.1% atretic antral and 5.6±5.3% atretic preovulatory. Follicular distribution in the T group were similar to C and averaged 24.4±4.2% primordial 33.3±3.9% transitory, 32.4±4.0% primary, 3.6±0.7% small preantral, 1.7±0.9% early antral, 1.4±0.5% preovulatory, 1.1±0.4% atretic antral and 1.6±1.5% atretic preovulatory follicles. None of the ovaries showed multifollicular morphology contrary to the 30-90 day T animals reported earlier. While further analysis is required to assess the degree of apoptosis in different class follicles, these results are consistent with the retention of cyclicity in the 60-90 day androgenized animals at 2 years of age. Supported by NIH HD HD41098.

KEY WORDS: Folliculogenesis, Programming, Infertility, Reproduction