CIB4 is essential for the haploid phase of spermatogenesis in mice†

Abstract

Spermatogenesis is a complex developmental process that involves the proliferation of diploid cells, meiotic division, and haploid differentiation. Many genes are shown to be essential for male fertility using knockout (KO) mice; however, there still remain genes to be analyzed to elucidate their molecular mechanism and their roles in spermatogenesis. Calcium- and integrin-binding protein 1 (CIB1) is a ubiquitously expressed protein that possesses three paralogs: CIB2, CIB3, and CIB4. It is reported that Cib1 KO male mice are sterile due to impaired haploid differentiation. In this study, we discovered that Cib4 is expressed strongly in mouse and human testis and begins expression during the haploid phase of spermatogenesis in mice. To analyze the function of CIB4 in vivo, we generated Cib4 KO mice using the CRISPR/Cas9 system. Cib4 KO male mice are sterile due to impaired haploid differentiation, phenocopying Cib1 KO male mice. Spermatogenic cells isolated from seminiferous tubules demonstrate an essential function of CIB4 in the formation of the apical region of the sperm head. Further analysis of CIB4 function may shed light on the etiology of male infertility caused by spermatogenesis defects, and CIB4 could be a target for male contraceptives because of its dominant expression in the testis. Summary sentence Cib4 mutant mice exhibit male infertility due to impaired spermiogenesis.

Single-cell transcriptome analysis and in vitro differentiation of testicular cells reveal novel insights into male sterility of the interspecific hybrid cattle-yak

“…To sec. SPC [ 12 , 35 , 36 ]. Furthermore, we observed the upregulation of genes associated with early spermatid development ( TJP3 , TEX29 and SAXO1 ), acrosomal vesicle components ( ACRV1 ), fertilization ( PLCZ1 ) and spermatid chromatin remodeling ( TXNDC8 and CHD5 ) [ 37 – 39 ] in early SPT.…”

Transcriptome Studies Reveal the N6-Methyladenosine Differences in Testis of Yaks at Juvenile and Sexual Maturity Stages

“…Enrichment analysis revealed that DMRs were involved in major male reproductive processes, including the development of testicular seminiferous tubules, spermatogonial differentiation, and meiosis. In addition, CIB2 , AK1 , FOXJ2 , PKDREJ , SLC9A3 , and TOPAZ1 genes in the hypermethylated DMRs were specifically expressed in spermatocytes and round sperm cells, regulating spermatogenesis [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. In hypomethylated DMRs, it was found that BCL6 is associated with cell apoptosis [ 46 , 47 ], EPHA2 regulates self-renewal of SSCs [ 48 , 49 ], TAF12 regulates the transcription program of specific genes in the testes [ 50 , 51 ].…”

Genome-Wide Association Studies, Runs of Homozygosity Analysis, and Copy Number Variation Detection to Identify Reproduction-Related Genes in Bama Xiang Pigs

“…Gene CIB4 , which is strongly expressed in mouse and human testes, plays an essential role in the spermatid head. Gene CIB4 knockout (KO) mice are sterile because haploid differentiation becomes impaired ( 33 ). Knocking out the DRC1 gene in mice completely disorders the axoneme structure of sperm flagella, impairing sperm motility ( 34 ).…”