Concerning influences of micro/nano plastics on female reproductive health: focusing on cellular and molecular pathways from animal models to human studies

Abstract

The female reproductive system can face serious disorders and show reproductive abnormalities under the influence of environmental pollutants. Microplastics (MPs) and nanoplastics (NPs) as emerging pollutants, by affecting different components of this system, may make female fertility a serious challenge. Animal studies have demonstrated that exposure to these substances weakens the function of ovaries and causes a decrease in ovarian reserve capacity. Also, continuous exposure to micro/nano plastics (MNPs) leads to increased levels of reactive oxygen species, induction of oxidative stress, inflammatory responses, apoptosis of granulosa cells, and reduction of the number of ovarian follicles. Furthermore, by interfering with the hypothalamic-pituitary-ovarian axis, these particles disturb the normal levels of ovarian androgens and endocrine balance and delay the growth of gonads. Exposure to MNPs can accelerate carcinogenesis in the female reproductive system in humans and animal models. Animal studies have determined that these particles can accumulate in the placenta, causing metabolic changes, disrupting the development of the fetus, and endangering the health of future generations. In humans, the presence of micro/nanoplastics in placenta tissue, infant feces, and breast milk has been reported. These particles can directly affect the health of the mother and fetus, increasing the risk of premature birth and other pregnancy complications. This review aims to outline the hazardous effects of micro/nano plastics on female reproductive health and fetal growth and discuss the results of animal experiments and human research focusing on cellular and molecular pathways.

Keywords: Environmental pollutants; Female fertility; Microplastics; Nanoplastics; Reproductive system.

Fig. 1

The effects of micro/nano plastics against the female reproductive system. Accumulation of MNPs in the tissue of the uterus and ovaries leads to oxidative stress, inflammation, and apoptosis in the cells of these tissues, and by weakening the function of these organs, it disrupts their efficiency. In uterine tissue, the reduction of implantation rate can be one of the serious consequences of exposure to MNPs. These plastic particles may also cause ovarian tissue epithelial cells to become cancerous

Fig. 2

Molecular pathways involved in the increase of fibrosis in the ovary and uterus by exposure to micro/nano plastics. The occurrence of fibrosis in the ovary and uterus can be caused by the accumulation of MNPs in these tissues. By increasing the expression of HMGB1, MNPs cause the activation of NOX2 after activating the TLR4 receptor, which ultimately increases the expression of Notch ligands by increasing the level of ROS and ultimately leads to the activation of the Notch signaling pathway. Through cross-talk with the TGF-β signaling pathway and the effective transfer of p-SMAD2/3 to the nucleus, this pathway activates the expression of collagen, α-SMA, MMP2/9, and Hes family, increasing the collagen fibers in the ECM. Also, the activation of the Wnt/β-catenin signaling pathway as a result of exposure to MNPs, with the effective transfer of β-catenin to the nucleus, increases the expression of TGF-β, followed by the increase of collagen in the ECM of the cell which eventually causes fibrosis in the uterus and ovaries

Fig. 3

Schematic representation of the impact of micro/nano plastics on the fetus, offspring, and its various organs. Maternal exposure to MNPs causes the accumulation of these particles in placenta tissue, but among them, only NPs can pass through the BPB and affect different fetal organs. These particles disrupt the fetal immune system and show their negative effects on this organ by increasing inflammation and oxidative stress as well as reducing liver absolute weight. MNPs particles have disturbed the growth and development of the heart and the brain, it leads to a decrease in the expression of genes related to cell division in the hippocampus, and on the other hand, inhibits thalamic GABA synthesis and causes problems in brain development. Also, disturbance in metabolism and reproductive system in both sexes is one of the results of exposure to these harmful particles