Open AccessLoss of ESRP1 blocks mouse oocyte development and leads to female infertility
Author(s) -
Luping Yu,
Huiru Zhang,
Xuebing Guan,
Dongdong Qin,
Jian Zhou,
Xin Wu
Publication year - 2020
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.196931
Subject(s) - biology , oocyte , microbiology and biotechnology , rna splicing , genetics , germline , gene , rna , embryo
Alternative splicing (AS) contributes to gene diversification, but AS program during germline development remains largely undefined. Here, we interrupted pre-mRNA splicing events controlled by epithelial splicing regulatory protein 1 (ESRP1) and found that it induced female infertility in mice. Esrp1 deletion perturbed spindle organization, chromosome alignment, and metaphase-to-anaphase transformation in oocytes. The first polar body extrusion (PBE) was blocked during oocyte meiosis due to abnormal activation of spindle assembly checkpoint (SAC) and insufficiency of anaphase-promoting complex/cyclosome (APC/C) in Esrp1-knockout oocytes. Esrp1-knockout hampered follicular development and ovulation; eventually, premature ovarian failure (POF) occurred in six-month-old Esrp1-knockout mouse. Using single-cell RNA sequencing analysis, 528 aberrant AS events of maternal mRNA transcripts were revealed and were preferentially associated with microtubule cytoskeletal organization. Notably, we found that loss of ESRP1 disturbed a comprehensive set of gene-splicing sites—including those within Trb53bp1, Rac1, Bora, Kif2c, Kif23, Ndel1, Kif3a, Cenpa, and Lsm14b—that potentially caused abnormal spindle organization. Collectively, our findings provide the first report elucidating the ESRP1- mediated AS program of maternal mRNA transcripts, may contribute to oocyte meiosis and female fertility in mice.