Older brothers, sexual orientation, and maternal immune reactivity

我们发现有证据表明，男同性恋者比异性恋者有更多的哥哥。这种“大哥”效应已经被重复无数次了。最近，我们发现了强有力的证据，证明哥哥效应源于产前。虽然没有对确切的产前机制的直接支持，但我们认为最合理的解释是免疫起源，即母亲在怀孕期间对男性胎儿发育重要的物质产生免疫反应，并且这种免疫效应随着每次男性怀孕而变得越来越可能。据推测，这种免疫效应会导致（一些）后来出生的男性产前大脑发育的改变。免疫反应的目标可能是男性胎儿脑细胞表面的分子（例如，包括下丘脑前部）。抗体可能会与这些分子结合，从而改变它们在典型的性别分化中的作用，导致一些后来出生的男性更容易被男性而不是女性所吸引。有证据表明，生男孩的母亲确实可以对男性胎儿发育中重要的一种物质（即H-Y抗原）产生免疫反应，而且随着母亲每多生一个男孩，这种免疫效应就越来越可能出现。然而，没有证据表明母体对男性胎儿发育中重要的其他男性特异性物质（例如，男性特异性蛋白质）有免疫反应，也没有证据表明母体对男性性取向发育有免疫反应。因此，为了扩大对母亲免疫反应性的研究，我们将研究生男孩的年轻母亲是否比生女孩的年轻母亲更有可能对一些男性特异性物质（例如，男性特异性蛋白质）产生免疫反应。我们还将研究是否有证据表明男同性恋者的母亲（相对于异性恋者的母亲），特别是那些以前怀孕过男性的母亲，可能对胎儿发育中重要的男性特异性物质有免疫反应。将开发针对男性特异性物质的免疫检测方法。然后，使用从母亲身上抽取的血液，检测对这些物质的免疫反应的证据。

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.