Grant: Discovery Grants Program - Group

We have found evidence that gay men have a greater number of older brothers than do heterosexual men. This ""older brother"" effect has been replicated numerous times. Recently, we have found strong evidence that the older brother effect is of prenatal origin. Although there is no direct support for the exact prenatal mechanism, we believe that the most plausible explanation is immunological in origin, i.e., a mother develops an immune reaction against a substance important in male fetal development during pregnancy, and that this immune effect becomes increasingly likely with each male gestation. This immune effect is hypothesized to cause an alteration in (some) later born males' prenatal brain development. The target of the immune response may be molecules on the surface of male fetal brain cells (e.g., including in the anterior hypothalamus). Antibodies might bind to these molecules and thus alter their role in typical sexual differentiation, leading some later born males to be attracted to men as opposed to women. There is evidence that mothers of boys can indeed develop an immune response to one substance (i.e., H-Y antigen) important in male fetal development, and that this immune effect becomes increasingly likely with each additional boy to which a mother gives birth. However, no evidence exists of a maternal immune response to other male-specific substances important in male fetal development (e.g., male-specific proteins), nor any evidence of a maternal immune response in men's sexual orientation development. Thus, to expand research on maternal immune reactivity, we will examine whether young mothers of boys are more likely to develop an immune reaction to a number of male-specific substances (e.g., male-specific proteins) than are young mothers of girls. We will also examine whether there is evidence that mothers of gay men (versus of mothers of heterosexual men), particularly those who had previous male pregnancies, may have had an immune reaction to male specific substances important in fetal development. Immune assays targeting male-specific substances will be developed. Then, using blood drawn from the mothers, the assays will test for evidence of immune reactivity to these substances.