Summary: Paternal exposure to chemicals in plastics can affect the metabolic health of offspring for two generations, a new study reports. Parental exposure to DCHP leads to higher resistance and impaired insulin signaling in both the first and second generations of offspring.
Fathers exposed to chemicals in plastics can affect the metabolic health of their offspring for two generations, a University of California, Riverside, mouse study reports.
Plastics, which are now ubiquitous, contain endocrine disrupting chemicals, or EDCs, that have been linked to increased risk of many chronic diseases; parental exposure to EDCs, for example, has been shown to cause metabolic disorders, including obesity and diabetes, in the offspring.
Most studies have focused on the impact of maternal EDC exposure on the offspring’s health. The current study, published in the journal Environment International, focused on the effects of paternal EDC exposure.
Led by Changcheng Zhou, a professor of biomedical sciences in the School of Medicine, the researchers investigated the impact of paternal exposure to a phthalate called dicyclohexyl phthalate, or DCHP, on the metabolic health of first generation (F1) and second generation (F2) offspring in mice. Phthalates are chemicals used to make plastics more durable.
The researchers found that paternal DCHP exposure for four weeks led to high insulin resistance and impaired insulin signaling in F1 offspring. The same effect, but weaker, was seen in F2 offspring.
“We found paternal exposure to endocrine disrupting phthalates may have intergenerational and transgenerational adverse effects on the metabolic health of their offspring,” Zhou said. “To the best of our knowledge, our study is the first to demonstrate this.”
In the case of paternal exposure in the study, intergenerational effects are changes that occur due to direct exposure to a stressor, such as exposure to DCHP of fathers (F0 generation) and his developing sperm (F1 generation). Transgenerational effects are changes passed down to offspring that are not directly exposed to the stressor (for example, F2 generation).
Zhou’s team focused on sperm, specifically, its small-RNA molecules that are responsible for passing information down generations. The researchers used “PANDORA-seq method,” an innovative method that showed DCHP exposure can lead to small-RNA changes in sperm. These changes are undetected by traditional RNA-sequencing methods, which lack the comprehensive overview of the small-RNA profile that PANDORA-seq provides.
The study used only F1 males to breed with unexposed female mice to generate F2 offspring. The team found that paternal DCHP exposure induced metabolic disorders, such as impaired glucose tolerance, in both male and female F1 offspring, but these disorders were seen only in female F2 offspring. The study did not examine F3 offspring.
“This suggests that paternal DCHP exposure can lead to sex-specific transgenerational effects on the metabolic health of their progenies,” Zhou said. “At this time, we do not know why the disorders are not seen in male F2 offspring.”
Zhou stressed that the impact of exposure to DCHP on human health is not well understood, even though DCHP is widely used in a variety of plastic products and has been detected in food, water, and indoor particulate matter. DCHP has also been found in human urinary and blood samples. Indeed, the U.S. Environmental Protection Agency recently designated DCHP as one of 20 high-priority substances for risk evaluation.
“It’s best to minimize our use of plastic products,” Zhou said. “This can also help reduce plastic pollution, one of our most pressing environmental issues.”
Zhou’s earlier mouse study, published in Environmental Health Perspectives in 2021, showed exposure to DCHP leads to increased plasma cholesterol levels.
About this epigenetics research news
Author: Iqbal Pittalwala
Contact: Iqbal Pittalwala – UCR
Image: The image is in the public domain
Original Research: Open access.
“Paternal phthalate exposure-elicited offspring metabolic disorders are associated with altered sperm small RNAs in mice” by Jingwei Liu et al. Environmental Health
Paternal phthalate exposure-elicited offspring metabolic disorders are associated with altered sperm small RNAs in mice
Exposure to ubiquitous plastic-associated endocrine disrupting chemicals (EDCs) is associated with the increased risk of many chronic diseases. For example, phthalate exposure is associated with cardiometabolic mortality in humans, with societal costs ∼ $39 billion/year or more.
We recently demonstrated that several widely used plastic-associated EDCs increase cardiometabolic disease in appropriate mouse models. In addition to affecting adult health, parental exposure to EDCs has also been shown to cause metabolic disorders, including obesity and diabetes, in the offspring.
While most studies have focused on the impact of maternal EDC exposure on the offspring’s health, little is known about the effects of paternal EDC exposure. In the current study, we investigated the adverse impact of paternal exposure to a ubiquitous but understudied phthalate, dicyclohexyl Phthalate (DCHP) on the metabolic health of F1 and F2 offspring in mice.
Paternal DCHP exposure led to exacerbated insulin resistance and impaired insulin signaling in F1 offspring without affecting diet-induced obesity. We previously showed that sperm small non-coding RNAs including tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs) contribute to the intergenerational transmission of paternally acquired metabolic disorders.
Using a novel PANDORA-seq, we revealed that DCHP exposure can lead to sperm tsRNA/rsRNA landscape changes that are undetected by traditional RNA-seq, which may contribute to DCHP-elicited adverse effects.
Lastly, we found that paternal DCHP can also cause sex-specific transgenerational adverse effects in F2 offspring and elicited glucose intolerance in female F2 descendants.
Our results suggest that exposure to endocrine disrupting phthalates may have inter- and transgenerational adverse effects on the metabolic health of their offspring.
These findings may increase our understanding of the etiology of chronic human diseases originating from chemical-elicited intergenerational and transgenerational effects.