Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF) and are associated with congenital bilateral absence of the vas deferens (CBAVD), which is the major cause of infertility in male patients with CF. However, most Taiwanese patients with CBAVD do not carry major CFTR mutations. Some patients have a single copy deletion of the solute carrier family 9 isoform 3 (SLC9A3) gene. SLC9A3 is a Na+/H+ exchanger, and depleted Slc9a3 in male mice causes infertility due to the abnormal dilated lumen of the rete testis and efferent ductules. Furthermore, SLC9A3 interacts with CFTR in the pancreatic duct and functions as a genetic modifier of CF. However, SLC9A3 function and its relation to CFTR expression in the male reproductive tract in vivo remain elusive. In the present study, we found that CFTR expression was dramatically decreased in the epididymis and vas deferens of Slc9a3 knockout mice. Adult Slc9a3-/- mice showed not only significantly decreased epididymis and vas deferens weight but also increased testis weight. Furthermore, Slc9a3-/- mice developed obstructive azoospermia because of abnormal abundant secretions and calcification in the lumen of the reproductive tract. Ultrastructural analysis of the epithelium in Slc9a3–/–epididymis and vas deferens displayed disorganized and reduced number of stereocilia and numerous secretory apparatuses. Our data revealed that interdependence between SLC9A3 and CFTR is critical for maintaining a precise microenvironment in the epithelial cytoarchitecture of the male reproductive tract. The Slc9a3-deficient mice with impaired male excurrent ducts in this study provide proof for our clinical findings that some Taiwanese of CBAVD carry SLC9A3 deletion but without major CFTR mutations.

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.

When the coronavirus disease 2019 (COVID-19) began to ravage the world in 2019, the World Health Organization became concerned. The epidemic has a high mortality and contagion rate, with severe health and psychological impacts on frontline emergency medical service system practitioners. There are many hospital staff surveys, but few have covered the stress among emergency medical technicians. DASS-21, PSQI, and AUDIT questionnaires were used to evaluate the sources of psychological stress factors of firefighters in Taiwan. Multiple logistic regression was used to analyze the questionnaire content. We conducted questionnaire surveys from May 2022 to July 2022. Our sample comprised 688 participants. The odds ratios of increased depression, anxiety, and stress levels due to reduced family or peer understanding and support were 2.72 (95% CI: 1.50–4.92), p = 0.001; 2.03 (95% CI: 1.11–3.68), p = 0.021; and 3.27 (95% CI: 1.83–5.86), p < 0.001, respectively. The odds ratios of poor sleep quality due to depression, anxiety, and increased stress levels were 5.04 (3.18–7.99), p < 0.001; 2.44 (95% CI: 1.57–3.81), p < 0.001; and 4.34 (95% CI: 2.76–6.82), p-value < 0.001, respectively. During the COVID-19 pandemic, poor sleep quality and a lack of understanding and support from the Taiwan firefighting agency staff, family, or peers resulted in increased depression, anxiety, and stress levels.

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