Discovery Shed New Light on Male Infertility
Researchers at The Chinese University of Hong Kong have made another big step forward in the study of male fertility with the discovery that an epithelial ion channel, the defect of which has been previously shown to result in female infertility, was also present in sperm and affecting male fertility. The finding was published online in the recent issue of the highly reputable Proceedings of National Academy of Sciences of the United States of America.
Sperm are not able to fertilize the egg unless they go through an activation process named capacitation, which is known to be stimulated by bicarbonate. The research team of Prof Chan Hsiao Chang, Director of the Epithelial Cell Biology Research Centre, in collaboration with Zhejiang Academy of Medical Sciences, demonstrated that Cystic fibrosis transmembrane conductance regulator (CFTR) is involved in transporting bicarbonate into sperm, and thus, is vital to sperm fertilizing capacity and male fertility. CFTR is an anion channel, mutations of which cause cystic fibrosis, a disease characterized by defective Cl- and HCO3- transport with clinical manifestations in a number of organ systems. Previous studies by the centre have described the present of this channel in the female reproductive tract and its defect leads to impaired bicarbonate secretion that in turn, affects sperm fertilizing capacity.
While over 95% of CF male patients are infertile because of congenital bilateral absence of the vas deferens (CBAVD), the question whether CFTR mutations are involved in other forms of male infertility is under intense debates. The research team reported for the first time that CFTR is detected in both human and mouse sperm. CFTR inhibitor or antibody significantly reduces the sperm capacitation, and the associated HCO3–dependent events. They also found that the fertilizing capacity of the sperm obtained from heterozygous CFTR mutant mice is also significantly lower as compared to that of the wild-type.
These results suggest that CFTR in sperm may be involved in the transport of HCO3- important for sperm capacitation and that CFTR mutations with impaired CFTR function may lead to reduced sperm fertilizing capacity and male infertility other than CBAVD. The present finding also suggests that defects in CFTR may affect male fertility to various degrees since near 2000 mutations have been found to be associated with CFTR. The present finding may explain many unexplained cases of male infertility and provide new target for diagnosis.