Male homosexuality and maternal immune responsivity to the Y-linked protein NLGN4Y.
Male homosexuality and maternal immune responsivity to the Y-linked protein NLGN4Y.
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男性同性恋和对Y连锁蛋白NLGN4Y的母体免疫反应。
DOI：
10.1073/pnas.1705895114
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发表时间：
2018-01-09
影响因子：
11.1
通讯作者：
Blanchard R
中科院分区：
文献类型：
--
作者：
Bogaert AF;Skorska MN;Wang C;Gabrie J;MacNeil AJ;Hoffarth MR;VanderLaan DP;Zucker KJ;Blanchard R
平均而言，男同性恋者比异性恋者有更多的哥哥，这是性科学中的一个众所周知的发现。这一发现被称为兄弟出生顺序效应。人们之所以对性取向产生强烈的科学兴趣，是因为它是人类的一个基本特征，而且它的起源往往是相当大的社会争议的焦点。我们的研究是在理解男性性取向起源方面的一项重大进步，它为一种理论上但之前未被检验的生物机制提供了支持--一种对一种对男性胎儿大脑发育至关重要的蛋白质的母体免疫反应--并开始解释男性同性恋最可靠的关联之一：哥哥。我们对一种免疫学解释进行了直接测试，以解释同性恋男性比异性恋男性有更多哥哥的发现。这一解释假设，一些母亲会产生抗体，对抗一种对男性大脑发育至关重要的Y连接蛋白，而且随着每一次男性怀孕，这种影响变得越来越有可能，从而改变他们后来出生的儿子的性取向背后的大脑结构。针对大脑发育中两个重要的Y连接蛋白--原钙粘蛋白11 Y连接(PCDH11Y)和神经连接蛋白4 Y连接(NLGN4Y；异构体1和2)--进行了免疫分析。对有儿子的母亲(其中大约一半有同性恋儿子)和另外的对照组(没有儿子的女性，男性)的血浆进行了男性蛋白质特异性抗体的分析。结果表明，女性抗-NLGN4Y抗体水平显著高于男性。此外，在统计控制怀孕次数后，同性恋儿子的母亲，特别是有哥哥的母亲，抗NLGN4Y水平显著高于对照样本的女性，包括异性恋儿子的母亲。这些结果表明，母体对NLGN4Y的免疫反应与随后的男性后代的性取向之间存在关联。
Gay men have, on average, a greater number of older brothers than do heterosexual men, a well-known finding within sexual science. This finding has been termed the fraternal birth order effect. Strong scientific interest in sexual orientation exists because it is a fundamental human characteristic, and because its origins are often the focal point of considerable social controversy. Our study is a major advance in understanding the origins of sexual orientation in men by providing support for a theorized but previously unexamined biological mechanism—a maternal immune response to a protein important in male fetal brain development—and by beginning to explain one of the most reliable correlates of male homosexuality: older brothers. We conducted a direct test of an immunological explanation of the finding that gay men have a greater number of older brothers than do heterosexual men. This explanation posits that some mothers develop antibodies against a Y-linked protein important in male brain development, and that this effect becomes increasingly likely with each male gestation, altering brain structures underlying sexual orientation in their later-born sons. Immune assays targeting two Y-linked proteins important in brain development—protocadherin 11 Y-linked (PCDH11Y) and neuroligin 4 Y-linked (NLGN4Y; isoforms 1 and 2)—were developed. Plasma from mothers of sons, about half of whom had a gay son, along with additional controls (women with no sons, men) was analyzed for male protein-specific antibodies. Results indicated women had significantly higher anti-NLGN4Y levels than men. In addition, after statistically controlling for number of pregnancies, mothers of gay sons, particularly those with older brothers, had significantly higher anti-NLGN4Y levels than did the control samples of women, including mothers of heterosexual sons. The results suggest an association between a maternal immune response to NLGN4Y and subsequent sexual orientation in male offspring.
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影响因子：
--
作者：
Palmeira P;Quinello C;Silveira-Lessa AL;Zago CA;Carneiro-Sampaio M
通讯作者：
Carneiro-Sampaio M
影响因子：
2.9
作者：
Blanchard, R;Bogaert, AF
通讯作者：
Bogaert, AF
影响因子：
82.9
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影响因子：
3.8
作者：
Cantor, JM;Blanchard, R;Bogaert, AF
通讯作者：
Bogaert, AF
影响因子：
3.7
作者：
Chan, William F. N.;Gurnot, Cecile;Nelson, J. Lee
通讯作者：
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