Chen Min, Shi Jia-Lu, Zheng Zi-Meng, Lin Zhi, Li Ming-Qing, Shao Jun
Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai, People's Republic of China.
NHC Key Laboratory of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai, People's Republic of China.
Reproduction. 2023 Sep 29;166(5):357-368. doi: 10.1530/REP-23-0224. Print 2023 Nov 1.
Autophagy is important for trophoblast cells at the maternal-fetal interface during early pregnancy. This study suggests that trophoblast cells can promote the autophagy under a regulation of the LPA/LPAR 1-NHE1 axis.
The autophagy of trophoblasts is necessary for developing and maintaining a healthy pregnancy. Autophagy dysfunction in trophoblast cells is linked to recurrent spontaneous abortion (RSA). However, the mechanism underlying trophoblast autophagy is unknown. In this study, we investigated the expression of autophagy-related genes in both normal and RSA villi. We also examined the production of LPA and LPAR1 in trophoblast cells during early pregnancy. We found that the activation of the LPA-LPAR1 axis triggered the autophagy of trophoblast cells and increased the expression of NHE1. Inhibition of NHE1 suppressed the autophagy in trophoblast cells and we confirmed that NHE1 regulates LPA production in trophoblast cells. Additionally, we found decreased expression of autophagy-related genes and LPAR1 in villi from RSA patients. These observations indicate that the LPA/LPAR1-NHE1 axis regulates the autophagy of trophoblast cells during pregnancy. Insufficient autophagy and poor expression of LPAR1 in trophoblast cells may result in the dysfunction of the trophoblasts and an increased risk of spontaneous abortion. Overall, our research elucidated that a positive LPA/LPAR1-NHE1 axis can promote the autophagy of trophoblast cells and the abnormal axis leads to the autophagy deficiency of trophoblast cells in recurrent spontaneous abortion.
自噬在妊娠早期母胎界面的滋养层细胞中很重要。本研究表明，滋养层细胞可在溶血磷脂酸（LPA）/溶血磷脂酸受体1（LPAR 1）-钠氢交换体1（NHE1）轴的调控下促进自噬。
滋养层细胞的自噬对于正常妊娠的发展和维持至关重要。滋养层细胞中的自噬功能障碍与复发性自然流产（RSA）有关。然而，滋养层细胞自噬的潜在机制尚不清楚。在本研究中，我们调查了正常和RSA绒毛中自噬相关基因的表达。我们还检测了妊娠早期滋养层细胞中LPA和LPAR1的产生。我们发现LPA-LPAR1轴的激活触发了滋养层细胞的自噬并增加了NHE1的表达。抑制NHE1可抑制滋养层细胞的自噬，并且我们证实NHE1调节滋养层细胞中LPA的产生。此外，我们发现RSA患者绒毛中自噬相关基因和LPAR1的表达降低。这些观察结果表明，LPA/LPAR1-NHE1轴在妊娠期间调节滋养层细胞的自噬。滋养层细胞中自噬不足和LPAR1表达不佳可能导致滋养层细胞功能障碍和自然流产风险增加。总体而言，我们的研究阐明了正向的LPA/LPAR1-NHE1轴可促进滋养层细胞的自噬，而异常的轴会导致复发性自然流产中滋养层细胞的自噬缺陷。
