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The sodium/proton exchanger SLC9C1 ( sNHE ) is essential for human sperm motility and fertility
Author(s) -
Cavarocchi Emma,
Whitfield Marjorie,
Chargui Ahmed,
Stouvenel Laurence,
Lorès Patrick,
Coutton Charles,
Arnoult Christophe,
Santulli Pietro,
Patrat Catherine,
ThierryMieg Nicolas,
Ray Pierre F.,
Dulioust Emmanuel,
Touré Aminata
Publication year - 2021
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13927
Subject(s) - asthenozoospermia , sperm motility , biology , sperm , capacitation , microbiology and biotechnology , male infertility , genetics , infertility , pregnancy
Abstract Asthenozoospermia, defined by the absence or reduction of sperm motility, constitutes the most frequent cause of human male infertility. This pathological condition is caused by morphological and/or functional defects of the sperm flagellum, which preclude proper sperm progression. While in the last decade many causal genes were identified for asthenozoospermia associated with severe sperm flagellar defects, the causes of purely functional asthenozoospermia are still poorly defined. We describe here the case of an infertile man, displaying asthenozoospermia without major morphological flagellar anomalies and carrying a homozygous splicing mutation in SLC9C1 ( sNHE ), which we identified by whole‐exome sequencing. SLC9C1 encodes a sperm‐specific sodium/proton exchanger, which in mouse regulates pH homeostasis and interacts with the soluble adenylyl cyclase (sAC), a key regulator of the signalling pathways involved in sperm motility and capacitation. We demonstrate by means of RT‐PCR, immunodetection and immunofluorescence assays on patient's semen samples that the homozygous splicing mutation ( c.2748 + 2 T > C ) leads to in‐frame exon skipping resulting in a deletion in the cyclic nucleotide‐binding domain of the protein. Our work shows that in human, similar to mouse, SLC9C1 is required for sperm motility. Overall, we establish a homozygous truncating mutation in SLC9C1 as a novel cause of human asthenozoospermia and infertility.