CTCF contributes in a critical way to spermatogenesis and male fertility

Abstract

The CCCTC-binding factor (CTCF) is an architectural protein that governs chromatin organization and gene expression in somatic cells. Here, we show that CTCF regulates chromatin compaction necessary for packaging of the paternal genome into mature sperm. Inactivation of Ctcf in male germ cells in mice (Ctcf-cKO mice) resulted in impaired spermiogenesis and infertility. Residual spermatozoa in Ctcf-cKO mice displayed abnormal head morphology, aberrant chromatin compaction, impaired protamine 1 incorporation into chromatin and accelerated histone depletion. Thus, CTCF regulates chromatin organization during spermiogenesis, contributing to the functional organization of mature sperm.

Male fertility status is associated with DNA methylation signatures in sperm and transcriptomic profiles of bovine preimplantation embryos

“…In bull spermatozoa, a study by Hur et al [68] reported that the protein of KCK4 localizes to the equatorial region of acrosome reacted sperm, and that inhibitor of the K 2P channels reduces not only fertilization but also development of bovine and mouse embryos in vitro. Interestingly, a DMR was located in the CTCF gene, which has been associated with spermatogenesis and male fertility [70, 71]. The CTCF gene plays a critical role in genome-wide gene regulation and has roles in epigenetic reprogramming, gametogenesis and embryo development and is also associated with fertility, as reviewed by Franco et al [70].…”

“…The CTCF gene plays a critical role in genome-wide gene regulation and has roles in epigenetic reprogramming, gametogenesis and embryo development and is also associated with fertility, as reviewed by Franco et al [70]. Indeed, a study by Hernandez-Hernandez et al [71] reported that mice with a conditional knock-out of the CTCF gene had smaller testis and spermatogenesis was impacted as several males were infertile. Moreover, spermatozoa of the CTCF-conditional knock-out mice also demonstrated aberrant histone retention and disrupted chromatin compaction.…”

Sperm DNA methylation ofH19imprinted gene and male infertility

“…Hypomethylation of paternal allele is associated with inactivation of IGF2 and is the most relevant cause of Silver–Russell imprinting disorder (De Crescenzo et al., ). Moreover, CTCF mutations in male germ cells in mice are associated with impaired spermiogenesis and infertility (Hernandez‐Hernandez, Lilienthal, Fukuda, Galjar, & Hoog, ).…”

Not just heads and tails: The complexity of the sperm epigenome

“…The presence of CTCF at sequence motifs in accessible sperm DNA was confirmed via ChIP-seq experiments (16). CTCF has been found to be essential for normal spermiogenesis, sperm fertility, and histone retention in mature sperm (39). Genome-wide Hi-C mapping experiments have uncovered the presence of compartments, CTCF-mediated loops, and topologically associating domains in sperm chromatin similar to those found in somatic cell lines and embryonic stem cells (16,37).…”