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

Abstract

Fine particle matter (PM) is correlated with male reproductive dysfunction in animals and humans, but the underlying mechanisms remain unknown. To investigate the toxic mechanism of PM, 32 male Sprague-Dawley (SD) rats were exposed to saline or PM with the doses of 1.8, 5.4, and 16.2 mg/kg.b.w. via intratracheal instillation, respectively, one time every 3 days, in total times for 30 days. Sperm concentration, hormone level, the expressions of BTB-associated protein and the mitogen-activated protein kinase (MAPK) pathway, tumor necrosis factor α and transforming growth factor β3 levels were detected. The results showed a decrease in sperm number, testosterone and luteinizing hormone levels and altered ultrastructure of BTB in testis of rat after exposure to PM . The protein levels of N-Cadherin, Occludin, Claudin-11, and Connexin-43 were significantly decreased in the testes. TGF-β3 content in testes showed increase, with the p-p38/p38 MAPK ratio also increasing after PM exposure. These results demonstrate that PM restrained the expressions of BTB-associated proteins through activating TGF-β3/p38 MAPK pathway and decreasing testosterone secretion, and therefore lead to the damage of BTB resulting in the decrease of sperm quality, which might be the potential reasons for its negative effects on spermatogenesis and male reproduction.

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

“…The lack of effect on the rate of abnormal sperm is supported by our present data showing that chronic exposure to DEP did not increase the rates of stillbirth and absorption (Table 1), and also consistent with our [15] and others' [9,13,18,20] published data. However, in contrast to the very consistent published data regarding the adverse effects of PM2.5 exposure on the sperm count and motility [9,[13][14][15]17,18,20,21], there are several published studies showing that exposure to PM2.5 increases the rate of abnormal sperm [14,17,21]. Although the reason for this confliction of published data regarding the effect of PM2.5 exposure on the rate of abnormal sperm remains to be determined, it somehow suggests a composition-dependency for this particular effect 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.…”

“…The integrity of the blood-testis barrier (BTB) is essential for spermatogenesis. Several studies show that exposure to PM2.5 results in a disruption of the BTB [10][11][12][13]16], providing a potential mechanism for the spermatogenic abnormalities induced by PM2.5 exposure. In addition, exposure to PM2.5 was shown to evoke reactive oxygen species (ROS) production [12,17], inflammation [18], and endoplasmic reticulum (ER) stress [14] in the testes, suggesting that these may also be local mediators for the spermatogenic abnormalities induced by PM2.5 exposure.…”

Effects of Parental Smoking on Occurrence of Childhood Acute Leukemia

“…On the other hand, evidence that paternal smoking has serious adverse effects on the functional and morphological quality of sperm is increasing [31], with even secondhand smoking causing germline mutations [32,33]. Moreover, tobacco smoke contains fine particulate matter [34,35] that can disrupt blood-testis barrier to accelerate the action of genotoxic chemicals in tobacco smoke in addition to its own influence on sperm qualities [36,37]. Thus, the effects of paternal smoking on the occurrence of childhood cancers may be related to the effects of tobacco smoke on sperm.…”

Air Pollution and COVID-19: A Possible Dangerous Synergy for Male Fertility

“…Regarding the mechanism of endocrine disruptors, chronic exposure to PM2.5 in animal models has demonstrated a significant decrease in follicle-stimulating hormone (FSH), low circulating testosterone levels and consequent reduction in sperm concentration through suppression of the hypothalamus−pituitary−gonad axis (HPG) [ 39 , 40 ].…”