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BOR - Papers in Press, published online ahead of print April 2, 2008.
Biol Reprod 2008, 10.1095/biolreprod.107.067074
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BIOLOGY OF REPRODUCTION 79, 43–50 (2008)
DOI: 10.1095/biolreprod.107.067074
© 2008 by the Society for the Study of Reproduction, Inc.


research-article

Differential Effects of Prenatal Testosterone Timing and Duration on Phenotypic and Behavioral Masculinization and Defeminization of Female Sheep1

Eila K Roberts 3 7, Vasantha Padmanabhan 4 6, and Theresa M Lee 2 3 5 6

Departments of Psychology,3 Pediatrics,4 and Neuroscience;5 and Reproductive Sciences Programs;6 and School of Natural Resources,7 University of Michigan, Ann Arbor, Michigan 48109

ABSTRACT

The process of sexual differentiation leaves genetically female individuals at risk of being masculinized by exogenous androgens. Previous research with sheep indicates that exposure to excess testosterone from Gestational Day (GD) 30 to GD 90 of the 147-day gestation masculinizes and defeminizes behavior as well as genitalia. Lower doses and shorter durations produce animals with varying degrees of genital virilization and alterations of the hypothalamic-pituitary-gonadal axis, but to our knowledge, the effects on complex behavior and its prediction by the amount of external virilization have not been explored. Previous research in rodents has suggested that sexual differentiation of the central nervous system and the external genitalia can be dissociated. Therefore, we hypothesized that the extent of virilization of external genitalia would not be predictive of the lack of female-typical, or the presence of male-typical, mating behavior. To test this hypothesis, we compared control females, females exposed to exogenous testosterone from GD 30 to GD 90 (T60 females) that have virilized genitalia, and females exposed to testosterone from GD 60 to GD 90 (T30 females) that have female-typical genitalia. Both natural behavioral estrus in the flock and hormonally controlled behavioral tests were used to explore reproductive behavior. The T60 and T30 females exhibited more masculinized reproductive behavior than the controls; however, the T30 females also exhibited feminine behavior. Neither testosterone-treated group was receptive or was mounted at rates comparable to those of controls. These data illustrate that variation in the timing or duration of exposure to prenatal testosterone during a critical period for masculinization can have variable effects on defeminization and that the effects of testosterone on genitalia are not entirely predictive of behavior.

behavior, differentiation, early development, organization


FOOTNOTES

1Supported by U.S. Public Health Service grants R01 P01-HD44232 (to V.P. and T.M.L.) and R01 HD41098 (to V.P.).

Correspondence: 2Theresa M. Lee, Department of Psychology, University of Michigan, 530 Church St., Ann Arbor, MI 48109-1043. FAX: 734 763 7480; e-mail: terrilee{at}umich.edu







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Copyright © 2008 by the Society for the Study of Reproduction.