Introduction: It is becoming clear that epigenetic modifications, such as DNA methylation, exhibit dynamic and reversible changes. Our understanding of a role for epigenetic modifications for timing biological rhythms is in its infancy. It has recently been found that DNA methylation in the hypothalamus plays a role in regulating the internal representation of seasonal timing. Here we tested the hypothesis that epigenetic modifications are also responsible for controlling reproductive rhythms across a number of timescales in peripheral reproductive tissues.
Methods: Using a seasonally breeding animal model, the Siberian hamster (Phodopus sungorus), we examined the naturally occurring seasonal and estrus variation in mRNA expression of DNA methyltransferase (dnmt) and histone deacetylase (hdac) expression in the uterus.
Results and Discussion: SD conditions induced reproductive involution and a significant increase in uterine dnmt3a and hdac2 expression. One-way ANOVA revealed a significant difference in dnmt3a expression across the estrus cycle levels decrease during oestrus. Ovariectomised hamsters treated with a single bolus of estrogen and progesterone were found to have significantly lower uterine dnmt3a expression. Conversely, there was a significant increase in hdac1 and hdac3 during oestrus. These data provide novel and robust evidence that dnmt3a expression is dynamic across a number of different timescales. We propose that variation in DNMT3a is involved in the local timing of reproductive physiology in key tissues. These data have significant implications for our understanding of the potential effects of DNA methylation for fertility in a rodent species with direct applications for human reproductive health. Uncovering the mechanisms that underlie this natural pattern could have a significant impact for developing effective long-term male contraceptives. We suggest that epigenetic modifications are involved in molecular timing across multiple timescales and may represent an evolutionarily ancient clock mechanism. (This work was funded by an SRF Vacation Scholarship and the University of Aberdeen.
11 Jul 2016 - 11 Jul 2016