Exposure to Concentrated Ambient PM2.5 Compromises Spermatogenesis in a Mouse Model: Role of Suppression of Hypothalamus-Pituitary-Gonads Axis

Abstract

Epidemiological studies link ambient fine particulate matter (PM2.5) pollution to abnormalities in the male reproductive system. However, few toxicological studies have investigated this potentially important adverse effect of PM2.5 pollution. Therefore, in the present study, we analyzed the effects of PM2.5 exposure on spermatogenesis and hypothalamic-pituitary-gonadal (HPG) axis in a murine model. Fourteen male C57BL/6J mice were subjected to a 4-month exposure to filtered air or concentrated ambient PM2.5 (CAP). Their sperm count, testicular histology, spermatogenic parameters, and the major components of HPG axis were assessed. Exposure to CAP significantly reduced sperm count in the epididymis. This was accompanied by Sertoli cell vacuolization, immature germ cell dislocation, and decreases in pachytene spermatocytes and round spermatids of stage VII seminiferous tubules, suggesting a marked impairment of spermatogenesis in these mice. This impairment of spermatogenesis appeared to be attributable to a suppression of HPG axis subsequent to CAP exposure-induced hypothalamic inflammation, as exposure to CAP significantly increased TNFα and IL1b mRNA levels and meanwhile decreased gonadotropin-releasing hormone mRNA expression in the hypothalamus. Moreover, CAP exposure significantly reduced circulating testosterone and follicle-stimulating hormone, testicular testosterone and mRNA expression of follicle-stimulating hormone target gene SHBG and luteinizing hormone target genes P450scc, 17βHSD, and StAR. The present data demonstrate that exposure to ambient PM2.5 impairs spermatogenesis in murine model, raising the concern over effects of ambient PM2.5 pollution on the male reproductive function.

Fine particle matter disrupts the blood–testis barrier by activating TGF‐β3/p38 MAPK pathway and decreasing testosterone secretion in rat

“…This research showed that PM 2.5 suppressed both serum testosterone and luteinizing hormone levels, which suggested that the adverse effect of PM 2.5 exposure might primarily effect on the secretion of hypothalamus or pituitary resulting in the decrease of reduced luteinizing hormone level. Recent study found that exposure to ambient PM 2.5 significantly reduced circulating testosterone and mRNA expression of luteinizing hormone target genes P450scc, 17bHSD, and StAR. In our study, the testosterone and luteinizing hormone were significantly reduced after PM 2.5 exposure for 30 days, suggesting that endocrine disruptive activity of PM 2.5 may contribute to its reproductive toxicity.…”

“…Recent study found that exposure to ambient PM 2.5 significantly reduced circulating testosterone and mRNA expression of luteinizing hormone target genes P450scc, 17bHSD, and StAR 54 . In our study, the testosterone and luteinizing hormone were significantly reduced after PM 2.5 exposure for 30 days, suggesting that endocrine disruptive activity of PM 2.5 may contribute to its reproductive toxicity.…”

Chronic Exposure to Diesel Exhaust Particulate Matter Impairs Meiotic Progression during Spermatogenesis in a Mouse Model

“…Our gene expression profiling analysis showed not only that the Glycoprotein Hormones, Alpha Polypeptide (Cga), the shared alpha subunit of luteinizing hormone (LH) and follicle stimulating hormone (FSH), is the most remarkable under-expressed gene ( Figure 7A) but also that the GnRH signaling pathway is one of eight significantlyenriched GO terms (Figure 7C). Targeting the HPG axis for PM2.5 exposure to evoke adverse effects on the male reproductive system is consistent with our [15] and others' [23] published studies. Notably, recent studies showed that PM2.5 exposure disrupts the testicular histology and spermatogenesis through a reactive oxygen species (ROS)-dependent mechanism [12,17].…”

Chronic exposure to diesel exhaust particulate matter impairs meiotic progression during spermatogenesis in a mouse model

“…Watanabe and Oonuki showed that inhalation of diesel engine exhaust significantly affects the circulating levels of FSH, LH, testosterone, and estradiol in rats [9]. We recently demonstrated that exposure to concentrated ambient PM2.5 (CAP) influences not only circulating FSH and testosterone but also the hypothalamic expression of GnRH [15]. These studies strongly suggest that the HPG axis may be a crucial mediator for those adverse testicular effects of PM2.5 exposure.…”

“…The sperm count, motility, and morphology are three most frequently used indexes for assessing the quality of semen. To date, studies in various animal models all demonstrate a decrease in the sperm count and motility, if assessed [9][10][11][12][13][14][15][16][17][18]. In contrast, both negative [11,14,[16][17][18] results have been reported regarding the effect of PM2.5 exposure on the rate of morphologically abnormal sperm.…”