Epigenetics research that was designed to fall one step short of wonderful

This 2015 Edinburgh rodent study found:

“In utero exposure of rats to the analgesics indomethacin or acetaminophen, both of which target PG [prostaglandin] pathways, alters fetal germ cell number and development in both male and female fetuses. This results in modest but detrimental effects on F1 [children] female, but not F1 male, fertility in adulthood.

Fetal (F1) exposure of rats to either analgesic resulted in an effect in the second generation (F2 grand-daughters) that manifested as reduced ovarian size and markedly reduced follicle number in females but with evidence of increased follicle activation. The impact on F2 fertility (which was not studied) is unclear.

Our analgesic exposure regimen coincided with the period of chromatin/epigenetic remodelling of the (F1) fetal germ cells in both sexes, events which also occur in the human in the first trimester of pregnancy. The analgesic effects on F2 ovaries were transmitted via both paternal and maternal F1 lines.”

The limitations section showed that the rodents’ acetaminophen dosage was equivalent to a human overdose:

“We administered only a single dose of analgesics. The dose of acetaminophen which we used, resulted in blood levels of acetaminophen 2.5- to 8-fold higher than the levels reported in humans after normal therapeutic dosing (~60 mg/kg/day, divided into 4 doses) during pregnancy.”

I’m puzzled that the researchers didn’t take one more step, and design a great study. They knew what the additional effort would be, per statements such as:

“The impact on F2 fertility (which was not studied) is unclear.

The analgesic-induced reduction in fetal ovarian germ cell number was of particular concern, as the lifetime complement of oocytes is formed in utero at/around the time of birth in women and rodents.”

F3 great-grandchildren were needed to demonstrate “the impact on F2 fertility.” Testing of F3 great-grandchildren may have also provided evidence for or against transgenerational epigenetic inheritance, because those subjects’ cells would have had no direct exposure effects from analgesics.

Weren’t the researchers at the MRC Centre for Reproductive Health, The Queen’s Medical Research Institute University of Edinburgh, interested in understanding whether or not a pregnant woman who overdosed during her fetus’ early development on an analgesic available to billions of people, could potentially adversely affect not only her (F0) and her children’s (F1) and grandchildren’s (F2) reproductive health, but also her F3 great-grandchildren?

Weren’t the researchers interested in being a part of a great study, one that may have advanced science, one that may have shown whether or not epigenetic information was transmitted between generations in the absence of continued analgesic exposure?

http://www.nature.com/articles/srep19789 “Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences”

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