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Men wanting to be dads should be careful
Phthalates (pronounced 'thalates') are man made chemical compounds found in plastics and products such as shaving cream, toys, vinyl flooring, wall covering, detergents, lubricating oils, food packaging, pharmaceuticals, blood bags and tubing, nail polish, hair sprays, aftershave lotions, soaps, shampoos, perfumes and more.
Phthalates are ubiquitous, they are detectable in the urine of nearly 100 percent of the U.S. population aged six years and older according to the Center for Disease Control and Prevention. They are called "plasticizers" and used to soften plastic, while also adding to its transparency, durability, and even "shelf-life". Exposure to phthalates is known to disrupt our hormones and has been seen, in human studies, to change semen quality and lower androgen levels.
"There has always been this concern with expectant moms not smoking and not drinking, to protect the fetus. In this study, we see that dad's environmental health also contributes to reproductive success.
Researchers believe their study is among the first in humans to investigate the influence of phthalate exposure on sperm epigenetics and thus embryo development. DNA methylation is a mechanism of epigenetics. It includes the process by which a chemical tag is stuck onto DNA without changing its gene sequences. However, it is involved in controlling gene expression (which means function). These early results from a large, ongoing study led by Pilsner suggest that phthalate levels in fathers to be can be changed epigenetically to modify sperm DNA and affect a couples' reproductive success and offspring.
The study appears in the current issue of Human Reproduction, a monthly journal of the European Society of Human Reproduction and Embryology published by Oxford Journals.
The findings are gathered from the first 48 of an eventual 250 couples. The work has identified 6,479 regions of interest correlating phthalate metabolite exposure and DNA methylation sites. Wu: "Rather than looking for methylation changes at individual sites on DNA, we looked at DNA regions or clusters on genes" Of the 6,479 regions examined, 131 were associated with at least one phthalate metabolite. Most of the phthalates associated with sperm DNA methylation are known or suspected of being anti-androgenic, meaning they can influence hormones. Wu: "The next step, after identifying associated regions, is to try to determine the possible biological meaning. We then examined the common links between genes, that might be affected in these 131 regions." They found many were related to genes involved in growth, development, cell function and maintenance.
Researchers were also interested to see if these phthalate-associated changes in sperm DNA methylation affect early-life development. They found that some sperm DNA methylation regions were also associated with poor blastocyst stage quality before transfer into the uterus to establish an in-vitro pregnancy, Pilsner adds. These early results represent a small sample, researchers stress. It is unclear, so far, if these methylated changes are inherited and will persist during prenatal and postnatal development. Pilsner has recently received a multi-million dollar grant to replicate and validate his findings.
"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 the chemical tags of DNA methylation and may well have an effect on the developing embryo and offspring."
WHAT IS KNOWN ALREADY
Several phthalate compounds and their metabolites are known endocrine disrupting compounds and are pervasive environmental contaminants. Rodent studies report that prenatal phthalate exposures induce sperm DMRs, but the influence of preconception phthalate exposure on sperm DNA methylation in humans is unknown.
STUDY DESIGN, SIZE, DURATION
An exploratory cross-sectional study with 48 male participants from the Sperm Environmental Epigenetics and Development Study (SEEDS).
PARTICIPANTS/MATERIALS, SETTING, METHODS
The first 48 couples provided a spot urine sample on the same day as semen sample procurement. Sperm DNA methylation was assessed with the HumanMethylation 450 K array. Seventeen urinary phthalate and 1,2-Cyclohexane dicarboxylic acid diisononyl ester (DINCH) metabolite concentrations were measured from spot urine samples. The A-clust algorithm was employed to identify co-regulated regions. DMRs associated with urinary metabolite concentrations were identified via linear models, corrected for false discovery rate (FDR).
MAIN RESULTS AND ROLE OF CHANCE
Adjusting for age, BMI, and current smoking, 131 DMRs were associated with at least one urinary metabolite. Most sperm DMRs were associated with anti-androgenic metabolites, including mono(2-ethylhexyl) phthalate (MEHP, n = 83), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP, n = 16), mono-n-butyl phthalate (MBP, n = 22) and cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl (MCOCH, n = 7). The DMRs were enriched in lincRNAs as well as in regions near coding regions. Functional analyses of DMRs revealed enrichment of genes related to growth and development as well as cellular function and maintenance. Finally, 13% of sperm DMRs were inversely associated with high quality blastocyst-stage embryos after IVF.
Authors of the study: Haotian Wu Molly S. Estill Alexander Shershebnev Alexander Suvorov Stephen A. Krawetz Brian W. Whitcomb Holly Dinnie Tayyab Rahil Cynthia K. Sites J. Richard Pilsner.
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Compared to shaving soap, shaving creams are a new invention introduced in the 1940s, later evolving into today's aerosol can products. Traditional shaving soaps typically contain higher amounts of natural oils and glycerin, a product derived from plants. Shaving creams lather much quicker making a shave faster. However, they are chemically based and use phalates for quicker foaming and stiffer lathers.