Glyphosate and a glyphosate-based herbicide induce fetal growth retardation in second-generation rat offspring

CADAVIZ DB; PACINI G; VARAYOUD J; LORENZ V; MILESI MM

Modalidad virtual

Simposio; International Symposium on Reproductive Health; 2021

Epidemiological evidence indicates that maternal exposure to pesticides is associated with stillbirth, altered birth weight or congenital defects. Glyphosate-based herbicides (GBHs) are the pesticides most applied worldwide, and the effects of commercial formulations and its active ingredient glyphosate (Gly) on reproductive health of present and future generations constitute a matter of global interest. We aimed to evaluate whether in utero and lactational exposure to Gly or a GBH induce growth alterations or congenital anomalies in second-generation (F2) offspring.Gly or a GBH (2 mg of glyphosate/kg/day) was administered to F0 pregnant rats through food from gestational day (GD) 9 until weaning. The serum levels of Gly were determined in F0 dams on GD22 and lactational day 21 by UHPLC-MS/MS. Sexually mature F1 females became pregnant and on GD19, F2 fetuses were removed. Morphometric features of F2 offspring were examined: fetal weight, length and morphology, placental weight and placental index. Glyphosate serum levels in F0 dams were similar along the treatment, however, higher levels of Gly were detected in GBH-exposed dams (p < 0.05). F2 fetuses from Gly and GBH-exposed groups exhibited decreased fetal weight and length. Higher occurrence of small for gestational age (SGA) F2 fetuses was observed in GBH (57.5%) and Gly (45.4%) groups in comparison to controls (22%), denoting a delayed growth. The relative risk of being SGA was 2.62 [95% CI (1.70, 4.02); p < 0.001] for GBH F2 fetuses and 2.06 [95% CI (1.33, 3.20); p < 0.001] for Gly F2 fetuses. Although no changes in placental weight were detected, an increase in placental index was observed in Gly group. No structural congenital anomalies were observed. Both Gly and GBH induced multigenerational effects evidenced by fetal growth retardation. Differences between GBH and Gly effects could indicate particular mechanisms of action of the commercial formulation and active ingredient.