The impact of fine particulate matter (PM) on various beneficial functions of human endometrial stem cells through its key regulator SERPINB2

Abstract

Reproductive health: Pollution is problematic for female fertility Airborne pollutants may reduce female fertility through their debilitating effects on the stem cells that maintain the endometrium, the interior lining of the uterus. Recent evidence suggests that toxic byproducts from fossil fuels known as 'particulate matter' represent a danger to women's reproductive health. South Korean researchers led by Ji-Won Jung, Korea Centers for Disease Control and Prevention, and In-Sun Hong, Gachon University, Incheon, have investigated this risk by exposing cultured human endometrial stem cells to diesel-derived particulate matter. These stem cells normally maintain the endometrium, allowing embryonic implantation to take place, but exposure to particulate matter greatly impaired the cells' regenerative function. Mice exposed to particulate matter exhibited similar impairments of endometrial maintenance. The researchers identified a molecular pathway associated with this response that could guide development of fertility-restoring treatments. 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.