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This version published online on June 19, 2003
Endocrinology, doi:10.1210/en.2003-0146
A more recent version of this article appeared on October 1, 2003
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Submitted on January 31, 2003
Accepted on June 10, 2003

Prepubertal administration of estradiol valerate disrupts cyclicity and leads to cystic ovarian morphology during adult life in the rat. Role of sympathetic innervation*

Alzira Rosa-e-Silva1, Marco Aurelio Guimaraes1, Vasantha Padmanabhan1, and Hernán E. Lara1*

1 Dept. Physiology. Faculty of Medicine at Riberao-Preto, Universidade de Sao Paulo, Sao Paulo, Brazil, Dept of Pediatrics and the Reproductive Sciences Program, University of Michigan, Ann Arbor, MI, USA and Dept. Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, Santiago, Chile.

* To whom correspondence should be addressed. E-mail: hlara{at}ll.ciq.uchile.cl.

Administration of estradiol valerate (EV) to adult rats leads to anovulation and cystic ovarian morphology. Sympathetic ovarian nerve denervation (SONX) overcomes this disruption. In this study, we determined if EV administration to juvenile rats prevents achievement of reproductive competence, disrupts cyclicity and if this programing is facilitated via activation of the sympathetic nerve input to the ovary. Prepubertal rats were administered 2 mg EV in corn oil or corn oil alone. One half of the animals from each group underwent SONX on day 71 of life. Rats were euthanized on day 91 for determination of serum gonadotropins, progesterone, {Delta}4 androstenedione and estradiol concentrations, ovarian norepinephrine (NE) and 3{beta}-hydroxysteroid dehydrogenase (3{beta}-HSD) activities and ovarian dynamics. Results revealed that EV administration during juvenile period advanced pubertal onset, suppressed circulating LH, FSH and {Delta}4 androstenedione, increased ovarian NE, estradiol and 3{beta}-HSD activities, disrupted ovarian dynamics evidenced as absent corpus luteum and presence of ovarian cysts and culminated in anovulation. SONX restored cyclicity in these animals, normalized LH, estradiol, ovarian 3{beta}-HSD activities, and ovarian dynamics as evidenced by the disappearance of ovarian cysts and appearance of corpus luteum and restored corpus luteum function. These findings provide evidence that EV exposure during juvenile life leads to long-lasting deleterious reproductive consequences via activation of the sympathetic ovarian nerve.


Key words: Infertility • endocrine disruptors • female reproduction • PCOS







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