Sunday, July 24, 2005

Legacy without end

Recently, a research article in Science caught my eye: “Epigenetic Transgenerational Actions of Endocrine Disruptors and Male Fertility”1 and it is a stunner. The key word is “transgenerational,” because the damage described has been documented to the fourth generation of offspring, so far.

Just a single dose of a fungicide (or most probably, any of numerous other ubiquitous endocrine disruptors) to a pregnant rat was found to produce huge deficits in the fertility of males that were effectively the great-great-grandsons of the dosed female, as measured in the offspring of those males still able to produce offspring; many were completely infertile along the way.

Endocrine disruptors have been widely reported to adversely affect male fertility in mammals and other vertebrates, but this is the first paper to document that such germ line damage is then passed to subsequent generations, for at least four generations. Other research2 determined that the same “epigenetic” mode of inheritance also produced demonstrable changes, such as coat color, in subsequent generations.

Researchers have also noted that exposure to pesticides (many of which are endocrine disruptors) causes both reduced quantity and viability of sperm in humans3, primarily in rural areas where pesticide exposures tend to be higher, and that these deficits are directly correlated with the quantity of pesticides measured in the men.

If we needed any more cause for concern over these chemicals (not just pesticides, but also PCBs, PBDEs, bisphenol A, phthalates, and others), such compounds also have been found to cause cognitive effects4 analogous to attention deficit hyperactivity disorder (ADHD). Are such cognitive effects also transgenerational in nature?

This is a wake-up call, about the potential for lasting change to the genome that does not come from genetic mutation, but from epigenetic alterations. Unlike a chromosomal mutation that would randomly change the genetic code, producing different varieties of mutations, epigenetic changes address the state of chemical modification of DNA, which alters the rate at which the genes coded by that DNA are expressed.

Methylation (the addition of -CH3 groups to DNA) is one such epigenetic mechanism that has been widely studied, and it is also the type of epigenetic change addressed in the studies cited here. With epigenetic change having been shown to produce heritable changes, we need to entirely rethink the sorts of assays we do to assess whether a given substance is a mutagen, because substances that are not mutagens may produce epigenetic changes that are every bit as significant as any mutational change.

The terse concluding line of the abstract1 is an understatement of vast proportions:

“The ability of an environmental factor…to reprogram the germ line and to promote a transgenerational disease state has significant implications for evolutionary biology and disease etiology.”

“To reprogram the germ line”: that’s what it’s all about. Blunderingly, we are presently “reprogramming the germ line” of potentially every mammalian species on earth, including our own. This is the legacy we leave to future generations? Not only have we polluted every corner of the planet, but we’ve also polluted our own genome? And faced with that horrid realization, will we try to reverse course?

At least the extinction of the dinosaurs, tragic as it was for the dinosaurs, was not something of their own deliberate creation. It does appear that we humans are endowed with far more brains than common sense, and too much ability to do lasting harm without any concomitant understanding of what it is we’re doing. Perhaps anthropogenic germ line modification will take care of all that for us. What a pathetic waste.

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1“Epigenetic Transgenerational Actions of Endocrine Disruptors and Male Fertility,” Matthew D. Anway, Andrea S. Cupp, Mehmet Uzumcu, and Michael K. Skinner. Science, June 3, 2005.

2“Transgenerational inheritance of epigenetic states at the murine AxinFu allele occurs after maternal and paternal transmission,” Vardhman K. Rakyan, Suyinn Chong, Marnie E. Champ, Peter C. Cuthbert, Hugh D. Morgan, Keith V. K. Luu, and Emma Whitelaw. Proceedings of the National Academy of Sciences, March 4, 2003.

3“Semen Quality in Relation to Biomarkers of Pesticide Exposure,” Shanna H. Swan, Robin L. Kruse, Fan Liu, Dana B. Barr, Erma Z. Drobnis, J. Bruce Redmon, Christina Wang, Charlene Brazil, James W. Overstreet, and the Study for Future Families Research Group. Environmental Health Perspectives, September 2003.

4“Cognitive Effects of Endocrine-Disrupting Chemicals in Animals,”
Susan L. Schantz and John J. Widholm. Environmental Health Perspectives, December 2001.


A sampling of related article links:

“Pesticides reduce fertility in males and their offspring,” Rowan Hooper. NewScientist, June 11, 2005.

“Endocrine Disrupters Trigger Fertility Problems in Multiple Generations,” Jocelyn Kaiser. Science, June 3, 2005.

A list of related articles, with synopses, by ProtectingOurHealth.org

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