Environmental pollutant exposure may play certain roles in the pathogenesis and progression of diabetes mellitus including gestational diabetes mellitus (GDM). We hypothesize that heavy metal exposure may trigger GDM during pregnancy. The objective of this study was to investigate the possible associations between selected heavy metal exposure and GDM risk. This investigation is a retrospective case–control study nested within a cohort of 1359 pregnant women. These participants were recruited in Xiamen Maternity and Child Care Hospital, China, during June to July, 2012. All their newborns’ meconium samples were collected. By reviewing the antenatal care records, 166 GDM mothers were screened out from the 1359 participants; 137 of 166 GDM mothers offered their newborns’ meconium samples for the metal analysis. Those 137 mothers were set as the case group. Similarly, 294 healthy mothers without any gestational complication were initially screened out from the rest 1193 non-GDM mothers. 190 of the 294 healthy mothers offered their newborns’ meconium samples for the metal analysis. Those 190 mothers were set as the control group. Arsenic (As), mercury (Hg), lead (Pb), cadmium (Cd), and chromium (Cr) levels in these case–control meconium samples were measured by inductively coupled plasma mass spectrometry. The possible association between the metal levels and maternal GDM risk of studied subjects was assessed by binary logistic regression. GDM prevalence of 12.21% was observed in the investigated 1359 participants. The concentrations of As, Hg, Cr and Cd in studied cases were significantly higher (p < 0.05) than those of controls. After adjustments for maternal age, pre-pregnant body mass index, gravidity, parity, hepatitis B virus infection, and newborn sex, As, Cd and Cr were found to be positively associated with GDM prevalence in dose-dependent manners. Among them, As was detected in all samples and its levels associated the maternal GDM with the adjusted odds ratios of 3.28 [95% CI 1.24, 8.71], 3.35 [95% CI 1.28, 8.75] and 5.25 [95% CI 1.99, 13.86] for the 2nd, 3rd and 4th quartiles, respectively. The present work implies that exposure to some of the selected metals (noticeably As) may contribute to maternal GDM risk during pregnancy.

Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered.

Nanoplastics (NPs) continue to accumulate in global aquatic and terrestrial systems, posing a potential threat to human health through the food chain and/or other pathways. Both in vivo and in vitro studies have confirmed that the liver is one of the main organs targeted for the accumulation of NPs in living organisms. However, whether exposure to NPs induces size-dependent disorders of liver lipid metabolism remains controversial, and the reversibility of NPs-induced hepatotoxicity is largely unknown. In this study, the effects of long-term exposure to environmentally relevant doses of polystyrene nanoplastics (PS-NPs) on lipid accumulation were investigated in terms of autophagy and lysosomal mechanisms. The findings indicated that hepatic lipid accumulation was more pronounced in mice exposed to 100 nm PS-NPs compared to 500 nm PS-NPs. This effect was effectively alleviated after 50 days of self-recovery for 100 nm and 500 nm PS-NPs exposure. Mechanistically, although PS-NPs exposure activated autophagosome formation through ERK (mitogen-activated protein kinase 1)/mTOR (mechanistic target of rapamycin kinase) signaling pathway, the inhibition of Rab7 (RAB7, member RAS oncogene family), CTSB (cathepsin B), and CTSD (cathepsin D) expression impaired lysosomal function, thereby blocking autophagic flux and contributing to hepatic lipid accumulation. After termination of PS-NPs exposure, lysosomal exocytosis was responsible for the clearance of PS-NPs accumulated in lysosomes. Furthermore, impaired lysosomal function and autophagic flux inhibition were effectively alleviated. This might be the main reason for the alleviation of PS-NPs-induced lipid accumulation after recovery. Collectively, we demonstrate for the first time that lysosomes play a dual role in the persistence and reversibility of hepatotoxicity induced by environmental relevant doses of NPs, which provide novel evidence for the prevention and intervention of liver injury associated with nanoplastics exposure.

Environmental exposure to arsenic, phthalate esters (PAEs) and perfluorinated compounds (PFCs) has been associated with human semen quality. However, the epidemiological "black-box" of these associations remains poorly uncovered. In this study, based on the association analysis between arsenic, PAE and PFC exposure and semen quality parameters (i.e., semen volume, sperm concentration, sperm count, progressive motility, total motility and normal morphology) in a Chinese male population, we explored the seminal plasma metabolic signatures that may mediate the exposure-outcome relations by using the meet-in-metabolite-analysis (MIMA) approach. As a result, a negative association was found between DMA and sperm concentration, whereas MEHP and PFHxS were positively associated with sperm count and concentration, respectively. Metabolomics analysis revealed that sixteen and twenty-two seminal plasma metabolites were related to sperm concentration and count, respectively, and they are mainly involved in fatty acid, lipid and amino acid metabolism. Moreover, it was further indicated that eicosatetraenoate, carnitines and DHA may impact the inverse association between DMA and sperm concentration, while eicosatetraenoate, carnitines, DHA, PGB2 and tocotrienol are possible mediators of the positive association between PFHxS and sperm concentration. As these metabolic biomarkers are relevant to antioxidation and fatty acid β-oxidation, we suggest that redox balance and energy generation shifts in seminal plasma are involved in the association of human semen quality with environmental DMA and PFHxS exposure.