A critical role of solute carrier 22a14 in sperm motility and male fertility in mice.
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.
Laboratory of Animal Physiology, Faculty of Agriculture, Shizuoka University, Shizuoka, Japan.
Shin-Ya
SY
Maruyama
Laboratory of Animal Physiology, Faculty of Agriculture, Shizuoka University, Shizuoka, Japan.
Momoe
M
Ito
Laboratory of Animal Physiology, Faculty of Agriculture, Shizuoka University, Shizuoka, Japan.
Yuusuke
Y
Ikami
Laboratory of Animal Physiology, Faculty of Agriculture, Shizuoka University, Shizuoka, Japan.
Yu
Y
Okitsu
Department of Reproductive Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Chizuru
C
Ito
Department of Reproductive Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Kiyotaka
K
Toshimori
Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
Wataru
W
Fujii
Laboratory of Animal Physiology, Faculty of Agriculture, Shizuoka University, Shizuoka, Japan.|Laboratory of Animal Physiology, Academic Institute, College of Agriculture, Shizuoka University, Shizuoka, Japan.
Keiichiro
K
Yogo
D000818:Animals; D001483:Base Sequence; D064113:CRISPR-Cas Systems / Q000235:genetics; D004822:Epididymis / Q000378:metabolism / Q000473:pathology; D005260:Female; D005306:Fertilization; D005407:Flagella / Q000502:physiology; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D007248:Infertility, Male / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016296:Mutagenesis; D027361:Organic Anion Transporters / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013081:Sperm Motility / Q000502:physiology*; D013094:Spermatozoa / Q000378:metabolism*; D013737:Testis / Q000378:metabolism / Q000473:pathology
D027361:Organic Anion Transporters