The disruption of CDK8/19-mediated regulation of other transcription factors and signaling pathways could indeed contribute to the infertility phenotype observed in DKO mice beyond the effects on steroidogenesis. CDK8/19 are known to regulate the transcriptional activity of various signaling pathways and transcription factors, impacting multiple cellular processes beyond steroidogenesis. Here are some ways in which the disruption of CDK8/19-mediated regulation could contribute to infertility:
Transcriptional regulation: CDK8/19 are involved in the regulation of transcription factors that control key genes essential for spermatogenesis. Disruption of this regulatory function could lead to dysregulation of gene expression patterns critical for germ cell development, meiosis progression, and sperm maturation.
Cell cycle control: CDK8/19 play a role in cell cycle regulation and progression. The loss of CDK8/19 could affect the cell cycle dynamics in spermatogenic cells, leading to cell cycle arrest, apoptosis, or aberrant differentiation, all of which can impact fertility.
Signaling pathways: CDK8/19 are implicated in various signaling pathways that are crucial for male reproductive function. Disruption of these pathways could affect hormone signaling, cell-cell communication, and developmental processes necessary for spermatogenesis and male fertility.
Epigenetic regulation: CDK8/19 have been linked to epigenetic modifications and chromatin remodeling, which are essential for proper gene expression during spermatogenesis. Alterations in epigenetic regulation due to the loss of CDK8/19 could impact the differentiation and maturation of germ cells.
In conclusion, the disruption of CDK8/19-mediated regulation of transcription factors and signaling pathways can have broad implications for male fertility beyond steroidogenesis. The multifaceted roles of CDK8/19 in gene expression, cell cycle control, signaling, and epigenetic regulation highlight the complexity of their contribution to spermatogenesis and reproductive function.