We propose continued studies of the life-span development of 64 male and female rhesus monkeys exposed to normal or atypical levels of prenatal androgen. Treatments were 35-40 days long and timed to the start of the second or third of gestation. Endogenous prenatal androgen effects were reduced by twice daily administration of flutamide, and androgen-receptor blocker. Weekly injections of testosterone enanthate increased androgen. Continuation of this project will allow investigation of the behavioral, neuroendocrine, and cognitive consequences of alterations in prenatal androgen exposure in socially-living rhesus monkeys during the pubertal transition and as adults. These studies provide fundamental information about the effects of prenatal androgens on development of sexual an sex-typed behavior in a primate with a complex social organization and extended sexual development. Subjects will go through puberty and enter adulthood during this funding period. We plan to explore how altered prenatal androgens affect pubertal change and adult reproductive behavior. Because none of our hormonal treatments altered the genitalia of experimental females in a manner to prevent pregnancy we can explore whether exposure to much lower levels of prenatal androgen than previously studied after female reproductive and maternal behavior. In addition to studied of reproductive behavior and neuroendocrine function we will investigate differences in vocal communication, otoacoustic emissions (OAEs), cognition, and neural sex differences. Males and females differ in vocal repertoires. We will investigate the development of these sex differences and relate them to differences in prenatal hormone exposure. Spontaneous and click-evoked OAEs offer a noninavise window into neural function and differ between male and female humans. We will investigate this sex difference in rhesus monkeys and relate it to our atypical prenatal androgen treatments. The most striking human cognitive sex differences is in spatial cognition. We will study sex differences in spatial cognition in group-living monkeys and investigate the relationship between spatial cognition and atypical prenatal androgen exposure. Exploratory studies will relate behavior differences to noninvasively imaged difference in brain structure. We are exploring the hypothesis that the timing of altered prenatal androgens differentially affects sexual behavior, anatomical, neuroendocrine function, and cognition. Particularly significant is our finding that androgen manipulations can affect behavioral and neuroendocrine development without any anatomical changes. These nonhuman primate studies are relevant to human gender development both normative individual variation and the occurrence of gender dysphoria. The range of effects we will investigate reflect the effects of altered hormonal conditions that could presumably occur in humans from maternal illness or exposure to environmental toxins. This research extends and develops the notion that alterations in the prenatal androgen that leave no external indicators may produce life-long alterations in development and adult behavior.
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