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Table 2 Key animal studies informing Heartland Study hypotheses

From: Perinatal health effects of herbicides exposures in the United States: the Heartland Study, a Midwestern birth cohort study

Perinatal exposure to a glyphosate-based herbicide impairs female reproductive outcomes and induces second-generation adverse effects in Wistar rats

(Milesi et al., 2021)

Glyphosate

Increased resorptions in rats

Perinatal exposure to low doses of a GBH impaired female reproductive performance and induced fetal growth retardation and structural congenital anomalies in F2 offspring

Epigenetic disruption of estrogen receptor alpha is induced by a glyphosate-based herbicide in the preimplantation uterus of rats

(Rossetti et al., 2021) (Lorenz et al., 2019)

Glyphosate

Epigenetic changes in rodents

Perinatal exposure to a GBH causes long-term epigenetic disruption of the uterine estrogen-receptor α gene, which could be associated with the GBH-induced implantation failures

Maternal glyphosate exposure causes autism-like behaviors in offspring through increased expression of soluble epoxide hydrolase (sEH)

(Pu et al., 2020)

Glyphosate

Autism-like traits in mice

The glyphosate exposures used here exceed any reasonable dietary, environmental, or occupational exposure, but they indicate that increased sEH plays a role in ASD-like behaviors in offspring

Assessment of Glyphosate Induced Epigenetic Transgenerational Inheritance of Pathologies and Sperm Epimutations: Generational Toxicology

(Kubsad et al., 2019)

Glyphosate

Epigentic changes in rats

Support for an association between glyphosate exposure and transgenerational germline epimutations

Reproductive toxicity of Roundup herbicide exposure in male albino rats

(Owagboriaye et al., 2017)

Glyphosate

Decreased sperm count and motility, increased abnormal sperm morphology

The lowest sperm count was observed in rats exposed to Roundup at 248.4 mg/kg bodyweight of glyphosate

Effects of neonatal exposure to a glyphosate-based herbicide on female rat reproduction

(Ingaramo et al., 2016)

Glyphosate

Increased resorption sites in rats

Alterations in endometrial decidualization might be the mechanism of GBH-induced post-implantation embryo loss

Pre- and postnatal exposure to low dose glufosinate ammonium induces autism-like phenotypes in mice

(Laugeray et al., 2014)

Glufosinate

Autism phenotypes in mice

A neurobehavioral test battery revealed significant effects of GLA maternal exposure on early reflex development, pup communication, affiliative behaviors, and preference for social olfactory cues, but emotional reactivity and emotional memory remained unaltered. These behavioral alterations showed a striking resemblance to changes seen in animal models of Autistic Spectrum Disorders

  1. Legend: CI Confidence Interval, HR Hazard Ratio, OR Odds Ratio, aOR Adjusted Odds Ratio, β Beta Coefficient r = Spearman’s rank-based correlation