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

男性性取向的变化：母亲对男性特异性蛋白质的反应的作用

• 批准号: RGPIN-2016-05390
• 负责人: Bogaert, Anthony
• 金额: $ 2.26万
• 依托单位: Brock University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=645709
• 关键词: Variations; male; sexual; orientation; role

The fraternal birth order (FBO) effect—that, on average, gay men have a higher number of older brothers than heterosexual men—is 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.***

兄弟会出生顺序(FBO)效应--平均而言，同性恋男性比异性恋男性有更多的哥哥--是男性性取向的可靠关联。这种影响很可能在出生之前就出现了，最合理的解释是，在怀孕期间，母亲对一种对男性胎儿发育至关重要的物质产生了免疫反应，这种影响随着每次男性怀孕而变得更有可能，并被认为会导致一些后来出生的男性的大脑发育发生变化。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会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被男性吸引，而不是女性。*我们最近通过检测同性恋男性的母亲，特别是那些有前夫的男孩的母亲，是否对Y染色体编码的两种蛋白质产生免疫反应(相对于异性恋儿子的母亲)来检验这一假设，这两种蛋白质对男性大脑发育起着重要作用。我们开发了针对这些蛋白质的免疫分析，并检测了大约130名有儿子的母亲的部分血液样本，其中约一半有同性恋儿子，以及额外的对照样本(例如，没有男孩的妇女)。结果显示，同性恋儿子的母亲，特别是那些有过(异性恋)儿子的母亲，比起异性恋儿子的母亲，对这些蛋白质中的一种有明显的免疫反应。*在下一个资助期，我将完成对参与者一部分血液(记忆B细胞)的第二次测试，这些血液(记忆B细胞)尚未进行测试。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。我预计这项工作将证实我们早先的发现。我还计划检查其他性取向变异男孩的母亲的样本，例如，性别焦虑症男孩，尽管对童年时的生物性别不满意，但长大后很可能是同性恋，但成年后不会表现出明显的变性者。我还将研究无性恋男性的母亲的这些影响，无性恋者是那些对他人没有吸引力的人。无性恋男性也有FBO效应，这增加了这样一种可能性，即对他人的基本性吸引机制受到Y-连锁蛋白的影响，母体对这些蛋白的免疫反应可能会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性之一(FBO)，而且还提供了直接证据，证明了性取向背后的特定生物机制：母体对一种Y连接蛋白的免疫反应，该蛋白对男性胎儿大脑发育至关重要。