While plastic is fantastic, the luxury of our synthetic world comes at a price: plasticizing agents can affect our chances of bringing new life into that world thanks to our environmentally-responsive sperm. Phthalates, which are common plasticizing agents, disrupt the endocrine system and are present in food packaging, personal care products such as shaving cream, and even medical equipment.
Inspired by evidence from rodent models demonstrating that phthalates alter the DNA methylation of sperm, the lab of J. Richard Pilsner at the University of Massachusetts Amherst sought to translate this seminal evidence to a human study.
The talented team employed the 450K array to analyze the sperm of the 48 males undergoing in vitro fertilization (IVF) while also examining the concentrations of 17 urinary metabolites related to phthalates and phthalate replacements. Rather than focus on single CpGs, the authors of the study applied the A-clustering algorithm to identify co-regulated CpGs belonging to differentially methylated regions (DMRs).
Here’s what they discovered:
- After adjusting for age, body-mass index, and smoking, 131 DMRs display an association with one or more urinary metabolites
- Sperm DMRs are associated with lincRNAs and coding regions, with the genes having functions related to growth, development, and cell function and maintenance
- Sperm DMRs are relevant to the embryo; 19 DMRs are associated with poor quality blastocyst-stage embryos after IVF
- A separate analysis of imprinted regions, which are critical to development, revealed that the methylation level of 9 regions correlates to a single urinary metabolite
First author Haotian Wu shares, “Rather than looking for methylation changes at individual sites on the DNA, we looked at DNA regions or clusters on genes that might be more biologically meaningful than individual sites. It’s not just numbers we were interested in. We wanted to pay attention not only to the statistical relationships, but also the biology.”
Pilsner concludes, “There has always been this heavy concern in the past with expectant moms not smoking and not drinking, for example, to protect the fetus. In this study, we see that dad’s environmental health contributes to reproductive success. For sperm to mature is a 72-day process, almost three months, and our study shows that this preconception time-period may represent an important developmental window by which environmental exposures may influence sperm epigenetics, and in turn, early life development. So in the same way mom needs to be careful, dad also needs to. It doesn’t surprise me that sperm carry some sort of environmental legacy to the next generation. What the sperm cell encounters during its development can influence these chemical tags or DNA methylated, and it may well have an effect on the developing embryo and offspring.”
Catch all the associations over at Human Reproduction, September 2017