Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, People's Republic of China.
NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 201203, People's Republic of China.
Int J Biol Sci. 2022 Jan 1;18(3):1150-1170. doi: 10.7150/ijbs.68335. eCollection 2022.
In some cases of spontaneous miscarriage (SM), the exact etiology cannot be determined. Autophagy, which is responsible for cellular survival under stress conditions, has also been implicated in many diseases. Recently, it is also surmised to be correlated with SM. However, the detailed mechanism remains elusive. In fact, there are several essential steps during pregnancy establishment and maintenance: trophoblasts invasion, placentation, decidualization, enrichment and infiltration of decidua immune cells (e.g., natural killer, macrophage and T cells). Accordingly, upstream molecules and downstream effects of autophagy are discussed in these processes, respectively. Of note, autophagy regulates the crosstalk between these cells at the maternal-fetal interface as well. Aberrant autophagy is found in villi, decidual stromal cells, peripheral blood mononuclear cells in SM patients, although the findings are inconsistent among different studies. Furthermore, potential treatments targeting autophagy are included, during which rapamycin and vitamin D are hot-spots in recent literatures. To conclude, a moderately activated autophagy is deeply involved in pregnancy, suggesting that autophagy should be a regulator and promising target for treating SM.
在某些自然流产 (SM) 的情况下,确切的病因无法确定。自噬负责在应激条件下维持细胞存活,也与许多疾病有关。最近,它也被推测与 SM 有关。然而,其详细的机制仍不清楚。事实上,妊娠建立和维持有几个重要的步骤:滋养细胞浸润、胎盘形成、蜕膜化、蜕膜免疫细胞(如自然杀伤细胞、巨噬细胞和 T 细胞)的富集和浸润。因此,分别讨论了自噬在这些过程中的上游分子和下游效应。值得注意的是,自噬还调节母体-胎儿界面这些细胞之间的串扰。SM 患者的绒毛、蜕膜基质细胞、外周血单个核细胞中存在异常的自噬,尽管不同研究的结果不一致。此外,还包括针对自噬的潜在治疗方法,其中雷帕霉素和维生素 D 是最近文献中的热点。总之,适度激活的自噬深深参与妊娠,提示自噬可能是治疗 SM 的调节剂和有前途的靶点。