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Ambient fine particles (PM 2.5) are known to cause various reproductive and developmental diseases. However, the potential mechanisms of PM 2.5 exposure induced female reproductive damage remain unclear. Four weeks old female C57BL/6 J mice were exposed to filtered air (FA, n = 10) or concentrated ambient PM 2.5 (CAP, n = 10) using a versatile aerosol concentration enrichment system. After 9 weeks of the exposure, mice were sacrificed under sevoflurane anesthesia and tissue samples were collected. Immunohistochemical analysis, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, and RNA-sequencing were performed to analyze the effects of PM 2.5 exposure on follicle development and elucidate its potential mechanisms. Chronic PM 2.5 exposure resulted in follicular dysplasia. Compared to the FA-exposed group, follicular atresia in the CAP-exposed mice were significantly increased. Further studies confirmed that CAP induced apoptosis in granulosa cells, accompanied by a distortion of hormone homeostasis. In addition, RNA-sequencing data demonstrated that CAP exposure induced the alteration of ovarian gene expressions and was associated with inflammatory response. Chronic exposure to CAP can induce follicular atresia, which was associated with hormone modulation and inflammation. [Display omitted] • PM 2.5 exposure induced follicular atresia in female mice. • PM 2.5 exposure promoted granulosa cell apoptosis in the atretic follicles. • PM 2.5 exposure disturbed hormone homeostasis. • PM 2.5 exposure triggered inflammatory response in mouse ovary. [ABSTRACT FROM AUTHOR]

Ambient fine particulate matter (PM 2.5) consists of various components, and their respective contributions to the toxicity of PM 2.5 remains to be determined. To provide specific recommendations for preventing adverse effects due to PM 2.5 pollution, we determined whether the induction of pulmonary inflammation, the putative pathogenesis for the morbidity and mortality due to PM 2.5 exposure, was fractioned through solubility-dependent fractioning. In the present study, the water and heptane solubilities-dependent serial fractioning of diesel exhaust particulate matter (DEP), a prominent source of urban PM 2.5 pollution, was performed. The pro-inflammatory actions of these resultant fractions were then determined using both an intratracheal instillation mouse model and cultured BEAS-2B cells, a human bronchial epithelial cell line. Instillation of the water-insoluble, but not -soluble fraction elicited significant pulmonary inflammatory and acute phase responses, comparable to those induced by instillation of DEP. The water-insoluble fraction was further fractioned using heptane, a polar organic solvent, and instillation of heptane-insoluble, but not -soluble fraction elicited significant pulmonary inflammation and acute phase responses. Furthermore, we showed that DEP and water-insoluble DEP, but not water-soluble DEP, activated pro-inflammatory signaling in cultured BEAS-2B cells, ruling out the possibility that the solubility impacts the in vivo distribution and thus the pulmonary inflammatory response. ● The water-soluble constitutes in DEP has almost no toxicological effects in cells. ● Water-insoluble but not soluble fraction was responsible for PM 2.5 -induced pulmonary inflammation and acute phase response. ● The heptane-insoluble fraction contributes most to the PM 2.5 -induced inflammation and acute phase response in lung. [ABSTRACT FROM AUTHOR]

Ambient fine particulate matter (PM 2.5) exposure correlates with adverse cardiometabolic effects. The underlying mechanisms have not yet been fully understood. Hypothalamic-pituitary-adrenal (HPA) axis, as the central stress response system, regulates cardiometabolic homeostasis and is implicated in the progression of various adverse health effects caused by inhalational airborne pollutant exposure. In this study, we investigated whether ambient PM 2.5 exposure activates HPA axis and its effect mediating PM 2.5 -induced pulmonary inflammation. C57Bl/6 J mice were intratracheally instilled with different concentrations of diesel exhaust PM 2.5 (DEP), and plasma was harvested at different times. Assessments of plasma stress hormones revealed that DEP instillation dose- and time-dependently increased mouse circulating corticosterone and adrenocorticotropic hormone (ACTH) levels, strongly supporting that DEP instillation activates HPA axis. To determine which components of DEP activate HPA axis, C57Bl/6J mice were intratracheally instilled with water-soluble and -insoluble fractions of DEP. Plasma analyses showed that water-insoluble but not -soluble fraction of DEP increased circulating corticosterone and ACTH levels. Consistently, concentrated ambient PM 2.5 (CAP) exposure significantly increased mouse urine and hair corticosterone levels, corroborating the activation of HPA axis by ambient PM 2.5. Furthermore, deletion of stress hormones by total bilateral adrenalectomy alleviated PM 2.5 -induced pulmonary inflammation, providing insights into the contribution of central neurohormonal mechanisms in modulating adverse health effects caused by exposure to PM 2.5. • DEP exposure dose and time-dependently affects corticosterone and ACTH levels. • Water-insoluble but not soluble component of DEP contributes to HPA axis activation. • Chronic CAP exposure significantly increases mouse urine and hair corticosterone levels. • Deletion of stress hormones alleviated PM 2.5 -induced pulmonary inflammation. [ABSTRACT FROM AUTHOR]