SLC9A3 Protein Is Critical for Acrosomal Formation in Postmeiotic Male Germ Cells

Abstract

Solute carrier family 9 isoform 3 (SLC9A3), a Na+/H+ exchanger, regulates the transepithelial absorption of Na+ and water and is primarily expressed on the apical membranes of the intestinal epithelium, renal proximal tubule, epididymis, and vas deferens. Loss of the Slc9a3 allele in mice enhances intestinal fluid and causes diarrhoea as a consequence of diminished Na+ and HCO3− absorption. Hence, the loss also causes male infertility and reveals the abnormal dilated lumen of the rete testis and calcification in efferent ductules. However, whether loss of Slc9a3 alleles also disrupts mammalian spermatogenesis remains unknown. First, through immunoblotting, we determined that SLC9A3 is highly expressed in the murine testis compared with the small intestine, epididymis, and vas deferens. During murine spermatogenesis, SLC9A3 is specifically expressed in the acrosome region of round, elongating, and elongated spermatids through immunostaining. Furthermore, SLC9A3 signals are enriched in the acrosome of mature sperm isolated from the vas deferens. In Slc9a3 knockout (KO) mice, compared with the same-aged controls, the number of spermatids on the testicular section of the mice progressively worsened in mice aged 20, 35, and 60 days. Sperm isolated from the epididymis of Slc9a3 KO mice revealed severe acrosomal defects. Our data indicated that SLC9A3 has a vital role in acrosomal formation during spermiogenesis.

Deficiency of the Tbc1d21 gene causes male infertility with morphological abnormalities of the sperm mitochondria and flagellum in mice

“…All protocols were used as utilized in our previous study [34]. The sperm were collected from the epididymides and vas deferens from 3-month-old mice and were immediately fixed with 4% paraformaldehyde and 0.1% glutaraldehyde overnight at 4˚C.…”

Down-regulated Solute Carrier Family 4 Member 4 Predicts Poor Progression in Colorectal Cancer

“…Some of these known or predicted interacted genes had been reported to be oncogenes or tumor suppressor genes [23][24][25][26] . For example, SLC9A3 an exchanger of Na + /H + , regulates the transepithelial absorption of Na+ and water and is principally expressed in the apical membranes of the intestinal epithelium, renal proximal tubule, epididymis, and vas deferens [40] . Loss of the SLC9A3 allele may result in diminished Na + and HCO3 − absorption, which suggests that SLC9A3 plays a vital role on the apical membranes of the intestinal epithelium, renal proximal tubule, epididymis, and vas deferens [34].…”

Role of 11β-hydroxysteroid dehydrogenase type 1 in the development of atopic dermatitis

“…The role of 11β-HSD1 in AD has not been studied yet. However, evidence from recent studies supports the notions that 11β-HSD1 is involved in inflammatory cytokine expression in keratinocytes and that it plays an important role in AD exacerbation by modulating local GC availability 14 . The expression of thymic stromal lymphopoietin (TSLP) is significantly increased in the epidermis of keratinocyte-specific Hsd11b1 KO compared to that in WT mice 33 .…”

“…11β-Hydroxysteroid dehydrogenases (11β-HSDs) regulate the peripheral availability of GCs. There are two isoforms of 11β-HSD: 11β-HSD1 converts inactive cortisone into cortisol 14 , 15 , whereas 11β-HSD2 inactivates cortisol to cortisone 16 , 17 . Epidermal keratinocytes, dermal fibroblasts, sebocytes, and sweat gland cells in the skin, and the outer root sheath cells of hair follicles express 11β-HSD1 7 , 18 – 20 , and this expression is increased by ultraviolet (UV) B and UVC but not UVA irradiation 17 , 21 .…”

“…AD is one of the most common inflammatory diseases of the skin. It is characterized by severe pruritus and its multifactorial pathogenesis involves a complex combination of epidermal barrier defects, T helper cell type 2 (Th2)-skewed inflammation, and neuroendocrinal dysregulation 14 , 25 – 28 . The involvement of GCs in inflammatory skin diseases such as AD has been proposed recently.…”