INRS-Institut Armand-Frappier and BioMed research Center, Université du Québec, Laval, QC, Canada.
J Pineal Res. 2015 Aug;59(1):38-46. doi: 10.1111/jpi.12236. Epub 2015 Apr 20.
Melatonin is highly produced in the placenta where it protects against molecular damage and cellular dysfunction arising from hypoxia/re-oxygenation-induced oxidative stress as observed in primary cultures of syncytiotrophoblast. However, little is known about melatonin and its receptors in the human placenta throughout pregnancy and their role in villous trophoblast development. The purpose of this study was to determine melatonin-synthesizing enzymes, arylalkylamine N-acetyltransferase (AANAT) and hydroxyindole O-methyltransferase (HIOMT), and melatonin receptors (MT1 and MT2) expression throughout pregnancy as well as the role of melatonin and its receptors in villous trophoblast syncytialization. Our data show that the melatonin generating system is expressed throughout pregnancy (from week 7 to term) in placental tissues. AANAT and HIOMT show maximal expression at the 3rd trimester of pregnancy. MT1 receptor expression is maximal at the 1st trimester compared to the 2nd and 3rd trimesters, while MT2 receptor expression does not change significantly during pregnancy. Moreover, during primary villous cytotrophoblast syncytialization, MT1 receptor expression increases, while MT2 receptor expression decreases. Treatment of primary villous cytotrophoblast with an increasing concentration of melatonin (10 pM-1 mM) increases the fusion index (syncytium formation; 21% augmentation at 1 mM melatonin vs. vehicle) and β-hCG secretion (121% augmentation at 1 mM melatonin vs. vehicle). This effect of melatonin appears to be mediated via its MT1 and MT2 receptors. In sum, melatonin machinery (synthetizing enzymes and receptors) is expressed in human placenta throughout pregnancy and promotes syncytium formation, suggesting an essential role of this indolamine in placental function and pregnancy well-being.
褪黑素在胎盘组织中大量产生，可保护其免受缺氧/再氧化诱导的氧化应激引起的分子损伤和细胞功能障碍，这在合体滋养层原代培养中得到了观察。然而，关于褪黑素及其受体在整个孕期的人类胎盘组织中的表达及其在绒毛滋养层发育中的作用，人们知之甚少。本研究的目的是确定褪黑素合成酶、芳基烷基胺 N-乙酰转移酶（AANAT）和羟基吲哚 O-甲基转移酶（HIOMT）以及褪黑素受体（MT1 和 MT2）在整个孕期的表达，以及褪黑素及其受体在绒毛滋养层融合中的作用。我们的数据表明，褪黑素生成系统在胎盘组织中整个孕期（从第 7 周到足月）表达。AANAT 和 HIOMT 在妊娠晚期表达最高。MT1 受体的表达在孕早期最高，而在孕中期和孕晚期则较低，而 MT2 受体的表达在整个孕期没有明显变化。此外，在原代绒毛滋养层细胞融合过程中，MT1 受体的表达增加，而 MT2 受体的表达减少。用不同浓度的褪黑素（10 pM-1 mM）处理原代绒毛滋养层细胞可增加融合指数（合胞体形成；1 mM 褪黑素组比载体组增加 21%）和β-hCG 分泌（1 mM 褪黑素组比载体组增加 121%）。褪黑素的这种作用似乎是通过其 MT1 和 MT2 受体介导的。总之，褪黑素的产生机制（合成酶和受体）在整个孕期的人胎盘组织中表达，并促进合胞体形成，表明这种吲哚胺在胎盘功能和妊娠健康中起着重要作用。
