Gene changes may minimize masculinizing and defeminizing influences of exposure to male cotwins in female callitrichine primates.
Gene changes may minimize masculinizing and defeminizing influences of exposure to male cotwins in female callitrichine primates.
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DOI：
10.1186/s13293-016-0081-y
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发表时间：
2016
影响因子：
7.9
通讯作者：
Mickelberg J
中科院分区：
文献类型：
--
作者：
French JA;Frye B;Cavanaugh J;Ren D;Mustoe AC;Rapaport L;Mickelberg J
雌性哺乳动物的性别分化可以通过子宫内雄性胎仔的接近而改变，这种现象被称为宫内位置效应(IUP)。在猿类灵长类动物中，木犀草素(绒猴和罗望子素)很可能是IUP的候选对象，因为它们表现出专性的双卵双胞胎，并且胎儿在子宫内共享广泛的血管形成。在这篇文章中，我们确定了雌性生殖参数是否会因为与雄性双胞胎怀孕而改变，并评估了与抗缪勒和类固醇激素相关的基因在双胞胎长臂猿中的变化。我们评估了与雄性同卵双胞胎妊娠对雌性绒猴(Callithrix)和狮子Tamarins(Leontopithecus)繁殖性能和存活率的影响，并对比了怀孕一胎或多胎(M+)或没有雄性一胎(0M)的雌性。我们比较了双胞胎灵长类(Callithrix、Saguinus和Leontopithecus)与近缘的产生单胎的新大陆灵长类(Saimiri和Callimico)的性分化过程中涉及类固醇和反缪勒激素的基因的目标编码区。雌性Callitrichine灵长类没有IUP效应：M+和0M雌性之间的首次排卵年龄、平均产仔数、死胎比例和终生存活率没有差异。我们记录了与类固醇合成、运输和细胞活动相关的基因(SRD5A2、CYP19A1、SHBG和AR)以及与抗缪勒激素(AMH和AMHR2)相关的多个非同义替换。在唯一产生单个婴儿(Callimico)的Callitrichine(Callimico)中，有两个基因包含相对于双胞胎Callitrichine(CYP19A1和AMRHR2)的非同义替换；这些替换与非双胞胎Saimiri和人类相同，表明恢复到祖先序列。尽管在整个胚胎和胎儿发育过程中，与异性双胞胎共用胎盘血管，但与雌性双胞胎怀孕的雌性双胞胎相比，与雄性双胞胎怀孕的雌性马兜铃碱灵长类动物相比，生殖性能并没有下降。因此，宫内节育器对雌性生殖的影响不大。我们已经确定了与类固醇激素信号和代谢相关的候选基因的突变，特别是与AMH相关的基因，这些基因可能会改变骨钙素的蛋白质结构和功能。这些突变可能为女性提供保护，使其免受与男性双胞胎怀孕的男性化和去女性化的影响。本文的在线版本(doi：10.1186/s13293-0160081-y)包含补充材料，授权用户可以使用。
Sexual differentiation in female mammals can be altered by the proximity of male littermates in utero, a phenomenon known as the intrauterine position effect (IUP). Among simian primates, callitrichines (marmosets and tamarins) are likely candidates for IUP, since they exhibit obligate dizygotic twinning and fetuses share extensive vascularization in utero. In this paper, we determined whether female reproductive parameters are altered by gestating with a male twin and evaluated changes in genes associated with anti-Müllerian and steroid hormones in twinning callitrichine primates. We assessed the impact of gestation with male cotwins on reproductive performance and survivorship in female marmosets (Callithrix) and lion tamarins (Leontopithecus), contrasting measures for females gestated with one or more littermates (M+) or no male littermates (0M). We compared targeted coding regions for genes involved in steroidal and anti-Müllerian hormone mediation of sexual differentiation for representatives of twinning callitrichines (Callithrix, Saguinus, and Leontopithecus) with closely related New World primates that produce single births (Saimiri and Callimico). IUP effects in females were absent in female callitrichine primates: age at first ovulation, average litter size, and the proportion of stillborn infants, and lifetime survivorship did not differ between M+ and 0M females. We documented multiple nonsynonymous substitutions in genes associated with steroid synthesis, transport, and cellular action (SRD5A2, CYP19A1, SHBG, and AR) and with anti-Müllerian hormone (AMH and AMHR2) in callitrichines. In the only callitrichine to produce single infants (Callimico), two genes contained nonsynonymous substitutions relative to twinning callitrichines (CYP19A1 and AMRHR2); these substitutions were identical with nontwinning Saimiri and humans, suggesting a reversion to an ancestral sequence. In spite of a shared placental vasculature with opposite-sex twins throughout embryonic and fetal development, female callitrichine primates gestated with a male cotwin exhibit no decrement in reproductive performance relative to females gestated with female cotwins. Hence, IUP effects on female reproduction in callitrichines are modest. We have identified mutations in candidate genes relevant for steroid hormone signaling and metabolism, and especially in AMH-related genes, that are likely to alter protein structure and function in the callitrichines. These mutations may confer protection for females from the masculinizing and defeminizing influences of gestating with a male cotwin. The online version of this article (doi:10.1186/s13293-016-0081-y) contains supplementary material, which is available to authorized users.