The heterozygous mutations of SLC26A8 are not the main actors but might
be the guest players for male infertility
Abstract
Male infertility has become a serious health and social problem
troubling approximately 15% of couples worldwide; however, the genetic
and phenotypic heterogeneity of human infertility poses a substantial
obstacle to effective diagnosis and therapy. A previous study reported
that heterozygous mutations in solute carrier family 26 member 8
(SLC26A8, NG_033897.1) were causatively linked to asthenozoospermia.
Interestingly, in our research, three deleterious heterozygous mutations
of SLC26A8 were separately detected in three unrelated patients who were
suffered from teratozoospermia. These three heterozygous mutations
resulted in the reduce of SLC26A8 expression in transfected cells, while
no disrupt expression of SLC26A8 was observed in sperm from the affected
individuals. Noticeably, two of the three SLC26A8 heterozygous mutations
detected in the patients were inherited from their fertile fathers.
Thus, we suggested that male infertility associated with SLC26A8
mutations should be involved in a recessive-inherited pattern,
considering the infertile homozygous Slc26a8 KO male mice. Given that
SLC26A8 heterozygous mutations were detected in the infertile patients,
and SLC26A8 is predominantly expressed in the various germ cells during
spermatogenesis, the heterozygous mutations in SLC26A8 may not be the
direct genetic cause but contribute to male infertility to a certain
degree.