Neuroendocrinology

Developmental Programming: Deficits in Reproductive Hormone Dynamics and Ovulatory Outcomes in Prenatal, Testosterone-Treated Sheep

Abstract
Prenatal testosterone (T) excess leads to neuroendocrine, ovarian, and metabolic disruptions culminating in reproductive phenotypes mimicking that of women with polycystic ovary syndrome (PCOS). The objective of this study was to determine the consequences of prenatal T-treatment on periovulatory hormonal dynamics and ovulatory outcomes. Pregnant sheep were injected i.m. (D30-90 of gestation, term = 147 days) with 100 mg of T propionate in cottonseed oil semi-weekly and female offspring from control and prenatal T-treated females studied during their first 2 breeding seasons. Sheep were given 2 injections of PGF_2alpha 11 days apart and blood samples were collected at 2-h intervals for 120 h, 10 min intervals for 8 h during the luteal phase (first breeding season only) and daily for an additional 15 days to characterize changes in reproductive hormonal dynamics. During the first breeding season, prenatal T-treated females manifested disruptions in the timing and magnitude of primary gonadotropin surges, luteal defects and reduced responsiveness to progesterone negative feedback. Disruptions in the periovulatory sequence of events during the second breeding season included: 1) delayed but increased preovulatory estradiol rise, 2) delayed and severely reduced primary gonadotropin surge in prenatal T-treated females having an LH surge, 3) tendency for an amplified secondary FSH surge and a shift in the relative balance of FSH regulatory proteins, and 4) luteal responses that ranged from normal to anovulatory. These outcomes are likely to be of relevance to developmental origin of infertility disorders and suggest that differences in fetal exposure or fetal susceptibility to T may account for the variability in reproductive phenotypes.

Key words: Ovulation • fetal programming • infertility

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