The goal of this proposal is to understand male/female differentiation and behavior, a term used to describe tile sex of an animal's preferred mate. Investigations into mechanisms controlling the expression of male/female differentiation and behavior will lead to a deeper scientific understanding of sexual differentiation and psychosexual development, a need that is underscored by the current debate regarding appropriate sex assignments for children born with ambiguous genitalia. In animals, the largest body of evidence suggests that differentiation of the male-typical profile of behaviors depends on exposure to testosterone and subsequent aromatization to estradiol in the brain during a critical developmental period. Studies suggest that the medial preoptic area (MPOA), in particular, the sexually dimorphic nucleus (SDN), is involved in the expression of sex differentiation and is sexually differentiated early in development. However, it is not known whether hormone actions during development are responsible for naturally occurring variations in male/female differentiation and behavior in higher mammals. To address this question, the investigators are developing a new and unique animal model based on the spontaneous behavior of domestic rams, which display variations in sexual attraction ranging from being exclusively female oriented (FORs) to being exclusively male oriented (MORs). Experimental comparisons between MORs, FORs, and ewes under controlled conditions allow them to construct basic associations and test hypotheses that relate central nervous system structure, chemistry, and gene expression to behavior. In addition to male/female differentiation and behavior, MORs exhibit female-like levels of aromatase and estrogen receptors in the brain. During the last granting period, the investigators demonstrated for the first time the presence of an ovine analogue of the SDN (oSDN) in the sheep MPOA and found that it is larger in FORs than in MORs and ewes. The experiments in the current proposal test the general hypothesis that insufficient prenatal exposure to testosterone during the sensitive window in development leads to incomplete masculine brain differentiation engendered in the MOR phenotype. In order to test this hypothesis, the investigators will: 1) Establish whether MORs exhibit other sexually differentiated female-like traits, such as the potential to display receptive behavior, leutinizing hormone (LH) surge responses to estrogen, and neuronal Fos responses to rams; 2) Determine the effect of depriving male lamb fetuses of exposure to androgens on adult sexual activity, partner preference, neuronal Fos responses and oSDN volume; 3) Determine whether the oSDN develops prior to birth and social interactions; and 4) Identify specific genes that are differentially expressed in the preoptic area of FORs and MORs that are candidates for regulating male/female differentiation and behavior. The results of this research will be incorporated into an evolving model of the brain mechanisms controlling the expression of male/female differentiation and behavior in sheep. Further development of the sheep model will provide a valuable animal system for research in the important areas of sexual behavior, reproductive neuroendocrinology, and developmental biology.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Research Project (R01)
Project #
Application #
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Watson, Harold L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Oregon Health and Science University
Schools of Medicine
United States
Zip Code
Mirto, A J; Austin, K J; Uthlaut, V A et al. (2017) Fos Expression in the Olfactory Pathway of High- and Low-Sexually Performing Rams Exposed to Urine from Estrous or Ovariectomized Ewes. Appl Anim Behav Sci 186:22-28
Reddy, R C; Estill, C T; Meaker, M et al. (2014) Sex differences in expression of oestrogen receptor ? but not androgen receptor mRNAs in the foetal lamb brain. J Neuroendocrinol 26:321-8
Roselli, C E; Stormshak, F (2012) Ontogeny of cytochrome p450 aromatase mRNA expression in the developing sheep brain. J Neuroendocrinol 24:443-52
Alexander, Brenda M; Skinner, Donal C; Roselli, Charles E (2011) Wired on steroids: sexual differentiation of the brain and its role in the expression of sexual partner preferences. Front Endocrinol (Lausanne) 2:42
Roselli, Charles E; Reddy, Radhika C; Kaufman, Katherine R (2011) The development of male-oriented behavior in rams. Front Neuroendocrinol 32:164-9
Roselli, Charles E; Estill, Charles T; Stadelman, Henry L et al. (2011) Separate critical periods exist for testosterone-induced differentiation of the brain and genitals in sheep. Endocrinology 152:2409-15
Roselli, C E; Stormshak, F (2010) The ovine sexually dimorphic nucleus, aromatase, and sexual partner preferences in sheep. J Steroid Biochem Mol Biol 118:252-6
Roselli, C E; Estill, C T; Stadelman, H L et al. (2009) The volume of the ovine sexually dimorphic nucleus of the preoptic area is independent of adult testosterone concentrations. Brain Res 1249:113-7
Roselli, C E; Stormshak, F (2009) Prenatal programming of sexual partner preference: the ram model. J Neuroendocrinol 21:359-64
Roselli, Charles E; Stormshak, Fred (2009) The neurobiology of sexual partner preferences in rams. Horm Behav 55:611-20

Showing the most recent 10 out of 20 publications