警惕!孕妇铅暴露会影响其孙辈

韦恩州立大学(Wayne State University)的一组研究团队发现孕妇血液中含有高水平铅,不仅会影响尚未出生的胎儿,还会影响其孙子孙女们。该研究在线发表于《Scientific Reports》上,是一项关于几代人的表观遗传学研究:DNA甲基化的改变与母亲暴露在铅有关,能够传递给孙辈。

众所周知,低水平的铅暴露会影响子宫内的胎儿。如果孕妇暴露在铅环境,铅会通过胎盘进入到胎儿发育中的骨和其他器官。孕妇以前暴露过铅也会影响胎儿的大脑,在日后的生活中造成其发育障碍。

由Douglas Ruden博士领导的韦恩州立大学的最新研究,他和研究团队透露铅暴露能造成DNA甲基化的特殊改变,该改变能在第三代的干血斑中检测到。

根据Ruden的说法,在这项研究之前,还未有研究证实第三代产生环境暴露的后生效应。其研究团队验证了(铅暴露孕妇的孙辈)胎儿生殖细胞暴露在环境毒素中,会造成新生血液的表观遗传改变的假说。

“我们的研究结果证实在妊娠过程中铅暴露会影响胎儿生殖细胞的DNA甲基化状态,从而导致孙辈新生儿干血斑DNA甲基化的改变,” Ruden说,“这是第一个证明孕妇环境暴露对孙辈的DNA甲基化模式有后生效应。”

研究团队称这项隔代研究设计或许能鉴别基因,该基因或能成为未来隔代风险评估研究的候选生物学标志。

“我们的初步研究提供间接的证据——孕妇暴露于铅环境中能影响孙辈特定的DNA甲基化的状态。不过,孙辈血液中变化了的DNA甲基化在出生后发育中显然被规范化。另外,暴露于铅的胎儿跟急性暴露的儿童有不同的表观遗传结果。”

A team of researchers at Wayne State University have discovered that mothers with high levels of lead in their blood not only affect the fetal cells of their unborn children, but also their grandchildren. Their study, Multigenerational epigenetic inheritance in humans: DNA methylation changes associated with maternal exposure to lead can be transmitted to the grandchildren, was published online this week inScientific Reports.

It’s a known fact that babies in the womb can be affected by low levels of lead exposure. If a pregnant woman is exposed to lead, the lead passes through the placenta into the baby’s developing bones and other organs. Pregnant women with a past exposure to lead can also affect the unborn child’s brain, causing developmental problems later in life. Previous research studies have suggested that exposure to heavy metal toxicants can influence a person’s global DNA methylation profile.

In the recent Wayne State study led by Douglas Ruden, Ph.D., professor in the Department of Obstetrics & Gynecology and the Institute of Environmental Health Sciences, director of epigenomics, and program leader in the Center for Urban Responses to Environmental Stressors, he and his research team revealed that lead exposure can cause specific changes in DNA methylation, which can be detected in dried blood spots beyond one generation. The neonatal blood spots from both the mothers and children in this study were obtained from the Michigan Neonatal Biobank, a unique resource that has most of the neonatal dried blood spots from children born in Michigan since 1984.

According to Ruden, epigenetic effects of environmental exposures beyond one generation have not yet been demonstrated in humans prior to this study. He and his team tested the hypothesis that human fetal germ cell exposure to environmental toxins causes epigenetic changes in the newborn blood from a grandchild of an exposed pregnant woman.

“Our results suggest that lead exposure during pregnancy affects the DNA methylation status of the fetal germ cells, which leads to altered DNA methylation in grandchildren’s neonatal dried blood spots,” said Ruden. “This is the first demonstration that an environmental exposure in pregnant mothers can have an epigenetic effect on the DNA methylation pattern in the grandchildren.”

The research team stated that this novel, two-generational study design might be able to identify the genes that may serve as possible candidate biomarkers for future transgenerational risk assessment studies.

“Our pilot study provides indirect evidence that lead exposure in women during childbirth can affect the locus-specific DNA methylation status of grandchildren,” said Ruden. “However, the altered DNA methylation profiles of the grandchildren’s blood are apparently normalized during postnatal development. Also, fetal germline exposure to lead apparently has different epigenetic consequences than acute childhood exposure.”