Perinatal exposure to 4-nonylphenol affects adipogenesis in first and second generation rats offspring

• Perinatal exposure to 4-NP alters adipogenesis in the next two generations.
• ERα signaling pathway was involved in the 4-NP's effect.

Maternal exposure to 4-nonylphenol (4-NP) during pregnancy was shown to alter adipogenesis in rodents, yet whether the effects are restricted to 4-NP-exposed offspring only or can be transmitted to the next generation are not known. Pregnant Wistar rats received either vehicle or 4-NP (5, 25 and 125 μg/kg/day) from gestation to postnatal day 21. F1 pups were subjected to blood biochemistry tests, or killed to obtain their gonadal fat to determine gene expression. Some F1 adult female rats were mated with F1 males from control group to obtain F2 pups, but without any exposure to 4-NP in the perinatal stage. F2 pups underwent studies similar to those performed on F1 pups. Serum total cholesterol, leptin levels were significantly elevated, the quantity and size of fat cells were increased, gene expression of key regulators of adipogenesis and lipogenic pathway of fat tissue were perturbed by 4-NP (p < 0.05 or p < 0.01). In addition, the expression of mRNA levels and protein of ERα were downregulated in adipose tissue in the two generation offspring. Perinatal exposure to 4-NP affects the adipogenesis in both male and female F1 offspring, and this effect can be progressed to the F2 offspring through the maternal line.