mtDNA polymorphism and metabolic inhibition affect sperm performance in conplastic mice
BioScientifica / Society for Reproduction and Fertility
Copyright © 2017 by the Society for Reproduction and Fertility
Reason for embargo
A broad link exists between nucleotide substitutions in the mitochondrial genome (mtDNA) and a range of metabolic pathologies, but the exploration of the effect of specific mtDNA genotypes is on-going. Mitochondrial DNA mutations are of particular relevance for reproductive traits, because they are expected to have profound effects on male specific processes as a result of the strict maternal inheritance of mtDNA. Sperm motility is crucially dependent on ATP in most systems studied. However, the importance of mitochondrial function in the production of the ATP necessary for sperm function remains uncertain. In this study, we test the effect of mtDNA polymorphisms upon mouse sperm performance and bioenergetics by using five conplastic inbred strains that share the same nuclear background while differing in their mitochondrial genomes. We found that, while genetic polymorphisms across distinct mtDNA haplotypes are associated with modification in sperm progressive velocity, this effect is not related to ATP production. Furthermore, there is no association between the number of mtDNA polymorphisms and either (a) the magnitude of sperm performance decrease, or (b) performance response to specific inhibition of the main sperm metabolic pathways. The observed variability between strains may be explained in terms of additive effects of single nucleotide substitutions on mtDNA coding sequences, which have been stabilized through genetic drift in the different laboratory strains. Alternatively, the decreased sperm performance might have arisen from the disruption of the nuclear DNA / mtDNA interactions that have co-evolved during the radiation of Mus musculus subspecies.
This work was supported by a Smart Ideas grant from the Ministry of Business, Innovation and Employment (MBIE), New Zealand Government (NJG, DMT, DKD), grants from the Spanish Ministry of Economy and Competitiveness (CGL2011-26341, and CGL2016-80577-P to ERSR), and from the German Science Foundation grant (ExC 306/2 to MH and SI).
This is the author accepted manuscript. The final version is available from BioScientifica via the DOI in this record.
Published online 4 July 2017