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BOR - Papers in Press, published online ahead of print May 31, 2006.
Biol Reprod 2006, 10.1095/biolreprod.106.052795
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Submitted March 28, 2006
Returned for revision April 11, 2006
Accepted May 23, 2006

Neuroendocrinology


Sex Differences and the Development of the Rabbit Brain: Effects of Vinclozolin

Erin S. Bisenius , D.N. Rao Veeramachaneni , Ginger E. Sammonds , and Stuart Tobet *

* To whom correspondence should be addressed. E-mail: stuart.tobet{at}colostate.edu.

Abstract
The preoptic/anterior hypothalamic area (POA/AH) is one of the most sexually dimorphic areas of the vertebrate brain and plays a pivotal role in regulating male sexual behavior. Vinclozolin is a fungicide thought to be an environmental anti-androgen, which disrupts masculine sexual behavior when administered to rabbits during development. In this study, we examined several characteristics of the rabbit POA/AH for sexual dimorphism and endocrine disruption by vinclozolin. Pregnant rabbits were dosed orally with vinclozolin (10 mg/kg body weight) or carrot paste vehicle once daily for 6 weeks beginning at mid-gestation and continuing through nursing until post-partum week 4. At 6 weeks, offspring were perfused with 4% paraformaldehyde and brains processed for immunocytochemical localization of tyrosine hydroxylase, calbindin, gonadotropin-releasing hormone (GnRH-1) or Nissl stain. There were significant sex differences in the distribution of calbindin in the POA/AH and the size of cells in the dorsal POA/AH (values greater in females than in males) but not in the number or distribution of tyrosine hydroxylase or GnRH neurons. In both sexes, exposure to vinclozolin significantly increased calbindin expression in the ventral POA/AH and significantly decreased number of GnRH neurons selectively in the region of the organum vasculosum of the lamina terminalis (OVLT) but not more caudally in the POA/AH. This is the first documentation of a sexually dimorphic region in the rabbit brain, and further supports the use of this species as a model for studying the influence of vinclozolin on reproductive development with potential application to human systems.

Key words: Neuroendocrinology • Early development • Gonadotropin-releasing hormone • Hypothalamus • Male sexual function


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[Abstract] [Full Text] [PDF]


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