Effects of early life adversity on male reproductive behavior and the medial preoptic area transcriptome
Effects of early life adversity on male reproductive behavior and the medial preoptic area transcriptome
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DOI：
10.1038/s41386-022-01282-9
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发表时间：
2022-01-31
影响因子：
7.6
通讯作者：
Bangasser, Debra A.
中科院分区：
文献类型：
--
作者：
Eck, Samantha R.;Palmer, Jamie L.;Bangasser, Debra A.
早年生活中的逆境可以改变人类的生殖发育，改变青春期开始和性活动的时间。早期逆境的一种常见形式是获得资源的机会有限。这种逆境可以使用有限的垫料/筑巢模型（LBN）在大鼠中建模，其中从幼仔出生后第2-9天起将母鼠和幼仔置于低资源环境中。我们的实验室以前发现，在LBN条件下饲养的成年雄性大鼠与对照雄性大鼠相比，血浆雌二醇水平升高。在女性中，LBN对血浆激素水平、青春期时间或发情周期持续时间没有影响。雌激素介导雄性生殖行为。因此，在这里，我们比较了成年男性暴露于LBN与对照住房的生殖行为。LBN男性获得了一套生殖行为（坐骑，插入，和射精）更快地比他们的控制同行超过3周的测试。然而，在男性中，LBN对青春期的开始或某些大脑区域的男性化没有影响，这表明LBN对青春期后雌二醇和生殖行为的影响。在雄性和雌性大鼠中，我们接下来使用RNA测序来表征LBN诱导的内侧视前区（mPOA）的转录变化，这是雄性生殖行为的基础。LBN产生性别特异性的基因表达改变，许多转录本显示出相反方向的变化。许多转录改变LBN在男性中调节雌二醇，激素的变化，在mPOA的分子变化。通路分析表明，LBN诱导的神经信号和免疫信号的变化，在男性和女性，分别。总的来说，这些研究揭示了新的神经生物学机制，早期生活逆境可以改变生殖策略。
Early life adversity can alter reproductive development in humans, changing the timing of pubertal onset and sexual activity. One common form of early adversity is limited access to resources. This adversity can be modeled in rats using the limited bedding/nesting model (LBN), in which dams and pups are placed in a low resource environment from pups' postnatal days 2-9. Our laboratory previously found that adult male rats raised in LBN conditions have elevated levels of plasma estradiol compared to control males. In females, LBN had no effect on plasma hormone levels, pubertal timing, or estrous cycle duration. Estradiol mediates male reproductive behaviors. Thus, here we compared reproductive behaviors in adult males exposed to LBN vs. control housing. LBN males acquired the suite of reproductive behaviors (mounts, intromissions, and ejaculations) more quickly than their control counterparts over 3 weeks of testing. However, there was no effect of LBN in males on puberty onset or masculinization of certain brain regions, suggesting LBN effects on estradiol and reproductive behaviors manifest after puberty. In male and female rats, we next used RNA sequencing to characterize LBN-induced transcriptional changes in the medial preoptic area (mPOA), which underlies male reproductive behaviors. LBN produced sex-specific alterations in gene expression, with many transcripts showing changes in opposite directions. Numerous transcripts altered by LBN in males are regulated by estradiol, linking hormonal changes to molecular changes in the mPOA. Pathway analysis revealed that LBN induced changes in neurosignaling and immune signaling in males and females, respectively. Collectively, these studies reveal novel neurobiological mechanisms by which early life adversity can alter reproductive strategies.