Analysis of spermatogenesis and fertility in adult mice with a hypomorphic mutation in the Mtrr gene
Georgina E. T. Blake A B , Jessica Hall A , Grace E. Petkovic A and Erica D. Watson
A B C
+ Author Affiliations
- Author Affiliations
A Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, UK.
B Centre for Trophoblast Research, University of Cambridge, Cambridge, CB2 3EG, UK.
C Corresponding author. Email: edw23@cam.ac.uk
Reproduction, Fertility and Development 31(11) 1730-1741 https://doi.org/10.1071/RD19064
Submitted: 20 February 2019 Accepted: 16 June 2019 Published: 20 September 2019
Abstract
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 Mtrrgt 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 Mtrrgt/gt testes and sperm function compared with control C57Bl/6J testes to explore potential defects that might confound our understanding of TEI in the Mtrrgt model. Histological analysis revealed that adult Mtrrgt/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 Mtrrgt/gt males. Correspondingly, Mtrrgt 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 Mtrrgt allele is unlikely to alter spermatogenesis or male fertility. Therefore, it is improbable that these factors confound the mechanistic study of TEI in Mtrrgt mice.
Additional keywords: folate metabolism, folic acid, one-carbon metabolism, testes
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