CTCF contributes in a critical way to spermatogenesis and male fertility

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. Tunica albuginea of wild-type and Ctcf-cKO testis was removed and seminiferous tubules were transported to the lab bench in RNA stabilization reagent RNAlater (QIAGEN). RNA was extracted and purified with the RNeasy kit (QIAGEN). Three independent wild-type and four independent Ctcf-cKO microarray analysis were performed using the GeneChip mouse transcriptome assay 1.0 (Affimetrix)