Maternal exposure to phthalates and nanoplastics, isolated or combined: Impacts on placental structure, development, and antioxidant defense as a trigger for maternal-fetal adversities.

The placenta is an essential maternal-fetal organ for the healthy development of the fetus, linking maternal and fetal circulations. Endocrine disrupting chemicals (EDCs), such as phthalates derived from plastic residues, may impair offspring development and increase the risk of metabolic disorders. Plastics also degrade into microplastics (MPs) and nanoplastics (NPs), which can cross the placenta, carrying EDCs and impacting fetal development. The objective of this study was to investigate whether gestational exposure to a phthalate mixture (PM) and NPs interferes with the maternal-fetal interface, altering female reproductive efficiency and placental morphophysiology. Pregnant SD rats were divided into 6 groups: CTR(control; vehicle), T1(20 μg/kg/day-PM), T2(200 mg/kg/day-PM), T3(1 mg/kg/day NPs-100nm), T4(20 μg/kg/dayPM+1 mg/kg/day-NPs-100nm), and T5(200 mg/kg/day-PM+1 mg/kg/day-NPs-100 nm). Treatment was administered orally from gestational day 5 (GD5) to GD20. At GD20, 5-8 rats from each group were anesthetized and underwent laparotomy, and blood, ovaries, uterus, and placentas were analyzed. There was an increase in pre-implantation loss in T3, T4 and T5 groups, a reduction in placental weight, and an increase in placental efficiency in male offspring in T3 group. An increase in the number of fetuses small for gestational age was observed in T3 and T5 vs. C. Furthermore, the treatment caused an increase in the expression of targets related to trophoblast cell differentiation in T5, and growth factors related to angiogenesis in the placenta in T3 and T4 groups. There was a decrease in TBARS, SOD, and GSTpi levels in T2, while CAT increased in T3, suggesting that these pollutants modulate placental gene expression and energy metabolism.