Ovary

Chronic Intermittent Cold Stress Activates Ovarian Sympathetic Nerves and Modifies Ovarian Follicular Development in the Rat

Abstract

We studied the effects of a chronic intermittent cold stress regime on sympathetic nerve activation and ovarian physiology. This paradigm (4°C for 3h/day, Monday through Friday, for 3 or 4 weeks) does not affect basal plasma levels of corticosterone. After 3 weeks of stress, we detected a decrease in noradrenaline (NA) in the ovary, but after 4 weeks this ovarian neurotransmitter concentration increased over that of unstressed control rats. To analyze whether this effect on NA is preceded by an activation of the neurotrophic factor system responsible for growth and survival of sympathetic neurons, we measured both NGF (by EIA) and the intraovarian levels of its low affinity receptor mRNA (by RT-PCR). The activation of sympathetic nerves was followed by an increase in nerve growth factor (NGF) concentration, without affecting the ovarian levels of either NGF or the mRNA of its receptor. Interestingly, follicular development changed during the stress procedure; after 3 or 4 weeks of stress we found a decrease in preantral healthy follicles without a compensatory increase in atresia. Concomitantly with the increase in NA and NGF in the ovary, we observed that a new population of follicles with hypertrophied thecal cell layers appeared after 4 weeks of stress. These results suggest that chronic stress, through an intraovarian neurotrophin-mediated sympathetic activation, produces changes in follicular development that could lead to an impairment of reproductive function.