Multigenerational effects of perinatal glyphosate exposure in rats: Developmental alterations, increased mortality and oxidative imbalance.

Glyphosate (Gly), the active ingredient in glyphosate-based herbicides (GBHs), is the most widely used agrochemical, raising concerns about developmental toxicity. This study evaluated the multigenerational effects of perinatal GBH or Gly exposure on fetal and postnatal development. Pregnant Wistar rats received vehicle, GBH, or Gly (2 mg Gly/kg/day) orally from gestational day 9 until weaning. Adult F1 females were mated to generate F2 offspring. In F1 and F2 generations, fetal growth and intrauterine oxidative stress markers were assessed, and postnatal growth and survival were monitored. Glyphosate was detected in amniotic fluid, confirming transplacental transfer. GBH and Gly altered intrauterine antioxidant enzyme activities and lipid peroxidation levels across generations and F2 fetuses exhibited intrauterine growth restriction. Postnatally, male offspring showed increased vulnerability evidenced by reduced body weight and increased mortality, particularly in F2. These findings demonstrate GBH/Gly exposure induce developmental toxicity with more severe and sex-specific effects in the second generation.