Ovary

Neonatal Exposure to Estradiol Valerate Programs Ovarian Sympathetic Innervation and Follicular Development in the Adult Rat

Abstract
A single injection of estradiol valerate (EV) to 14-day-old rats (when ovarian follicle population has been already established) disrupts cyclicity, increases the activity of key enzymes of androgen biosynthesis, and develops polycystic ovary by a causally related increase in ovarian noradrenaline. The current study was on an early window of ovarian development to look for a specific stage of development where estradiol can induce such changes in sympathetic activity and follicular development. A single dose of EV applied to rats before the first 12 hours of life rapidly increases (after 24 hours) the ovarian expression of nerve growth factor (Ngfb) and p75 low affinity neurotrophic receptor (Ngfr) mRNAs. When adults, rats presented early vaginal opening, disrupted cyclicity, appearance of follicular cyst, absence of corpus luteum and infertility. Total follicles decreased, mainly due to a reduced number of primordial follicles, suggesting that estradiol acts in the first stages of folliculogenesis, when primordial follicles are organizing. These changes paralleled with a 6-fold increase in noradrenaline (NA) concentration. No changes in NA content were found in the celiac ganglia, suggesting a local, non-centrally mediated effect of estradiol. Surgical section of the superior ovarian nerve (the main source of sympathetic nerves to the ovary), to rats neonatally treated with EV decreased the intraovarian noradrenaline, delayed vaginal opening, blocked the development of follicular cyst and that of preovulatory follicles. Therefore we can conclude that early exposure to estradiol permanently modify ovarian sympathetic activity and cause profound changes in follicular development leading to the polycystic ovary condition.

Key words: Early development • Estradiol • Neurotransmitters • Ovulation • sympathetic nerves