TMEM16A chloride channels in the female reproductive tract and their role in normal and dysfunctional pregnancy and labour

Female fertility relies heavily on the health of the oviduct and uterus. Each of these organs consist of a muscular tube lined by epithelial cells. In this review, we discuss the role of the TMEM16A chloride ion channel, expressed in the epithelial and smooth muscle cells in these organs, with a focus on function and dysfunction. In the oviduct, infection and endometriosis are major causes of infertility and TMEM16A plays a major role. Oviduct epithelial TMEM16A is also essential for egg and sperm health and for the process of fertilization, which takes place in the oviduct. The role of TMEM16A in uterine function has focussed on the smooth muscle component. TMEM16A plays a major role in determining the sustained plateau component of the action potential in human myometrium. The plateau sits at the chloride equilibrium potential of -25 to -30 mV and, at this potential, calcium channels are active, permitting calcium influx and contraction. TMEM16A expression doubles in human labour and this is associated with a major increase in plateau and hence contraction duration. This prolongation of calcium influx permits contraction amplitude and duration to increase and appears to be important for successful labour.