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

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Blake, Georgina 
Hall, Jessica 
Petkovic, Grace 


Recent research has focused 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 hyperhomocysteinemia, dysregulation of DNA methylation, and developmental phenotypes (e.g., neural tube, heart, placenta defects). The Mtrrgt mouse line is a model of transgenerational epigenetic inheritance (TEI), the hypothesized cause of which is the inheritance of a yet-to-be determined epigenetic factor via the germline. Here, we investigate Mtrrgt/gt testes and sperm function compared to 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. Sperm collected from the cauda epididymis revealed normal morphology, counts, and viability in Mtrrgt/gt males. Correspondingly, Mtrrgt sperm contributed to normal pregnancy rates. Similar parameters were assessed in Mtrr+/+ and Mtrr+/gt males, which were normal compared to controls. Overall, our data shows 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.



Aging, Animals, Ferredoxin-NADP Reductase, Fertility, Folic Acid, Male, Metabolic Networks and Pathways, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Semen Analysis, Spermatogenesis

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Reproduction, Fertility and Development

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CSIRO Publishing


All rights reserved
Lister Institute of Preventive Medicine
Wellcome Trust (105356/Z/14/Z)
The work was funded by: a Wellcome Trust PhD studentship in Developmental Mechanisms (to G.E.T.B.) and a Lister Research Prize (to E.D.W.).