CFTR is involved in mediating the bicarbonate entry important for sperm capacitation

Abstract

Hco HCO3− is one of the critical factors for sperm capacitation leading to the final acquisition of their fertilizing capacity. We hypothesize that sperm CFTR may be involved in mediating the HCO3− entry important for sperm capacitation and that defective CFTR may lead to impaired sperm fertilizing capacity resulting in infertility. This study tested this hypothesis using a cftr+/− knockout mice model in conjunction with immunostaining and Western blot, intracellular pH and membrane potential measurement. Immunostaining and Western blot results demonstrated the expression of CFTR in human and mouse sperm membrane. In vitro study showed that intracellular pH elevation during the process of capacitation was attenuated by CFTR inhibitor and antibody in a concentration dependent manner. Addition of HCO3− induced a hyperpolarizing current and this process can be inhibited by CFTR inhibitor. Furthermore, a decrease in percentage of capacitated sperm and reduced fertilization were observed in heterozygous cftr mouse as compared to wild type sperm. Overall, This study indicates CFTR is expressed in sperm and involved in mediating HCO3− transport, thus playing an important role in sperm capacitation. (Supported by Strategic program of The Chinese University of Hong Kong)