CHD7 in oocytes is essential for female fertility

Jie Cheng; Qian Dong; Yujia Lu; Liya Shi; Guangxin Yao; Chaojun Wang; Cheng Zhou; Zhaoming Zhou; Zhuxi Huang; Ziang Han; Ming Zhu; Weijun Feng

doi:10.21037/atm-22-609

CHD7 in oocytes is essential for female fertility

Ann Transl Med. 2022 Mar;10(5):260. doi: 10.21037/atm-22-609.

Authors

Jie Cheng^#^{1

2}, Qian Dong^#^{3

4}, Yujia Lu⁵, Liya Shi⁶, Guangxin Yao^{1

2}, Chaojun Wang^{1

2}, Cheng Zhou⁷, Zhaoming Zhou⁷, Zhuxi Huang⁵, Ziang Han⁵, Ming Zhu⁵, Weijun Feng⁵

Affiliations

¹ Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.
³ Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁴ Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁵ Institute of Pediatrics, Children's Hospital of Fudan University, Shanghai Key Laboratory of Medical Epigenetics, International Co-Laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
⁶ Department of Reproductive Medicine Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
⁷ Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

^# Contributed equally.

Abstract

Background: 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.

Methods: 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 (Gdf9-Cre:Chd7^f/f ) 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.

Results: In our study, we demonstrated that CHD7 has high expression throughout all developmental stages of the oocyte. We found that deletion of Chd7 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.

Conclusions: 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.

Keywords: Chromodomain helicase DNA-binding protein 7 (CHD7); fertility; folliculogenesis; oocyte; reproduction.