Knockout of MCT1 results in total absence of spermatozoa, sex hormones dysregulation, and morphological alterations in the testicular tissue

• Published in: Cell and tissue research 2019-11, Vol.378 (2), p.333-339
• Main Authors: Bernardino, Raquel L., D’Souza, Warren N., Rato, Luis, Rothstein, Jay L., Dias, Tânia R., Chui, Daniel, Wannberg, Sharon, Alves, Marco G., Oliveira, Pedro F.
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Animals; Biomedical and Life Sciences; Biomedicine; Clonal deletion; Cytology; Estradiol - blood; Fertility - physiology; Germ cells; Hormones; Hormones, Sex; Human Genetics; Lactic acid; Lactic Acid - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular Medicine; Monocarboxylic Acid Transporters - genetics; Monocarboxylic Acid Transporters - physiology; Morphology; Neomycin; Proteomics; Regular Article; Seminiferous Tubules - metabolism; Sertoli cells; Sertoli Cells - cytology; Sertoli Cells - metabolism; Sex hormones; Sperm; Spermatogenesis; Spermatogenesis - physiology; Spermatogonia; Spermatozoa; Spermatozoa - cytology; Spermatozoa - metabolism; Steroid hormones; Symporters - genetics; Symporters - physiology; Testes; Tubules
• ISSN: 0302-766X; 1432-0878
• DOI: 10.1007/s00441-019-03028-4

Lactate is a key metabolite for the normal occurrence of spermatogenesis. In the testis, lactate is produced by the Sertoli cells and transported to germline cells. Monocarboxylate transporters (MCTs) are key players in that process. Among the family of MCTs, MCT1 is at least partly responsible for lactate uptake by the germ cells. We aimed to perform a first assessment of the role of MCT1 in male reproductive potential. Mct1 conditional knockout (cKO) mice were used for morphometric evaluation, testicular morphology, and sperm parameter assessment. Serum steroid hormones levels were also measured. cKO animals showed a decrease in gonadosomatic index, testis weight, and seminiferous tubular diameters. Deletion of MCT1 also causes morphological changes in the organization of the seminiferous tubules and on Sertoli cell morphology. These changes resulted in failure of spermatogenesis with depletion of germ cells and total absence of spermatozoa. MCT1 cKO animals presented also hormonal dysregulation, with a decrease in serum 17β-estradiol levels. In conclusion, MCT1 is pivotal for male reproductive potential. Absence of MCT1 results in maintenance of undifferentiated spermatogonia pool and compromised sperm production.