Abstract
Fine particulate matter (PM) has a small diameter but a large surface area; thus, it may have broad toxic effects that subsequently damage many tissues of the human body. Interestingly, many studies have suggested that the recent decline in female fertility could be associated with increased PM exposure. However, the precise mechanisms underlying the negative effects of PM exposure on female fertility are still a matter of debate. A previous study demonstrated that resident stem cell deficiency limits the cyclic regenerative capacity of the endometrium and subsequently increases the pregnancy failure rate. Therefore, we hypothesized that PM exposure induces endometrial tissue damage and subsequently reduces the pregnancy rate by inhibiting various beneficial functions of local endometrial stem cells. Consistent with our hypothesis, we showed for the first time that PM exposure significantly inhibits various beneficial functions of endometrial stem cells, such as their self-renewal, transdifferentiation, and migratory capacities, in vitro and in vivo through the PM target gene SERPINB2, which has recently been shown to be involved in multiple stem cell functions. In addition, the PM-induced inhibitory effects on the beneficial functions of endometrial stem cells were significantly diminished by SERPINB2 depletion. Our findings may facilitate the development of promising therapeutic strategies for improving reproductive outcomes in infertile women.
Highlights
Accelerated industrialization and urban development have worsened air pollution, and its harmful effects have become major health concerns in many developed countries[1,2]
Consistent with our hypothesis, we show for the first time that particulate matter (PM) exposure significantly inhibits various beneficial functions of endometrial stem cells, such as their aging, self-renewal, In vitro cell migration assay Cells were plated at 1 × 105 cells/well in 200 μL of culture medium in the upper chambers of Transwell permeable supports (Corning Inc., Corning, NY, USA) to track the migration of cells
PM exposure markedly inhibits various beneficial functions of human endometrial stem cells To evaluate the effects of PM exposure, we isolated human endometrial stem cells from uterine tissue (Supplementary Fig. 1a) and assessed their biological characteristics by analyzing several positive or negative surface markers of stem cells
Summary
Accelerated industrialization and urban development have worsened air pollution, and its harmful effects have become major health concerns in many developed countries[1,2]. Among the various air pollutants, fine particulate matter (PM), which is a mixture of multiple particles, including organic compounds, toxic metals, and crustal elements from different sources[3,4], is a serious international health concern due to its close link to various deleterious effects of air pollution on human health[5,6]. Women exposed to high concentrations of PM during the follicular phase of the menstrual cycle may have an increased risk of miscarriage compared to that of women exposed to low concentrations[8]. In this context, few studies have attempted to explain how PM exposure can trigger female infertility and increase the rate of pregnancy loss[9,10]. The precise mechanisms underlying PM exposure-related female infertility are still poorly understood, probably due to the multiplicity of factors affecting female reproductive function and fertility[11,12,13]
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