Sperm Biology and Infertility

In Sperm Biology and Infertility, we aim to combine two fields with an emerging third one: 1) Sperm Metabolism, Sperm Mitochondria and Sperm Oxygen Radicals Production, 2) Evolutionary Sperm Biology and Ecology, and 3) the role of Dietary Lipids in Sperm Membrane and Metabolism. We mainly use Drosophila and bedbugs Cimex.

Sperm Metabolism, Sperm Mitochondria and Sperm Oxygen Radicals Production

Currently, sperm of most organisms are assumed to be propelled by oxidative phosphorylation, i.e. by the mitochondria. Insects possess two sperm mitochondria, helically wrapped around and along the tail. In Drosophila, sperm mitochondria have a role in the elongation of sperm but other than that, we don’t know much about what they actually do – oxphos maybe, maybe not. We would like to know and one possibility to start addressing this question is to monitor sperm metabolism in males and females, such as using autofluorescence lifetime imaging.

The exclusive maternal inheritance of mitochondria generates the interesting situation that mitochondria-related sperm traits that benefit the father cannot be inherited to the son. This is a theoretical challenge for models that assume that sperm competition drives evolutionary change. Other researchers see a primary role for glycolysis in sperm metabolism. We are using a number of advanced microscopy methods to try and address this issue of sperm metabolism, such as FLIM or a biophysical method to measure reactive oxygen species (ROS). We choose insects to look into this question – after all, they hold the world record in sperm storage: ant queens of at least two species fertilise eggs with sperm they received 30 years ago. How are the queens doing that without sperm showing age-related damage?

And, by the way: how do sperm metabolise external sources without haploid gene expression?

What role does male age play? And can we separate ROS production rate from ROS accumulation? Yes, we can! Sperm from older males had higher mitochondrial ROS levels and a higher metabolic rate but produced ROS at a lower rate (in contrast to gut tissue).

Another area where we look at the role of mitochondria in sperm function is via their interaction with the nucleus. Such mito-nuclear interactions influence male fertility such that some mitochondrial mutations cause male sterility – but only in some but not in other nuclear backgrounds. In collaboration with Damian Dowling’s lab, Monash University, we address some questions around mito-nuclear mismatches using mitolines – where a certain genotype is combined with either of several mitochondrial haplotypes… And then comes dietary variation shaping mito-nuclear phenotypes.

More to come on sperm biology. For the moment see:

Turnell BR, Reinhardt K. 2020. Metabolic rate and oxygen radical levels increase but radical generation rate decreases with male age in Drosophila melanogaster sperm. Journal of Gerontology A. Link.

Wetzker C, Reinhardt K. 2019. Distinct metabolic profiles in Drosophila sperm and somatic tissues revealed by two-photon NAD(P)H and FAD autofluorescence lifetime imaging. Scientific Reports 9:19534. Link

Reinhardt K, Breunig HG, Uchugonova A, König K. 2015. Sperm metabolism is altered during storage by female insects: evidence from two-photon autofluorescence lifetime measurements in bedbugs. Journal of the Royal Society Interface link (open access)

Ribou A-C, Reinhardt K. 2012. Reduced metabolic rate and oxygen radicals production in stored insect sperm. Proceedings of the Royal Society of London B 279: 2196-2203.

Reinhardt K, Ribou A-C. 2013. Females become infertile as the stored sperm’s oxygen radicals increase. Scientific Reports 3:2888

Evolutionary Sperm Biology and Ecology

THEORY. We introduced our ‘manifesto’ of Sperm Ecology as a novel biological concept to study sperm cells (Reinhardt et al. 2015). In there we present overwhelming evidence that sperm function is altered by the environment and urge evolutionary and ecological research not to neglect environmental effects on sperm. This concerns the male, female and immediate sperm environments, it concerns external and internal fertilizers and terrestrial and aquatic habitats. We believe the large evidence for sperm phenotypic plastictywarrants a re-appraisal of some evolutionary assumptions in sperm competition theory, in parallel with our empirical study showing no heritability of sperm competition ability (Dobler & Reinhardt 2016). Genotype-by-environment interaction effects on sperm function exist but their general adaptive significance (e.g. local adaptation) awaits further research. Among other unresolved issues are whether sperm diversification occurs by natural selection acting on sperm function directly or on the male and female micro-environments that optimise plastic performance of sperm (for which we coined the term ‘sperm niches‘).

We also took a comparative approach to sperm metabolism in the male, examining several species of Drosophila finding that sperm metabolism in the male explains female remating rate.

Turnell BR, Reinhardt K. Sperm metabolic rate predicts female mating frequency across Drosophila species. Soon to come ….

Reinhardt K, Dobler R, Abbott JK. 2015. An Ecology of Sperm. Sperm Diversification by Natural Selection. Annual Reviews of Ecology, Evolution and Systematics in 2016. Link

Dobler R, Reinhardt K. 2016. Heritability, evolvability, phenotypic plasticity and temporal variation in sperm-competition success of Drosophila melanogaster. Journal of evolutionary biology 29: 929-941. link

Otti O, Johnston PR, Horsburgh G, Galindo J, Reinhardt K. 2015. Female transcriptomic response to male genetic and nongenetic ejaculate variation. Behavioral Ecology, link

Lipids in the Sperm Membrane

Sperm naturally are rich in polyunsaturated fatty acids (PUFA). This is odd because PUFA are very susceptible to oxidation and lipoxidation is not quite what sperm need to function. We have recently found that Drosophila when fed plant-based sterols and PUFA produce sperm that emit fewer reactive oxygen species than males fed a yeast-based diet. That’s all so far, we have no idea whether these sterols end up in mitochondria, and of course, we have no really an idea what sperm mitochondria do (see previous point).

A second aspect, related to our project on speciation in bedbugs, is the question how the lipids in the blood of bats and humans end up in the sperm cells. We know that something is going on and we also know it has a relationship to sperm metabolism. Watch this space…

Guo R, Reinhardt K. 2020. Dietary polyunsaturated fatty acids affect volume and metabolism of Drosophila melanogaster sperm. Journal of evolutionary biology 33: 544-550. pdf.