Thirteen Ovary-Enriched Genes Are Individually Not Essential for Female Fertility in Mice

Author:

Pham Anh Hoang12,Emori Chihiro1ORCID,Ishikawa-Yamauchi Yu34ORCID,Tokuhiro Keizo5ORCID,Kamoshita Maki1ORCID,Fujihara Yoshitaka16ORCID,Ikawa Masahito1247ORCID

Affiliation:

1. Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan

2. Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan

3. Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama 236-0027, Japan

4. The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan

5. Department of Genome Editing, Institute of Biomedical Science, Kansai Medical University, Osaka 573-1191, Japan

6. Department of Advanced Medical Technologies, National Cerebral and Cardiovascular Center, Osaka 564-8565, Japan

7. Center for Infectious Disease Education and Research, Osaka University, Osaka 565-0871, Japan

Abstract

Infertility is considered a global health issue as it currently affects one in every six couples, with female factors reckoned to contribute to partly or solely 50% of all infertility cases. Over a thousand genes are predicted to be highly expressed in the female reproductive system and around 150 genes in the ovary. However, some of their functions in fertility remain to be elucidated. In this study, 13 ovary and/or oocyte-enriched genes (Ccdc58, D930020B18Rik, Elobl, Fbxw15, Oas1h, Nlrp2, Pramel34, Pramel47, Pkd1l2, Sting1, Tspan4, Tubal3, Zar1l) were individually knocked out by the CRISPR/Cas9 system. Mating tests showed that these 13 mutant mouse lines were capable of producing offspring. In addition, we observed the histology section of ovaries and performed in vitro fertilization in five mutant mouse lines. We found no significant anomalies in terms of ovarian development and fertilization ability. In this study, 13 different mutant mouse lines generated by CRISPR/Cas9 genome editing technology revealed that these 13 genes are individually not essential for female fertility in mice.

Funder

Ministry of Education, Culture, Sports, Science and Technology (MEXT)/Japan Society for the Promotion of Science (JSPS) KAKENHI

Kansai Medical University Molecular Imaging Center of Diseases

Takeda Foundation

Publisher

MDPI AG

Reference34 articles.

1. Fertility and infertility: Definition and epidemiology;Wyns;Clin. Biochem.,2018

2. World Health Organization (2023). Infertility Prevalence Estimates: 1990–2021, WHO.

3. Walker, M.H., and Tobler, K.J. (2022). StatPearls [Internet], StatPearls Publishing. Updated 19 December 2022.

4. (1992). Recent Advances in Medically Assisted Conception, WHO. Report of a WHO Scientific Group.

5. Diagnosis and treatment of unexplained infertility;Quaas;Rev. Obstet. Gynecol.,2008

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