Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS) and Multidisciplinary Unit for Biomedical Research (UMIB), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313, Porto, Portugal.
Amgen Inc., Thousand Oaks, CA, USA.
Cell Tissue Res. 2019 Nov;378(2):333-339. doi: 10.1007/s00441-019-03028-4. Epub 2019 May 9.
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.
乳酸是精子发生正常发生的关键代谢物。在睾丸中,乳酸由支持细胞产生,并运输到生殖细胞。单羧酸转运蛋白(MCTs)是该过程的关键参与者。在 MCT 家族中,MCT1 至少部分负责生殖细胞对乳酸的摄取。我们旨在首次评估 MCT1 在男性生殖潜能中的作用。使用 Mct1 条件性敲除(cKO)小鼠进行形态计量评估、睾丸形态和精子参数评估。还测量了血清类固醇激素水平。cKO 动物的性腺体指数、睾丸重量和生精小管直径降低。MCT1 的缺失也导致生精小管组织和支持细胞形态的形态变化。这些变化导致精子发生失败,生殖细胞耗竭,精子完全缺失。MCT1 cKO 动物还表现出激素失调,血清 17β-雌二醇水平降低。总之,MCT1 对男性生殖潜能至关重要。缺乏 MCT1 会导致未分化精原细胞池的维持和精子生成受损。