Acephate exposure during gestation in rats elicits differing placental transcriptomic responses in male and female fetuses

Acephate, a broadly applied insecticide with endocrine-disrupting properties, has in utero effects that are still not fully elucidated. We hypothesized that maternal exposure to a low dose of acephate alters placental function and induces sex-specific offspring changes. Wistar rat dams received water (control) or acephate (4.5 mg/kg/day) by gavage from gestation day (GD) 6.5-18.5, and the placentas and fetuses were collected on GD 18.5. Acephate exposure caused intrauterine growth restriction (IUGR) in both sexes, while placental efficiency (g fetus/g placenta) was reduced in males and increased in females. Placental transcriptomics revealed no significant differential expression in placentas bearing male fetuses. In contrast, 135 downregulated genes and 171 upregulated genes enriched for growth and nutrient transport were identified in placentas bearing female fetuses. A reduction in the profile of proinflammatory cytokines in the amniotic fluid was detected in the fetuses of both sexes, especially in males, whereas the plasma concentration of MCP-1 increased in dams. Taken together, these findings reveal that the response to acephate differs according to fetal sex, suggesting a nontranscriptional mechanism of placental failure in placentas bearing male fetuses, as well as a complex, adaptive transcriptional response in those bearing female fetuses.