TABLE 2.

Principal characteristics and functions of SLC26A3, A6, A8, and CFTR in the sperm and epididymal cells.

Protein	Expression in male reproductive organs	Protein location in sperm	Protein location in epididymis	Mouse KO phenotype in sperm	Mouse KO phenotype in epididymis	Mutations and associated diseases in Humans	References
SLC26A3 (DRA/CLD)	Human: testis (male germ cells), efferent ducts (non-ciliated cells) and ductus epididymis (apical mitochondrial rich cells. Mouse: spermatozoa	Flagellum: midpiece	Luminal border of apical mitochondrial rich cells	Homozygous Slc26a3-null mice: Oligo-astheno-terato-zoospermia, Sperm capacitation defects	Homozygous Slc26a3 knock-out mice: Epididymal dysplasia and granulome in the cauda	Homozygous loss of function: Congenital Chloride Diarrhea (CLD) with male subfertility (oligo-astheno-zoospermia) Heterozygous loss of function: Male infertility (asthenozoospermia)	Hihnala et al., 2006; Hoglund et al., 2006; Chavez et al., 2012; Wedenoja et al., 2017; El Khouri et al., 2018
SLC26A6 (CFEX/PAT1)	Human: efferent ducts (non-ciliated cells), ductus epididymis (apical mitochondrial rich cells). Mouse: spermatozoa	Flagellum: midpiece	Apical mitochondrial rich cells	Homozygous Slc26a6-null mice: No sperm phenotype	Homozygous Slc26a6 knock-out mice: No epididymal phenotype	Not reported	Kujala et al., 2007; El Khouri et al., 2018
SLC26A8 (TAT1)	Human and mouse: testis (male germ cells), spermatozoa.	Flagellum : annulus Equatorial segment	Head: Not expressed	Homozygous Slc26a8-null mice: Asthenozoospermia Sperm capacitation defects	Homozygous Slc26a8 knock-out mice: No epididymal phenotype	Heterozygous loss of function: Male infertility (asthenozoospermia)	Toure et al., 2001; Lohi et al., 2002; Kujala et al., 2007; Hildebrand et al., 2010; Rode et al., 2012; Dirami et al., 2013
CFTR	Human: efferent ducts (non-ciliated cells), ductus epididymis (apical mitochondrial rich cells), vas deferens spermatozoa. Mouse: spermatozoa	Flagellum: midpiece. Equatorial segment	Head: Luminal border of apical mitochondrial rich cells	Heterozygous CFTR tm1Unc: reduced sperm capacitation and fertilization potential	Homozygous DeltaF508 (DeltaF/DeltaF) and knock-out (cf/cf) CFTR mice: normal epididymis but collased lumen of the vas deferens	Homozygous loss of function: Cystic fibrosis (CF); Isolated obstructive azoospermia in non-CF patients : congenital bilateral absence of the vas deferens, (CBAVD)	Tizzano et al., 1994; Reynaert et al., 2000; Patrizio and Salameh, 1998; Claustres, 2005; Hernández-González et al., 2007; Touré et al., 2007; Xu et al., 2007 (Book chapter: https://doi.org/10.1159/000477279)

The table summarizes the tissues within the male reproductive organs where SLC26A3, A6, A8, and CFTR genes are expressed and the detection of the corresponding proteins in sperm and epididymal cells. The sperm and epididymal phenotypes in the mouse knock out mouse models are reported together with the phenotype associated with mutations in those genes in humans. References for information summarized in the table are indicated.