NANCY G. FORGER Contact |  Bio |  Research |  Publications |  Lab Members 

Developmental cell death and sexual differentiation in mice and rats.

A large number of sex differences have been described in the nervous systems of mammals. In most cases, sex differences in neural structure or neurochemistry can be traced to the actions of the steroid hormone, testosterone, produced by the testes of perinatal males. For example, testosterone creates sex differences in neuron number by controlling developmental cell death. Throughout the nervous system, many more neurons are born than will survive into adulthood, and “excess” neurons die during a period of naturally occurring cell death. Testosterone (or one of its hormonal metabolites) decreases neuronal cell death in some areas of the brain and spinal cord, while increasing cell death in others. We are investigating the cell and molecular mechanisms underlying these actions of testosterone. Specifically, we have been focusing on neurotrophic factors, and proteins of the Bcl-2 family as likely mediators of hormonally-controlled cell death. (For more information, see Xu et al., 2001, Forger et al., 2004 and Jacob et al., 2005.)

Sexual differentiation in naked mole-rats.

Naked mole-rats are subterranean rodents that live in colonies consisting of 60-80 individuals. Their social structure is highly unusual, and has been described as “eusocial.” Only a single female (the queen), and 1-3 males breed. All other individuals, known as subordinates, are reproductively suppressed and help in colony maintenance and rearing of the young. Subordinates exhibit no sex differences in behavior and even the external genitalia are remarkably undifferentiated. Subordinates never exhibit sexual behavior, despite life spans that can exceed 20 years, but become reproductively active if removed from their colonies and paired with an opposite sex mate. This raises the question of the degree to which sexual differentiation has occurred in subordinate naked mole-rats. In collaboration with Bruce Goldman at the University of Connecticut, we are examining the nervous systems of subordinate and breeding naked mole-rats. We find that most neural sex differences are absent in naked mole-rats. Instead, changes in brain and spinal cord morphology and neurochemistry are associated with breeding status. (For further reading, see Seney et al., 2006, Holmes et al., 2007 and Rosen et al., 2007.)

Sexual differentiation in spotted hyenas.

Spotted hyenas have fascinated biologists for centuries, primarily because of the extreme virilization of the female genitalia. There is no external vagina, and female spotted hyenas urinate, copulate, and give birth through a single urogenital canal that traverses a “phallus” closely resembling the male’s penis. In addition, a number of other physical and behavioral traits are “masculinized” in female spotted hyenas. This virilization of anatomy and behavior is thought to be due to the fact that spotted hyena fetuses of both sexes are exposed to elevated levels of testosterone, formed in the placenta from maternally derived pro-hormones. In collaboration with Steve Glickman at the University of California, we have been examining the nervous system of spotted hyenas. Specifically, we are asking whether sex differences found in other mammals are present in spotted hyenas. (For more information, see Forger et al., 1996, Fenstemaker et al., 1999, and
Rosen et al., 2006.)

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