Abstract

BackgroundFine particulate matter (PM2.5) exposure accelerates atherosclerosis and contains known ovotoxic chemicals. However, effects of exposure to PM2.5 on the finite ovarian follicle pool have hardly been investigated, nor have interactions between ovarian and cardiovascular effects. We hypothesized that subchronic inhalation exposure to human-relevant concentrations of PM2.5 results in destruction of ovarian follicles via apoptosis induction, as well as accelerated recruitment of primordial follicles into the growing pool. Further, we hypothesized that destruction of ovarian follicles enhances the adverse cardiovascular effects of PM2.5 in females.ResultsHyperlipidemic apolipoprotein E (Apoe) null ovary-intact or ovariectomized female mice and testis-intact male mice were exposed to concentrated ambient PM2.5 or filtered air for 12 weeks, 5 days/week for 4 h/day using a versatile aerosol concentration enrichment system. Primordial, primary, and secondary ovarian follicle numbers were decreased by 45%, 40%, and 17%, respectively, in PM2.5-exposed ovary-intact mice compared to controls (P < 0.05). The percentage of primary follicles with granulosa cells positive for the mitosis marker Ki67 was increased in the ovaries from PM2.5-exposed females versus controls (P < 0.05), consistent with increased recruitment of primordial follicles into the growing pool. Exposure to PM2.5 increased the percentages of primary and secondary follicles with DNA damage, assessed by γH2AX immunostaining (P < 0.05). Exposure to PM2.5 increased the percentages of apoptotic antral follicles, determined by TUNEL and activated caspase 3 immunostaining (P < 0.05). Removal of the ovaries and PM2.5-exposure exacerbated the atherosclerotic effects of hyperlipidemia in females (P < 0.05). While there were statistically significant changes in blood pressure and heart rate variability in PM2.5-compared to Air-exposed gonad-intact males and females and ovariectomized females, the changes were not consistent between exposure years and assessment methods.ConclusionsThese results demonstrate that subchronic PM2.5 exposure depletes the ovarian reserve by increasing recruitment of primordial follicles into the growing pool and increasing apoptosis of growing follicles. Further, PM2.5 exposure and removal of the ovaries each increase atherosclerosis progression in Apoe-/- females. Premature loss of ovarian function is associated with increased risk of osteoporosis, cardiovascular disease and Alzheimer’s disease in women. Our results thus support possible links between PM2.5 exposure and other adverse health outcomes in women.

Highlights

  • Fine particulate matter ­(PM2.5) exposure accelerates atherosclerosis and contains known ovotoxic chemicals

  • Luderer et al Particle and Fibre Toxicology (2022) 19:5 males and females and ovariectomized females, the changes were not consistent between exposure years and assessment methods. These results demonstrate that subchronic ­PM2.5 exposure depletes the ovarian reserve by increasing recruitment of primordial follicles into the growing pool and increasing apoptosis of growing follicles

  • Similar to many other urban areas worldwide, P­ M2.5 from human activities in southern California’s South Coast Air Basin is mainly composed of ammonium nitrate from atmospheric chemical reactions of oxides of nitrogen from mobile and stationary combustion sources, elemental and organic carbon compounds from combustion sources, and ammonium sulfate from atmospheric chemical reactions of sulfur oxides from combustion sources [1]. ­PM2.5 are regulated in the United States under the Clean Air Act National Ambient Air Quality Standards (NAAQS)

Read more

Summary

Introduction

Fine particulate matter ­(PM2.5) exposure accelerates atherosclerosis and contains known ovotoxic chemicals. Effects of exposure to ­PM2.5 on the finite ovarian follicle pool have hardly been investigated, nor have interactions between ovarian and cardiovascular effects. We hypothesized that subchronic inhalation exposure to human-relevant concentrations of ­PM2.5 results in destruction of ovarian follicles via apoptosis induction, as well as accelerated recruitment of primordial follicles into the growing pool. We hypothesized that destruction of ovarian follicles enhances the adverse cardiovascular effects of ­PM2.5 in females. The ovarian follicle, which consists of the oocyte surrounded by specialized somatic cells, is the functional unit of the ovary. The ovaries do not possess germline stem cells in postnatal life, and females are born with a finite complement of oocytes, which are packaged in primordial follicles [3, 4]. POF/POI is associated with increased risk of cardiovascular disease, Alzheimer’s disease, and osteoporosis [5,6,7,8]

Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call