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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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Theresa M. Lee
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Submitted December 10, 2007
Returned for revision January 9, 2008
Accepted March 21, 2008

Behavior


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

Eila K. Roberts , Vasantha Padmanabhan , and Theresa M. Lee *

* To whom correspondence should be addressed. E-mail: terrilee{at}umich.edu.

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 (T) from gestational day (GD) 30-90 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 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 the sexual differentiation of the central nervous system and that of 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- or presence of male-typical mating behavior. To test this hypothesis we compared control females, females exposed to exogenous T from GD 30-90 (T60 females) that have virilized genitalia, and females exposed to T from GD 60-90 (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. T60 and T30 females exhibited more masculinized reproductive behavior than did controls, however the T30 animals also exhibited feminine behavior. Neither T-treated group were receptive or were mounted at rates comparable to controls. These data illustrate that variation in the timing or duration of exposure to prenatal T during a critical period for masculinization can have variable effects on defeminization; and T effects on genitalia are not entirely predictive of behavior.

Key words: Behavior • Early development • differentiation • organization





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