Variations in male sexual orientation: The role of maternal responsivity to male-specific proteins

兄弟出生顺序（FBO）的影响，平均而言，男同性恋者比异性恋者有更多的哥哥，这是男性性取向的可靠相关性。这种影响可能在出生前出现，最合理的解释是，在怀孕期间，母亲对男性胎儿发育中重要的物质产生免疫反应，这种影响在每次男性妊娠中变得更有可能，并被认为会导致一些后来出生的男性大脑发育的改变。这种反应的目标可能是胎儿脑细胞表面的蛋白质分子，因此与它们结合的母体抗体改变了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被男性而不是女性所吸引。* 我们最近通过检查同性恋男性的母亲，特别是那些以前有儿子的母亲，是否对Y染色体编码的两种蛋白质有免疫反应（相对于异性恋儿子的母亲）来验证这一假设，这两种蛋白质在男性大脑发育中起着重要作用。我们开发了针对这些蛋白质的免疫测定法，并检查了来自大约130名儿子的母亲的一部分血液样本，其中大约一半有一个同性恋儿子，沿着额外的对照样本（例如，没有男性子女的女性）。结果表明，同性恋儿子的母亲，特别是那些以前（异性恋）儿子的母亲，比异性恋儿子的母亲更有可能对这些蛋白质中的一种产生免疫反应。在下一个资助期内，我将对参与者尚未测试的部分血液（记忆B细胞）进行第二次检测。这些细胞，就像抗体本身一样，是免疫系统的一部分，在体液中工作，而不是在细胞内。我预计这项工作将验证我们先前的发现。我还计划研究来自性取向有其他变化的男孩的母亲的样本，例如，性别焦虑的男孩，尽管他们在童年时对自己的生物性别不满，但长大后可能会成为同性恋，但成年后不会表现出明显的变性。我也将在无性恋男性的母亲身上检验这些影响，这些人对其他人没有吸引力。无性恋男性也有FBO效应，这增加了一种可能性，即对他人的基本性吸引机制受到Y-连接蛋白的影响，母体对这些蛋白的免疫反应可以改变它们在胎儿大脑中的功能。如果我们的发现被证明是可靠的，那么它们可以说是过去20年来关于男性性取向的最重要的生物学发现。它们不仅解释了最可靠的相关因素之一（FBO），而且还提供了性取向背后的特定生物学机制的直接证据：母体对Y连锁蛋白的免疫反应在男性胎儿大脑发育中很重要。

The fraternal birth order (FBO) effectthat, on average, gay men have a higher number of older brothers than heterosexual menis a reliable correlate of men's sexual orientation. This effect is likely to arise before birth, with the most plausible explanation being that during pregnancy a mother develops an immune response to a substance important in male fetal development, an effect that becomes more likely with each male gestation and is thought to cause an alteration in the brain development of some later born males. The target of the response may be protein molecules on the surface of fetal brain cells so that maternal antibodies binding to them alter their role in typical sexual differentiation, leading some later born males to be attracted to men not women. ****We recently tested this hypothesis by examining whether mothers of gay men, particularly those with previous sons, have an immune reaction (relative to mothers of a heterosexual son) to two proteins, encoded by the Y chromosome, that play a significant role male brain development. We developed immune assays to target these proteins and examined a portion of the blood samples from approximately 130 mothers of sons, about half of whom had a gay son, along with additional control samples (e.g., women without male children). Results showed that mothers of gay sons, particularly those with previous (heterosexual) sons, were significantly more likely to be immune reactive to one of these proteins than mothers of heterosexual sons.****Over the next funding period, I will complete a second assay on a part of participants' blood (Memory B cells) not yet tested. These cells, like antibodies themselves, are a part of the immune system that works in bodily fluids, not within cells. I anticipate that this work will validate our earlier findings. I also plan to examine samples from mothers of boys with other variations in sexual orientation, for example, gender dysphoric boys who, despite being discontent with their biological sex in childhood, will likely grow up gay but not show significant transgenderism as adults. I will also examine these effects in mothers of asexual men, those who do not exhibit attraction to others. That asexual men also have an FBO effect raises the possibility that mechanisms for basic sexual attraction to others are affected by Y-linked proteins and that maternal immunological reactions against the proteins can alter their function in the fetal brain.****If our findings prove reliable, they are arguably the most important biological findings in men's sexual orientation in the last 20 years. They not only explain one of the most reliable correlates (FBO) but also provide direct evidence of a specific biological mechanism underlying sexual orientation: a maternal immune response to a Y-linked protein important in male fetal brain development.***