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Chronic Intermittent Cold Stress Activates Ovarian Sympathetic Nerves and Modifies Ovarian Follicular Development in the Rat¹

Laboratory of Neurobiochemistry,³ Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, Santiago, Chile UMR 5102 of CNRS,⁴ University of Montpellier-2, 34095 Montpellier, France

We studied the effects of a chronic intermittent cold stress regime on sympathetic nerve activation and ovarian physiology. This paradigm (4°C for 3 h/day, Monday–Friday, for 3 or 4 wk) does not affect basal plasma levels of corticosterone. After 3 wk of stress, we detected a decrease in noradrenaline (NA) in the ovary, but after 4 wk, 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 nerve growth factor (NGF) (by enzyme immunoassay) and the intraovarian levels of its low affinity receptor mRNA (by reverse transcription-polymerase chain reaction). The activation of sympathetic nerves was followed by an increase in 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 wk 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 wk 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.

¹ Supported by Fondecyt 199-0771 and Cooperación Internacional 799-0012 (H.E.L.).

² Correspondence: Hernán E. Lara, Department of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, P.O. Box 233, Santiago, Chile. FAX: 562 737 8920; hlara{at}ll.ciq.uchile.cl

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