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Exposure of the fetus to hormone disruptors alters fertility for generations

Exposure of the fetus to hormone disruptors alters fertility for generations

These hormonal pollutants alter genes involved in testicular development and male fertility for generations after the first exposure during fetal life.

The work has been developed with mice exposed during the embryonic period, maternal route, to the vinclozolin, a widely used fungicide in agriculture that has antiandrogen effects (which inhibit male sex hormones), as Jesús del Mazo, a CSIC researcher at the Center for Biological Research explains: “The study shows that the effects may be due to the deregulation of small RNAs, which in turn regulate the expression of coding genes in key proteins in the formation of germ cells ”, adds Del Mazo, who has led the study in collaboration with groups from the French CNRS and the Czech Academy of Sciences.

Both male fertility, as well as the expression of RNAs and the genes they regulate, are altered in the same way during three generations of males, after exposure only in the first generation. And with doses lower than the levels in which they were indicated as "no observed adverse effects", according to the NOAEL toxicity index, explains Del Mazo. This index indicates that below the level of 12 milligrams per kilo of weight per day, no adverse effects have been observed.

The study has been done with a level of 1 milligram per kilo of weight per day, where the aforementioned adverse effects have been observed.

Adverse environmental circumstances during the development and life of organisms are capable of modifying gene expression without altering the base sequences in DNA. These so-called “epigenetic” modifications are responsible for the appearance of multiple pathologies such as some cases of cancer or infertility.

"Some of these epigenetic alterations and their consequences can be transmitted over several generations, as demonstrated in this study"

Although in most of them they are due to changes in dynamic DNA processes, such as their levels of methylation (the main epigenetic mechanism), in this case small RNA molecules are the cause of such transgenerational epigenetic alterations, transmitted via the father without modifications in DNA methylation, explains Del Mazo.

These new RNA-mediated epigenetic mechanisms, which have also recently been demonstrated in the C. elegans worm, may provide new elements to consider at the origin of many diseases and expand the notion of “transgenerational memory of past diseases”, especially those that occurred during fetal life.

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Video: Exposure to Phthalates and Aging (July 2021).