Analysis of spermatogenesis and fertility in adult mice with a hypomorphic mutation in the Mtrr gene

Recent research has focussed on the significance of folate metabolism in male fertility. Knocking down the mouse gene Mtrr impedes the progression of folate and methionine metabolism and results in hyperhomocysteinaemia, dysregulation of DNA methylation and developmental phenotypes (e.g. neural tube, heart and placenta defects). The Mtrr(gt) mouse line is a model of transgenerational epigenetic inheritance (TEI), the hypothesised cause of which is the inheritance of a yet-to-be determined epigenetic factor via the germline. We investigated Mtrr(gt)(/)(gt) testes and sperm function compared with control C57Bl/6J testes to explore potential defects that might confound our understanding of TEI in the Mtrr(gt) model. Histological analysis revealed that adult Mtrr(gt)(/)(gt) testes are more spherical in shape than C57Bl/6J testes, though serum testosterone levels were normal and spermatogenesis progressed in a typical manner. Spermatozoa collected from the cauda epididymis showed normal morphology, counts, and viability in Mtrr(gt)(/)(gt) males. Correspondingly, Mtrr(gt) spermatozoa contributed to normal pregnancy rates. Similar parameters were assessed in Mtrr(+/+) and Mtrr(+/)(gt) males, which were normal compared with controls. Overall, our data showed that the Mtrr(gt) allele is unlikely to alter spermatogenesis or male fertility. Therefore, it is improbable that these factors confound the mechanistic study of TEI in Mtrr(gt) mice.