CHD7 in oocytes is essential for female fertility

Chromodomain helicase DNA-binding protein 7 (CHD7), which is associated with CHARGE (Coloboma, Heart defect, Atresia choanae, Restricted growth, Genital hypoplasia and Ear abnormality) syndrome is an important regulator in many vital developmental processes. However, its role during oocyte developme...

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Published inAnnals of translational medicine Vol. 10; no. 5; p. 260
Main Authors Cheng, Jie, Dong, Qian, Lu, Yujia, Shi, Liya, Yao, Guangxin, Wang, Chaojun, Zhou, Cheng, Zhou, Zhaoming, Huang, Zhuxi, Han, Ziang, Zhu, Ming, Feng, Weijun
Format Journal Article
LanguageEnglish
Published China AME Publishing Company 01.03.2022
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Summary:Chromodomain helicase DNA-binding protein 7 (CHD7), which is associated with CHARGE (Coloboma, Heart defect, Atresia choanae, Restricted growth, Genital hypoplasia and Ear abnormality) syndrome is an important regulator in many vital developmental processes. However, its role during oocyte development remains unknown. We screened the Gene Expression Omnibus (GEO) database for expression levels of CHD7 during folliculogenesis. We generated a conditional knockout (cKO) mouse strain with oocyte-specific deletion of CHD7 ( ) using the Cre-loxP approach. Evaluation of follicle numbers and reproductive ability was then conducted. In addition, granulosa cell (GC) apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and cleaved caspase-3, using immunohistochemistry (IHC) and immunofluorescence (IF). GC proliferation was measured by Ki67 staining as evaluated by IHC. In our study, we demonstrated that CHD7 has high expression throughout all developmental stages of the oocyte. We found that deletion of in oocytes can cause infertility or sub-fertility in female mice and is associated with decreased follicle numbers at all stages. In addition, we found that GC apoptosis was significantly higher in cKO mice. To our knowledge, our study has been the first to show that CHD7 plays a specific role during oogenesis. Our findings provide new insights into CHD7-related infertility.
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Contributions: (I) Conception and design: J Cheng, Q Dong, W Feng; (II) Administrative support: G Yao, C Wang, W Feng; (III) Provision of study materials: L Shi, Z Huang, Z Han, M Zhu; (IV) Collection and assembly of data: J Cheng, Q Dong, Y Lu; (V) Data analysis and interpretation: J Cheng, Q Dong, C Zhou, Z Zhou; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
These authors contributed equally to this work.
ISSN:2305-5839
2305-5839
DOI:10.21037/atm-22-609