Impaired developmental competence of oocytes in adult prenatally androgenized female rhesus monkeys undergoing gonadotropin stimulation for in vitro fertilization.
To determine whether prenatal T propionate exposure beginning gestational d 40-44 (early-treated) or 100-115 (late-treated) affects oocyte competence, five early-treated and five late-treated prenatally androgenized and five normal monkeys underwent recombinant human FSH injections with oocyte-retrieval after hCG administration. Serum FSH, LH, estradiol (E(2)), progesterone (P(4)), androstenedione (A(4)), T, and dihydrotestosterone were measured basally, during gonadotropin stimulation and at oocyte-retrieval; fasting serum glucose and insulin also were determined basally and at oocyte-retrieval. Follicle fluid sex steroids were analyzed. Oocyte number, nuclear maturity, and fertilization were comparable among female groups, but the percentage of zygotes developing into blastocysts was reduced in early-treated prenatally androgenized females. The intrafollicular P(4)/E(2) ratio was significantly elevated in early-treated prenatally androgenized females, whereas intrafollicular P(4)/A(4) and T/A(4) ratios were significantly increased in all prenatally androgenized females. Early-treated prenatally androgenized females demonstrated persistent LH hypersecretion. They also were unable to suppress circulating insulin levels during gonadotropin stimulation. Circulating sex steroid levels and serum P(4)/E(2), P(4)/A(4), and E(2)/androgen ratios were similar in all females. Early prenatal androgenization in monkeys receiving gonadotropins impairs oocyte developmental competence and seems to induce premature follicle differentiation in the presence of LH hypersecretion and relative insulin excess.
Dumesic
Daniel A
DA
Wisconsin Regional Primate Research Center, Department of Obstetrics and Gynecology, University of Wisconsin, Madison, Wisconsin 53715-1299, USA. ddumesic@mayo.edu
Schramm
R Dee
RD
Peterson
Eric
E
Paprocki
Ann Marie
AM
Zhou
Rao
R
Abbott
David H
DH
D000818:Animals; D016922:Cellular Senescence / Q000502:physiology; D004622:Embryo, Mammalian / Q000502:physiology; D005314:Embryonic and Fetal Development; D005260:Female; D005306:Fertilization; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D015571:Follicular Fluid / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D006728:Hormones / Q000097:blood / Q000378:metabolism; D006801:Humans; D008253:Macaca mulatta / Q000196:embryology; D009865:Oocytes / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology*
D012739:Gonadal Steroid Hormones; D006728:Hormones; D011994:Recombinant Proteins; D013739:Testosterone; D005640:Follicle Stimulating Hormone