Species: mouse
Mutation name:
type: null mutation
fertility: infertile - ovarian defect
Comment: ////////////////// Sgpl1 deletion elevates S1P levels, contributing to NPR2 inactivity and p21 expression that block germ cell development Cell Death Dis. 2021 Jun 3;12(6):574. doi: 10.1038/s41419-021-03848-9. Authors Feifei Yuan # 1 2 , Zhijuan Wang # 2 , Yanli Sun 2 , Hongwei Wei 2 , Yanying Cui 2 , Zhanying Wu 1 2 , Chunyu Zhang 2 , Ke-Ping Xie 2 , Fengchao Wang 3 , Meijia Zhang 4 Affiliations 1 State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, 100193, Beijing, China. 2 Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, 510006, Guangzhou, China. 3 National Institute of Biological Sciences, 102206, Beijing, China. wangfengchao@nibs.ac.cn. 4 Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, 510006, Guangzhou, China. zhangmeijia@scut.edu.cn. # Contributed equally. PMID: 34083520 DOI: 10.1038/s41419-021-03848-9 Free article Abstract Sphingosine phosphate lyase 1 (SGPL1) is a highly conserved enzyme that irreversibly degrades sphingosine-1-phosphate (S1P). Sgpl1-knockout mice fail to develop germ cells, resulting in infertility. However, the molecular mechanism remains unclear. The results of the present study showed that SGPL1 was expressed mainly in granulosa cells, Leydig cells, spermatocytes, and round spermatids. Sgpl1 deletion led to S1P accumulation in the gonads. In the ovary, S1P decreased natriuretic peptide receptor 2 (NPR2) activity in granulosa cells and inhibited early follicle growth. In the testis, S1P increased the levels of cyclin-dependent kinase inhibitor 1A (p21) and apoptosis in Leydig cells, thus resulting in spermatogenesis arrest. These results indicate that Sgpl1 deletion increases intracellular S1P levels, resulting in the arrest of female and male germ cell development via different signaling pathways.