Effect of depletion of TCF23 on myometrium transcriptome profile during late pregnancy
TCF23 is a basic-helix-loop-helix transcription factor lacking a DNA binding domain with a C-terminal mediated inhibitory action. Tcf23 was significantly induced by progesterone but not estradiol in vitro and in vivo. To evaluate the biological role of Tcf23, we generated the Tcf23 knockout mouse. Although pregnant Tcf23 KO mice were able to maintain gestation until full term, a considerable proportion of KO females experienced delayed parturition, dystocia, and reduced litter outcomes, with a high incidence of resorption and fetal lethality. Morphological analysis of the pregnant uterus revealed aberrant disruption of both circular and longitudinal myometrial layers and disarrayed extracellular matrix at the conceptus sites in the KO mice. Transcriptome profile analysis of the KO myometrium demonstrated disruptions in cell adhesion, extracellular matrix (ECM), and gap junction signaling, indicating the crucial role of TCF23 in myometrial remodeling and preparation for contractility during late pregnancy. Altogether, our research highlights a novel cause for labor dysfunction mediated by loss of Tcf23 activity in murine uterine tissue. Overall design: To investigate the function of TCF23 in the myometrium contraction, we generated TCF23 knockout mice by CRISPR/Cas9 technology. We then isolated the myometrium tissue from pregnant mice at gestational day 19 and performed RNA-seq of 3 different animals of each genotype. We conducted comparative gene expression profiling by analyzing data obtained from RNA-seq.