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  • Loss of ESRP1 blocks mouse oocyte development and leads to female infertility.

Loss of ESRP1 blocks mouse oocyte development and leads to female infertility.

Development (Cambridge, England) (2020-12-16)
Luping Yu, Huiru Zhang, Xuebing Guan, Dongdong Qin, Jian Zhou, Xin Wu
ABSTRACT

Alternative splicing (AS) contributes to gene diversification, but the 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 was blocked during oocyte meiosis owing to abnormal activation of spindle assembly checkpoint and insufficiency of anaphase-promoting complex/cyclosome in Esrp1-knockout oocytes. Esrp1-knockout hampered follicular development and ovulation; eventually, premature ovarian failure occurred in six-month-old Esrp1-knockout mouse. Using single-cell RNA-seq 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, which may contribute to oocyte meiosis and female fertility in mice.

MATERIALS
Product Number
Brand
Product Description

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Hyaluronidase from bovine testes, Type IV-S, powder, suitable for mouse embryo cell culture, 750-3000 units/mg solid
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DAPI, for nucleic acid staining
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M2 medium, With HEPES, without penicillin and streptomycin, liquid, sterile-filtered, suitable for mouse embryo cell culture
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Milrinone - CAS 78415-72-2 - Calbiochem, A cell-permeable, selective inhibitor of cGMP-inhibited phosphodiesterase (PDE III; IC₅₀ = 300 nM).
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Bovine Serum Albumin, heat shock fraction, lyophilized powder, essentially fatty acid free, ≥98% (agarose gel electrophoresis)