期刊
BIOLOGY OF REPRODUCTION
卷 -, 期 -, 页码 -出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/biolre/ioac086
关键词
ovary; ovarian reserve; oocyte; ubiquitin; endocrine; estrous; ovulation
资金
- University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core
- Eunice Kennedy Shriver NICHD [R24 HD102061]
- NICHD [1F31HD097933]
UCHL1 is highly expressed in developing oocytes and plays a crucial role in proper ovarian folliculogenesis, estrous cyclicity, and fertility in female mice. The deficiency of UCHL1 results in reduced litter numbers and sizes, altered folliculogenesis, morphologically abnormal oocytes, disrupted estrous cyclicity, and apparent endocrine dysfunction.
Ubiquitin C-terminal hydrolase L1 (UCHL1) is a de-ubiquitinating enzyme enriched in neuronal and gonadal tissues known to regulate the cellular stores of mono-ubiquitin and protein turnover. While its function in maintaining proper motor neuron function is well established, investigation into its role in the health and function of reproductive processes is only just beginning to be studied. Single-cell-sequencing analysis of all ovarian cells from the murine perinatal period revealed that Uchl1 is very highly expressed in the developing oocyte population, an observation which was corroborated by high levels of oocyte-enriched UCHL1 protein expression in oocytes of all stages throughout the mouse reproductive lifespan. To better understand the role UCHL1 may be playing in oocytes, we utilized a UCHL1-deficient mouse line, finding reduced number of litters, reduced litter sizes, altered folliculogenesis, morphologically abnormal oocytes, disrupted estrous cyclicity and apparent endocrine dysfunction in these animals compared to their wild-type and heterozygous littermates. These data reveal a novel role of UCHL1 in female fertility as well as overall ovarian function, and suggest a potentially essential role for the ubiquitin proteasome pathway in mediating reproductive health. Ubiquitin C-terminal hydrolase L1 (UCHL1) is required for proper ovarian folliculogenesis, estrous cyclicity, and fertility in the female mouse.
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