Silent Invaders: the emerging impact of micro-, nanoplastics and plasticizers on human placental development and pregnancy outcomes

• Plastics threaten the placenta through both particulate exposure and chemical additives. • Plastic-derived particles and chemicals induce placental cell death via oxidative stress. • Plastic pollutants impair placental development, leading to fetal growth restriction. • Plastic additives such as bisphenols disrupt endocrine pathways essential for pregnancy. • Research must address mixtures with human-relevant models. The placenta is a multifunctional organ essential for fetal growth, immune tolerance, and endocrine regulation. Increasing evidence indicates that micro- and nanoplastics (MNPs), and their chemical additives like bisphenols and phthalates can cross biological interfaces, accumulate in placental tissues, and impair their structure and function. Given the central role of the placenta in pregnancy maintenance, these findings raise concern regarding the potential consequences of ubiquitous plastic pollution for reproductive health. This manuscript first provides a brief overview of placental architecture, and physiological roles, followed by a summary of the physicochemical characteristics of plastics, major routes of human exposure, and mechanisms of systemic transport and translocation to the placenta. The core of the review focuses on experimental evidence from in vitro and in vivo models describing how MNPs and chemicals are internalized by placental cells, alter cellular homeostasis, and impair vascular, metabolic, endocrine, and immune functions. Particular attention is given to size- and surface chemistry–dependent uptake, oxidative stress, inflammation, hormonal disruption, and epigenetic alterations. Finally, we identify key research gaps and outline future directions, including the need for environmentally relevant exposure models, studies on combined contaminant effects, biomarker development, and regulatory actions to reduce exposure. Through this synthesis, we aim to clarify current understanding of how pervasive plastic pollutants may threaten placental health and, ultimately, maternal and fetal well-being. Graphical Abstract: Placental toxicity mechanisms induced by micro(nano)plastics and plasticizers. Schematic summary of cellular and molecular alterations observed in in vitro and in vivo models following exposure to micro(nano)plastics (MNPs) and plastic-associated chemicals. Key pathways include oxidative stress, inflammation, membrane disruption, and apoptosis, contributing to placental dysfunction.