Abstract
We previously identified solute carrier 22a14 (Slc22a14) as a spermatogenesis-associated transmembrane protein in mice. Although Slc22a14 is a member of the organic anion/cation transporter family, its expression profile and physiological role have not been elucidated. Here, we show that Slc22a14 is crucial for sperm motility and male fertility in mice. Slc22a14 is expressed specifically in male germ cells, and mice lacking the Slc22a14 gene show severe male infertility. Although the overall differentiation of sperm was normal, Slc22a14−/− cauda epididymal spermatozoa showed reduced motility with abnormal flagellar bending. Further, the ability to migrate into the female reproductive tract and fertilise the oocyte were also impaired in Slc22a14−/− spermatozoa. The abnormal flagellar bending was thought to be partly caused by osmotic cell swelling since osmotic challenge or membrane permeabilisation treatment alleviated the tail abnormality. In addition, we found structural abnormalities in Slc22a14−/− sperm cells: the annulus, a ring-like structure at the mid-piece–principal piece junction, was disorganised, and expression and localisation of septin 4, an annulus component protein that is essential for the annulus formation, was also impaired. Taken together, our results demonstrated that Slc22a14 plays a pivotal role in normal flagellar structure, motility and fertility in mouse spermatozoa.
Highlights
We previously identified solute carrier 22a14 (Slc22a14) as a spermatogenesis-associated transmembrane protein in mice
Defects in Solute carrier (SLC) functioning are closely associated with human diseases[2,3] such as glucose/galactose malabsorption[4], familial renal glucosuria[5] and amyotrophic lateral sclerosis[6]
We examined the change of expression of Slc22a14 during the first wave of spermatogenesis and found that it began to be expressed in testes at 25 days of age (Fig. 1c)
Summary
We previously identified solute carrier 22a14 (Slc22a14) as a spermatogenesis-associated transmembrane protein in mice. Slc22a14 is a member of the organic anion/cation transporter family, its expression profile and physiological role have not been elucidated. To understand the molecular basis for sperm differentiation and function and to find potential targets for fertility drugs, we previously screened for spermatogenesis-associated transmembrane protein genes in mice[8] and identified 53 genes, including Slc22a14, a member of the Slc[22] transporter subfamily. Each member selectively transports organic anions or organic cations where they usually show broad substrate specificity, at least in vitro, with varying affinity Experimental evidence of their physiological function has been accumulated for some members of the Slc[22] family. Slc22a1-deficient mice are viable, fertile and healthy, liver uptake and direct intestinal excretion of substrate organic cations is impaired[12]. Only limited information has been provided regarding Slc22a14 so far
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