Absence of CDK12 in oocyte leads to female infertility

Transcriptional activity and gene expression are essential for the development of a mature, meiotically competent oocyte. We have found that the absence of cyclin-dependent kinase 12 (CDK12) in oocytes leads to complete female sterility, as there are no fully developed oocytes able to accomplish meiosis I in the ovaries. Mechanistically, CDK12 in growing oocytes controls POLII activity and maintenance of the physiological maternal transcriptome, which negatively affects protein synthesis that promotes further oocyte growth. In addition, disruption of oocyte development disrupts folliculogenesis, resulting in a premature failure phenotype without terminal folliculogenesis and ovulation. In summary, we have characterized a single master regulator of the oocyte transcriptional program and gene expression that is essential for oocyte growth and female fertility. Graphical Abstract