Endurance training remodels sperm-borne small RNA expression and methylation at neurological gene hotspots

Abstract

Remodeling of the sperm epigenome by lifestyle factors before conception could account for altered metabolism in the next generation offspring. Here, we hypothesized that endurance training changes the epigenome of human spermatozoa. Using small RNA (sRNA) sequencing and reduced representation bisulfite sequencing (RRBS), we, respectively, investigated sRNA expression and DNA methylation in pure fractions of motile spermatozoa collected from young healthy individuals before, after 6 weeks of endurance training and after 3 months without exercise. Expression of 8 PIWI interacting RNA were changed by exercise training. RRBS analysis revealed 330 differentially methylated regions (DMRs) after training and 303 DMRs after the detraining period, which were, in both conditions, enriched at close vicinity of transcription start sites. Ontology analysis of genes located at proximity of DMRs returned terms related to neurological function at the trained state and, to a much lesser extent, at the detrained state. Our study reveal that short-term endurance training induces marked remodeling of the sperm epigenome, and identify genes related to the development of the central nervous system as potential hot spots for epigenetic variation upon environmental stress.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0446-7) contains supplementary material, which is available to authorized users.

Sperm RNA code programmes the metabolic health of offspring

“…For example, the sperm RNA signature could be used as a clinical marker of offspring metabolic disease susceptibility. In addition, as human sperm RNA profiles are known to be efficiently altered by improved body condition 1,[83][84][85] , the signature could be monitored before a planned pregnancy and clinical guidance (such as improvements to lifestyle) could also be introduced if necessary to reshape the sperm RNA code towards a healthy condition (Fig. 3).…”

The contribution of epididymosomes to the sperm small RNA profile

“…Collectively, from the studies summarised in Table 1, it is now apparent that an array of paternal stressors, ranging from dietary perturbation (e.g. high fat, low protein), chronic psychological stress, ethanol consumption, environmental pollution and cigarette smoke exposure, can each differentially alter the sRNA profile of sperm of exposed males , Marczylo et al 2012, Rodgers et al 2013, Saavedra-Rodriguez & Feig 2013, Gapp et al 2014, Metzler-Guillemain et al 2015, Paris et al 2015, de Castro Barbosa et al 2016, Donkin et al 2016, Fullston et al 2016, Murashov et al 2016, Rompala et al 2016, Sharma et al 2016, Short et al 2016, Benito et al 2018, Dickson et al 2018, Ingerslev et al 2018, Rompala et al 2018. Further, some of these studies went on to demonstrate that an altered sperm sRNA profile contributed to altered phenotypic outcomes in the offspring post fertilisation.…”

Sperm Epigenetics and Its Impact on Male Fertility, Pregnancy Loss, and Somatic Health of Future Offsprings

“…Several other studies have demonstrated that nutritional status, physical activity levels, endocrine disruptors, and stress can alter sperm epigenetics. [62][63][64] The implications of these findings are intriguing as we are not only learning that environmental factors can alter epigenetic programming, but we are also discovering that this epigenetic reprogramming can be transmitted to offspring. This begs the question about the impact of common vices of men on sperm epigenetic reprogramming and potential transmission to offsprings.…”