Litter gender composition and sex affect maternal behavior and DNA methylation levels of the oprm1 gene in rat offspring.
Litter gender composition and sex affect maternal behavior and DNA methylation levels of the oprm1 gene in rat offspring.
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DOI：
10.3389/fpsyt.2011.00021
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发表时间：
2011
影响因子：
4.7
通讯作者：
Kosten TA
中科院分区：
文献类型：
--
作者：
Hao Y;Huang W;Nielsen DA;Kosten TA
母阿片受体由Oprm1基因编码，并参与母婴行为。啮齿动物坝舔雄性幼仔多于舔雌性幼仔在肛门生殖器区域。这种行为与后代的应激反应有关，而应激反应可能是由表观遗传变化介导的。我们假设母亲的行为可能会影响Oprm1基因的DNA甲基化水平，并表现出性别差异。为了进一步探讨母幼行为和DNA甲基化水平的性别差异，我们改变了大鼠的产仔性别组成（LGC）。在产后第1天，筛选出8只全公、全母或4只公/ 4只母幼崽。在PN4、7和10日，将一只水坝与一只小狗放在一个测试笼中，持续10分钟。与幼犬接触的潜伏期被确定为舔幼犬的肛门生殖器和其他身体部位的时间。其他行为的频率被制成表格。在PN35上，从不同的大脑区域获得样本。通过对亚硫酸处理过的DNA进行直接测序，测量了Oprm1启动子区域特定CpG位点的DNA甲基化。LGC和性别的相互作用与白天延迟到幼崽接触。单性雄鼠在PN4上潜伏期最长，单性雌鼠在PN10上潜伏期最长。在肛门生殖器和其他身体部位，雄性幼崽比雌性幼崽更容易被舔。性别差异还体现在其他行为上。LGC改变了单性大鼠海马中Oprm1特定CpG的DNA甲基化，且水平较高。在伏隔核中，单性雄性表现出高甲基化水平，在尾状壳核中也有这种趋势。结果证实并扩展了产妇护理的性别差异和适度的LGC效应。LGC和性别都对与成瘾、压力调节、动机和认知相关的大脑区域的Oprm1基因的DNA甲基化有持久的影响，这可能表明导致这些行为的性别差异的一个因素。
The mu-opioid receptor is encoded by the Oprm1 gene and contributes to mother–infant behaviors. Rodent dams lick male pups more than female pups in the anogenital region. This behavior is linked to stress responsivity in the offspring that may be mediated by epigenetic changes. We hypothesized that maternal behavior may affect DNA methylation levels of the Oprm1 gene and show sex differences. To further explore sex differences in mother–pup behaviors and DNA methylation levels, we altered the litter gender composition (LGC) of rats. Litters were culled to eight all male, all female, or four male/four female pups on postnatal (PN) day 1. On PN4, 7, and 10, a dam was placed in a test cage with a pup for a 10-min period. Latency to pup contact was determined as were times spent licking the anogenital and other body regions of the pup. Frequencies of other behaviors were tabulated. On PN35, samples from various brain regions were obtained. DNA methylation at specific CpG sites in the Oprm1 promoter region were measured by direct sequencing of bisulfite-treated DNA. LGC and sex interacted with day for latency to pup contact. Latencies were longest on PN4 for single-sex males and on PN10 for single-sex females. Dams licked male pups more than female pups in both the anogenital and other body areas. Sex differences were seen in other behaviors. LGC altered DNA methylation at specific CpG's of Oprm1 in hippocampus with higher levels in single-sex rats. In nucleus accumbens, single-sex males showed hypermethylation levels, a trend seen in caudate–putamen. Results confirm and extend sex differences in maternal care with modest LGC effects. That both LGC and sex have enduring effects on DNA methylation of the Oprm1 gene in brain regions associated with addiction, stress regulation, motivation, and cognition may suggest one factor that contributes to gender differences in these behaviors.