Int J Biol Sci 2022; 18(3):1150-1170. doi:10.7150/ijbs.68335 This issue


Insight of Autophagy in Spontaneous Miscarriage

Xue-Yun Qin1,2, Hui-Hui Shen1, Wen-Jie Zhou3, Jie Mei4, Han Lu5, Xiao-Fang Tan6, Rui Zhu7, Wen-Hui Zhou8, Da-Jin Li1, Tao Zhang9, Jiang-Feng Ye10, Ming-Qing Li1,2,11,✉

1. Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, People's Republic of China
2. NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 201203, People's Republic of China
3. Center of Reproductive Medicine of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China
4. Reproductive Medicine Centre, Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medicine School, Nanjing, 210000, People's Republic of China
5. Departments of Assisted Reproduction, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, People's Republic of China
6. Reproductive Medicine Centre, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong, 226006, People's Republic of China
7. Center for Human Reproduction and Genetics, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou 215002, People's Republic of China
8. Medicine Centre for Human Reproduction, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People's Republic of China
9. Assisted Reproductive Technology Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, People's Republic of China
10. Division of Obstetrics and Gynecology, KK Women's and Children's Hospital, 229899, Singapore
11. Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200080, People's Republic of China

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Qin XY, Shen HH, Zhou WJ, Mei J, Lu H, Tan XF, Zhu R, Zhou WH, Li DJ, Zhang T, Ye JF, Li MQ. Insight of Autophagy in Spontaneous Miscarriage. Int J Biol Sci 2022; 18(3):1150-1170. doi:10.7150/ijbs.68335. Available from

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Graphic abstract

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.

Keywords: autophagy, spontaneous miscarriage, trophoblast cells, placentation, decidualization, decidual immune cells