Melatonin-related genes expressed in the mouse uterus during early gestation promote embryo implantation
Melatonin-related genes expressed in the mouse uterus during early gestation promote embryo implantation
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妊娠早期小鼠子宫中表达的褪黑激素相关基因促进胚胎着床
DOI：
10.1111/jpi.12216
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发表时间：
2015-04-01
影响因子：
10.3
通讯作者：
Liu, Guoshi
中科院分区：
文献类型：
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作者：
He, Changjiu;Wang, Jing;Liu, Guoshi
褪黑素是一种优异的抗氧化剂，由于其受体介导和不依赖于受体的抗氧化作用，是调节女性生殖的重要分子。在这项研究中，我们研究了褪黑激素对小鼠模型早期妊娠的影响。在妊娠早期，子宫内褪黑激素限速酶 AANAT 的表达逐渐增加，而 MT2 褪黑激素受体仅在妊娠第 2 天表达，并且未检测到 MT1。基于这些发现，我们进行了褪黑激素注射实验，结果表明，15mg/kg褪黑激素显着提高了植入部位的数量和窝产仔数。此外，还收集了囊胚和子宫以鉴定褪黑激素的局部作用。在接受褪黑激素治疗的小鼠中，子宫内膜比对照小鼠更厚；褪黑激素还导致子宫腺体密度增加，子宫腺体指数（UGI）显着高于对照组。血清类固醇激素测量显示，在妊娠第 6 天（植入后），褪黑激素显着下调 E-2 水平，但对黄体酮没有明显影响。基因表达分析显示，褪黑激素显着上调 HB-EGF 的表达，HB-EGF 是参与着床的关键基因及其受体 ErbB1 在囊胚中的表达。此外，影响蜕膜反应和管腔细胞分化的重要基因PRA和通过白血病抑制因子（LIF）调节子宫的p53在褪黑激素治疗后均升高。这些数据表明褪黑激素及其 MT2 受体影响早期妊娠。外源褪黑素治疗可以改善小鼠胚胎植入和产仔数，这可能在人类生殖健康和畜牧业中具有重要应用。
Melatonin, a superior antioxidant, is an important molecule which regulates female reproduction due to its receptor-mediated and receptor-independent antioxidant actions. In this study, we investigated the effect of melatonin on early gestation in a mouse model. During early gestation, the expression of the melatonin's rate-limiting enzyme, AANAT, gradually increased - in the uterus while the MT2 melatonin receptor was only expressed at day 2 of gestation and no MT1 was detected. Based on these findings, we conducted a melatonin injection experiment which demonstrated that 15mg/kg melatonin significantly improved the number of implantation sites and the litter size. Also, the blastocyst and uterus were collected to identify the local action of melatonin. In the melatonin-treated mice, the endometrium was thicker than in the control mice; melatonin also caused an increase in density of uterine glands, and the uterine gland index (UGI) was significantly elevated over that of the control. Serum steroid hormone measurements revealed that at day 6 of gestation (postimplantation), melatonin significantly downregulated the E-2 level, with no obvious effects on progesterone. Gene expression assay revealed that melatonin significantly upregulated expression of HB-EGF, a crucial gene involved in implantation as well as its receptor ErbB1 in the blastocyst. In addition, PRA, an important gene which influences the decidual response and luminal cell differentiation, p53, which regulates uterine through leukaemia inhibitory factor (LIF), were both increased after melatonin treatment. These data suggest that melatonin and its MT2 receptor influence early gestation. Exogenous melatonin treatment can improve mouse embryo implantation and litter size, which may have important applications in human reproductive health and animal husbandry.