Lactate inhibits germ cell apoptosis in the human testis.
Dysregulation of male germ cell apoptosis has been associated with the pathogenesis of male infertility. Therefore, factors involved in the regulation of germ cell death are being actively investigated. Here, we studied the effects of lactate on human male germ cell death, using as a model a testis tissue culture in which physiological contacts are maintained between the germ cells and the supportive somatic Sertoli cells. Apoptosis of spermatocytes, spermatids and a few spermatogonia was induced by culturing segments of seminiferous tubules under serum-free conditions. This germ cell death was inhibited effectively and dose-dependently by lactate, indicating that it plays a crucial role in controlling cell death cascades of male germ cells. Interestingly, the anti-apoptotic role of lactate was not associated with changes in testicular adenine nucleotide (ATP, ADP and AMP) levels. In the seminiferous tubules, the final site of the death-suppressing action of lactate appeared to be downstream along the cell death pathway activated by the Fas receptor of the germ cells. In conclusion, testicular cell death was effectively regulated by lactate, which may be regarded as a potential compound for optimizing in-vitro methods involving male germ cells for assisted reproduction.
Erkkilä
K
K
Programme for Developmental and Reproductive Biology, Biomedicum Helsinki, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. krista.erkkila@hus.fi
Aito
H
H
Aalto
K
K
Pentikäinen
V
V
Dunkel
L
L
D000225:Adenine / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D046508:Culture Techniques; D006801:Humans; D020287:In Situ Nick-End Labeling; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D010085:Oxidative Phosphorylation; D011471:Prostatic Neoplasms; D012671:Seminiferous Tubules / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D019014:fas Receptor / Q000502:physiology
D019014:fas Receptor; D019344:Lactic Acid; D000225:Adenine