Melatonin has been shown to improve in vitro fertilization and offspring survival after bacterial infection, but its role in regulating maternal‐fetal communication during early pregnancy has not been investigated. Results of this study demonstrated expression of abundant melatonin receptors in conceptus and endometrium during early pregnancy. In gilts, expression of melatonin receptor 1A (MTNR1A or MT1 ) and melatonin receptor 1B (MTNR1B or MT2 ) increased in trophectoderm (Tr) and uterine luminal epithelium (LE) with advancing days during early pregnancy in a different manner. Melatonin increased proliferation and migration of porcine trophectoderm (pTr) cell, the percent pTr cells in the G2 phase of the cell cycle, and the expression of implantation‐related genes by pTr cells and endometrial luminal epithelium (pLE). Melatonin also attenuated the production of LPS‐induced pro‐inflammatory cytokines and tunicamycin‐induced endoplasmic reticulum (ER) stress‐sensing proteins. The expression of sirtuin 1 (SIRT1 ) as a potential target of melatonin increased between Days 9 and 14 of gestation. Co‐treatment with SIRT1 inhibitor EX527 and melatonin restored cell‐cell interactions through PI3K and MAPK signaling. Knockdown of SIRT1 decreased the expression of implantation‐related genes, as well as migration of pTr and pLE cells. The expression of microRNAs regulated by SIRT1 was suppressed in response to melatonin. Furthermore, melatonin significantly increased lipopolysaccharide (LPS)‐reduced fertilization and embryogenesis in zebrafish model. These results suggest that melatonin may improve the uterine‐conceptus interactions via the regulation of SIRT1 during early pregnancy.

中文翻译：

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褪黑激素通过在妊娠早期调节 SIRT1 来改善子宫 - 概念的相互作用。

褪黑激素已被证明可以改善细菌感染后的体外受精和后代存活率，但尚未研究其在早期妊娠期间调节母胎交流的作用。这项研究的结果表明，妊娠早期在孕体和子宫内膜中表达了丰富的褪黑激素受体。在小母猪中，褪黑激素受体 1A（MTNR1A或MT1）和褪黑激素受体 1B（MTNR1B或MT2）的表达) 在妊娠早期随着天数的增加，滋养外胚层 (Tr) 和子宫腔上皮 (LE) 以不同的方式增加。褪黑激素增加了猪滋养外胚层 (pTr) 细胞的增殖和迁移、细胞周期 G2 期 pTr 细胞的百分比以及 pTr 细胞和子宫内膜腔上皮 (pLE) 着床相关基因的表达。褪黑激素还减弱了 LPS 诱导的促炎细胞因子和衣霉素诱导的内质网 (ER) 应激感应蛋白的产生。Sirtuin 1 ( SIRT1 ) 作为褪黑激素的潜在靶标的表达在妊娠第 9 天和第 14 天之间增加。与 SIRT1 抑制剂 EX527 和褪黑激素共同治疗通过 PI3K 和 MAPK 信号恢复细胞间相互作用。击倒SIRT1降低着床相关基因的表达，以及 pTr 和 pLE 细胞的迁移。由 SIRT1 调节的 microRNA 的表达因褪黑激素而受到抑制。此外，褪黑激素显着​​增加了斑马鱼模型中脂多糖（LPS）减少的受精和胚胎发生。这些结果表明，褪黑激素可能通过在妊娠早期调节 SIRT1 来改善子宫 - 概念的相互作用。