{"title":"Ccdc152 is not necessary for male fertility, but contributes to maintaining sperm morphology.","authors":"Ryua Harima, Takahiro Sasaki, Takayuki Kaneko, Fuka Aso, Hayato Takashima, Takashi Toyama, Kenshiro Hara, Kentaro Tanemura, Yoshiro Saito","doi":"10.1262/jrd.2024-058","DOIUrl":null,"url":null,"abstract":"<p><p>Selenoprotein P (SeP) is synthesized in the liver and plays a vital role in maintaining selenium homeostasis via transport throughout the body. Previous studies have shown that SeP-deficient mice have severely reduced expression of selenoproteins essential for testicular function, leading to male infertility. We previously reported that the high expression of Ccdc152 in hepatocytes acts as a lncRNA, suppressing SeP expression in the liver. Ccdc152 reduces SeP translation by binding to SeP mRNA and decreasing its interaction with SECIS-binding protein 2. Although Ccdc152 is highly expressed in testes, its function remains unclear. Therefore, this study aimed to elucidate the role of Ccdc152 in the testes. Using the CRISPR/Cas9 system, we generated mice lacking all exons of Ccdc152 and found that SeP expression levels in the liver and plasma, as well as overall selenium homeostasis, remained unchanged. No significant differences were observed in the expression of glutathione peroxidase 1/4 or level of selenium in the testes. Subsequent investigation of the impact on male reproductive function revealed no abnormalities in sperm motility or Mendelian ratios of the offspring. However, a slight decrease in testicular weight and an increased rate of sperm malformations in the epididymis were observed. RNA-seq and pathway analyses identified the reduced expression of multiple genes related to kinesin and reproductive pathways. Based on these findings, Ccdc152 may not be essential for male reproductive function, but it may enhance reproductive capabilities by maintaining the expression of genes necessary for reproduction.</p>","PeriodicalId":16942,"journal":{"name":"Journal of Reproduction and Development","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Reproduction and Development","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1262/jrd.2024-058","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"AGRICULTURE, DAIRY & ANIMAL SCIENCE","Score":null,"Total":0}
引用次数: 0
Abstract
Selenoprotein P (SeP) is synthesized in the liver and plays a vital role in maintaining selenium homeostasis via transport throughout the body. Previous studies have shown that SeP-deficient mice have severely reduced expression of selenoproteins essential for testicular function, leading to male infertility. We previously reported that the high expression of Ccdc152 in hepatocytes acts as a lncRNA, suppressing SeP expression in the liver. Ccdc152 reduces SeP translation by binding to SeP mRNA and decreasing its interaction with SECIS-binding protein 2. Although Ccdc152 is highly expressed in testes, its function remains unclear. Therefore, this study aimed to elucidate the role of Ccdc152 in the testes. Using the CRISPR/Cas9 system, we generated mice lacking all exons of Ccdc152 and found that SeP expression levels in the liver and plasma, as well as overall selenium homeostasis, remained unchanged. No significant differences were observed in the expression of glutathione peroxidase 1/4 or level of selenium in the testes. Subsequent investigation of the impact on male reproductive function revealed no abnormalities in sperm motility or Mendelian ratios of the offspring. However, a slight decrease in testicular weight and an increased rate of sperm malformations in the epididymis were observed. RNA-seq and pathway analyses identified the reduced expression of multiple genes related to kinesin and reproductive pathways. Based on these findings, Ccdc152 may not be essential for male reproductive function, but it may enhance reproductive capabilities by maintaining the expression of genes necessary for reproduction.
期刊介绍:
Journal of Reproduction and Development (JRD) is the
official journal of the Society for Reproduction and Development,
published bimonthly, and welcomes original articles. JRD
provides free full-text access of all the published articles on
the web. The functions of the journal are managed by Editorial
Board Members, such as the Editor-in-Chief, Co-Editor-inChief, Managing Editors and Editors. All manuscripts are
peer-reviewed critically by two or more reviewers. Acceptance
is based on scientific content and presentation of the materials.
The Editors select reviewers and correspond with authors. Final
decisions about acceptance or rejection of manuscripts are made
by the Editor-in-Chief and Co-Editor-in-Chief.