Serum Response Factor Cooperates With Progesterone Receptor to Regulate Oviductal Smooth Muscle Gene Expression...

The oviduct (fallopian tube) houses the site of fertilization and transports embryos to the uterus for on-time implantation. Hormone-regulated contractions of the oviductal smooth muscle (myosalpinx) are thought to participate in this process. Serum response factor (SRF) is a widely expressed transcription factor shown to facilitate smooth muscle development as well as murine oviductal function. Our past work in the uterus has suggested that SRF transcriptional activity is associated with the master pregnancy regulator progesterone receptor (PGR). We therefore hypothesized that SRF and PGR work together to influence oviductal gene expression. Ablation of Srf in the Pgr-expressing cells of the mouse oviduct resulted in extensive transcriptomic consequences. Of 1670 differentially expressed genes in the Srf-deficient oviduct, 306 also contained an SRF binding region within 10 kb of the TSS, including cytoskeletal, contractile, and extracellular matrix genes important for muscle structure and function. Histological analysis confirmed disruption of the smooth muscle layer in the Srf-deficient oviduct, and functional contractility analyses demonstrated that contractile activity was deficient and irregular. Comparative transcriptomic analysis of oviducts deficient in smooth muscle Pgr expression uncovered parallel downregulation of extracellular matrix organization pathways and smooth muscle contraction processes. Integration of SRF and PGR cistromic analyses identified a set of structural and contractile smooth muscle genes co-occupied and co-regulated by SRF and PGR including Myh11, Actg2, and Des. Our findings highlight a prominent regulatory mechanism for SRF and PGR in the oviduct, disruption of which contributes to impaired myosalpinx function and infertility.