Transgenerational Effects of Endocrine Disruptors

SAN DIEGO — Gestational exposure to polychlorinated biphenyls (PCBs) may have lifelong and transgenerational effects on body weight, hormones and hypothalamic gene expression, researchers reported at ENDO 2015.

Specifically, they observed that prenatal exposure to low doses of PCBs can change the developing brain in an area involved in metabolism, and some effects are apparent even 2 generations later.

In an animal study, researchers found that hereditary effects included increased body weight, but only in descendants of females and not males exposed to PCBs in the womb.

Study co-author Andrea Gore, PhD, who is a professor at the University of Texas at Austin, said these endocrine-disrupting chemicals (EDCs) affect the developing brain differently in males and females. 

“We did this study because we know that exposure to environmental endocrine-disrupting chemicals are particularly problematic during development because the embryo and infant is highly sensitive to both natural hormones and to chemicals that disrupt them,” said Dr. Gore. 

“Our goal was to determine whether and how prenatal EDC exposures affected the brain of the exposed individual, his/her offspring and even the grandchildren. This is very relevant to humans, as all of us, as well as our parents and grandparents, have been and continue to be exposed to EDCs.”

PCBs are known endocrine disruptors and are present in air, water, soil and many products manufactured before these chemicals were banned in the U.S. in 1979. Brain development and function, and their regulation by hormones, are very similar between rats and humans, according to Dr. Gore, and therefore, the results from this rat model may point to the potential vulnerability of the developing human brain to environmental endocrine disruptors.

She and her colleagues gave a mixture of PCBs to pregnant rats at the beginning of their third trimester, thus directly exposing their offspring to the endocrine disruptors. Doses of PCBs were low to be comparable to that of human exposure. Other pregnant rats received a low dose of estrogen to account for PCB’s estrogenic effects and rats in the control group received a placebo instead of PCBs.

The researchers allowed the first-generation rats born to PCB-exposed and control rats to mature and then bred them (both males and females) through two additional generations to see if the effects of PCBs were heritable.

The researchers found that the first generation of PCB-exposed rats had changes to nine genes in their brains. The nine genes were located in the arcuate nucleus, which is a region involved in reproduction and metabolic function. They observed few changes in the second-generation rodents, other than decreased levels of the hormone progesterone in females.

In the third generation, rats descended from animals exposed to low-dose estrogen had changes to three genes in the arcuate nucleus that are involved in biological rhythms and metabolic function. These changes did not occur in descendants of control rats. Because the third generation had no personal exposure to the estrogen, the researchers concluded that the observed changes occurred through some form of inheritance.

Dr. Gore said the reason why the second generation was less affected than the third generation is unclear, but it may have to do with the timing of the original exposure during development. All three generations of rats descended from PCB-exposed females weighed significantly more than the other rats.

“We found that prenatal exposures to PCBs affected several endocrine and neurobiological endpoints in the exposed individuals and in 2 subsequent generations. In particular, animals that descended from PCB-exposed rats were significantly heavier than control (vehicle-exposed rats). Several nervous system genes in the hypothalamus, including genes involved in energy balance and biological rhythm regulation, were also changed across generations,” Dr. Gore told Endocrinology Advisor.

Reference

1. Gore A et al. Abstract FRI-290. Presented at: The Endocrine Society’s 97th Annual Meeting & Expo (ENDO 2015); March 5-8, 2015; San Diego.