The gonadal niche safeguards human fetal germline cell development following maternal SARS-CoV-2 infection

Shijun Shen; Mengting Wang; Xiaocui Li; Beiying Wang; Wei Hong; Wei Li; Ben Xu; Zhenxiang Guo; Ruichen Han; Shanru Yi; Zhiping Wu; Xiaoying He; Liping Wang; Qianshu Zhu; Guang Yang; Hong Wang; Qiaolin Deng; Jiayu Chen; Shaorong Gao; Cizhong Jiang; Rui Gao

doi:10.1016/j.xcrm.2024.101515

The gonadal niche safeguards human fetal germline cell development following maternal SARS-CoV-2 infection

Cell Rep Med. 2024 Apr 9:101515. doi: 10.1016/j.xcrm.2024.101515. Online ahead of print.

Authors

Shijun Shen¹, Mengting Wang², Xiaocui Li³, Beiying Wang⁴, Wei Hong⁴, Wei Li⁵, Ben Xu², Zhenxiang Guo², Ruichen Han², Shanru Yi², Zhiping Wu⁴, Xiaoying He⁴, Liping Wang⁵, Qianshu Zhu⁵, Guang Yang⁵, Hong Wang², Qiaolin Deng⁶, Jiayu Chen⁷, Shaorong Gao⁸, Cizhong Jiang⁹, Rui Gao¹⁰

Affiliations

¹ Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education, Orthopedic Department of Tongji Hospital, Tongji University, Shanghai 200065, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China.
² Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China.
³ Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, China. Electronic address: lixiaocui@51mch.com.
⁴ Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, China.
⁵ Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education, Orthopedic Department of Tongji Hospital, Tongji University, Shanghai 200065, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China.
⁶ Department of Physiology and Pharmacology, Biomedicum B5, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, 17177 Stockholm, Sweden.
⁷ Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China. Electronic address: chenjiayu@tongji.edu.cn.
⁸ Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China. Electronic address: gaoshaorong@tongji.edu.cn.
⁹ Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education, Orthopedic Department of Tongji Hospital, Tongji University, Shanghai 200065, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China. Electronic address: czjiang@tongji.edu.cn.
¹⁰ Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China. Electronic address: gaorui@tongji.edu.cn.

PMID: 38631348
DOI: 10.1016/j.xcrm.2024.101515

Abstract

During pregnancy, germline development is vital for maintaining the continuation of species. Recent studies have shown increased pregnancy risks in COVID-19 patients at the perinatal stage. However, the potential consequence of infection for reproductive quality in developing fetuses remains unclear. Here, we analyze the transcriptome and DNA methylome of the fetal germline following maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We find that infection at early gestational age, a critical period of human primordial germ cell specification and epigenetic reprogramming, trivially affects fetal germ cell (FGC) development. Additionally, FGC-niche communications are not compromised by maternal infection. Strikingly, both general and SARS-CoV-2-specific immune pathways are greatly activated in gonadal niche cells to protect FGCs from maternal infection. Notably, there occurs an "in advance" development tendency in FGCs after maternal infection. Our study provides insights into the impacts of maternal SARS-CoV-2 infection on fetal germline development and serves as potential clinical guidance for future pandemics.

Keywords: COVID-19; SARS-CoV-2; developing fetus; germline cell; gonadal niche; host defense; human reproduction; immune response; pregnancy.