Expression of a2 vacuolar ATPase in spermatozoa is associated with semen quality and chemokine-cytokine profiles in infertile men.
BACKGROUND
A number of laboratory tests have been developed to determine properties of spermatozoa quality but few have been adopted into routine clinical use in place of the WHO semen analysis. We investigated whether Atp6v0a2 (a2 isoform of vacuolar ATPase) is associated with abnormal semen quality and changes in chemokine-cytokine profiles in infertile men.


METHODS
Semen samples were collected from 35 healthy donors and 35 infertile men at the Andrology laboratory from August 2011 to June 2012. The levels of Atp6v0a2 mRNA and protein, and its localization in spermatozoa were determined. a2NTD (the N-terminal portion of Atp6v0a2) and secreted chemokine-cytokine profiles in seminal fluid were measured.


RESULTS
Atp6v0a2 protein (P<0.05) and mRNA (P<0.05) in spermatozoa from infertile men were significantly lower than those from fertile men. Fluorescent microscopy revealed that Atp6v0a2 is mainly expressed in the acrosomal region. Infertile men's seminal fluid had significantly lower G-CSF (P<0.01), GM-CSF (P<0.01), MCP-1 (P<0.05), MIP-1α (P<0.01) and TGF-β1 (P<0.01) levels when compared to the seminal fluid from fertile men. Seminal fluid a2NTD levels were significantly correlated with G-CSF (P<0.01), GM-CSF (P<0.01), MCP-1 (P<0.05), MIP-1α (P<0.01) and TGF-β1 (P<0.01) which are key molecules during the onset of pregnancy.


CONCLUSIONS
These results suggested that a critical level of Atp6v0a2 is required for the fertile spermatozoa and its decreased level in spermatozoa could be used to predict male infertility. This study provides a possibility that Atp6v0a2 could be potentially used as a diagnostic marker for the evaluation of male infertility.
Department of Microbiology and Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA.
Kuniaki
K
Ota
Mukesh Kumar
MK
Jaiswal
Sivakumar
S
Ramu
Rajasinjham
R
Jeyendran
Joanne
J
Kwak-Kim
Alice
A
Gilman-Sachs
Kenneth D
KD
Beaman
D016022:Case-Control Studies; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007248:Infertility, Male / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D021381:Protein Transport; D006180:Proton-Translocating ATPases / Q000235:genetics* / Q000378:metabolism; D012661:Semen / Q000737:chemistry*; D055101:Semen Analysis; D013081:Sperm Motility; D013094:Spermatozoa / Q000378:metabolism*
C525845:ATP6V0A2 protein, human; D018925:Chemokines; D016207:Cytokines; D006180:Proton-Translocating ATPases