Spatial distribution and accumulation profiles of volatile methylsiloxanes in Tokyo Bay, Japan: Mass loadings and historical trends.

We investigated mass loading and the spatial distribution of volatile methylsiloxanes (VMSs) including four cyclic VMSs (D3-D6; cVMSs, the number refers to the number of SiO bonds) and three linear VMSs (L3-L5; lVMSs) in Tokyo Bay, Japan, which is one of the most industrialized, urbanized, and populated areas in the world. Based on the VMS concentrations determined in eight main inflow rivers to the bay, the mass loading of VMSs via inflow rivers and sewage treatment plants located in Tokyo Bay was estimated at 2500 kg/y for total VMSs. Elevated mass loadings of VMSs were found in three of the rivers, inflowing to the inner west of Tokyo Bay. The distribution and deposition characteristics of VMSs were observed depending on the estuarine condition. Estuarine sediments were found to be efficient and effective traps for VMSs and the salting-out effect is one possible mechanism to explain this phenomenon. The overall profiles of D4, D5, and D6 in surface water and sediment were observed across Tokyo Bay; elevated concentrations were identified in the inner west bay with dispersed low concentrations in the outer bay, except for one hotspot of D4 in the sediment, indicating a major emission route of VMSs via inflow rivers. Additionally, the historical pollution profiles of VMSs in Tokyo Bay were reconstructed based on the VMS concentrations determined in a dated sediment core. VMSs were identified throughout the upper 40 cm of the sediment core (representing the mid 1980s); the profiles correspond with the historical use of VMSs in wash-off personal care-products. The noted decreasing trend of D4 might be a reflection of the early 2000s replacement of D4 with D5 in such products. The elevated VMS concentrations in the estuarine sediment raise concerns about the impact on the aquatic environment.

Occurrence and Trophodynamics of Marine Lipophilic Phycotoxins in a Subtropical Marine Food Web.

Marine lipophilic phycotoxins (MLPs) are produced by toxigenic microalgae and cause foodborne illnesses. However, there is little information on the trophic transfer potential of MLPs in marine food webs. In this study, various food web components including 17 species of mollusks, crustaceans, and fishes were collected for an analysis of 17 representative MLPs, including azaspiracids (AZAs), brevetoxins (BTXs), gymnodimine (GYM), spirolides (SPXs), okadaic acid (OA), dinophysistoxins (DTXs), pectenotoxins (PTXs), yessotoxins (YTXs), and ciguatoxins (CTXs). Among the 17 target MLPs, 12, namely, AZAs1-3, BTX3, GYM, SPX1, OA, DTXs1-2, PTX2, YTX, and the YTX derivative homoYTX, were detected, and the total MLP concentrations ranged from 0.316 to 20.3 ng g-1 wet weight (ww). The mean total MLP concentrations generally decreased as follows: mollusks (8.54 ng g-1, ww) > crustaceans (1.38 ng g-1, ww) > fishes (0.914 ng g-1, ww). OA, DTXs, and YTXs were the predominant MLPs accumulated in the studied biota. Trophic dilution of the total MLPs was observed with a trophic magnification factor of 0.109. The studied MLPs might not pose health risks to residents who consume contaminated seafood; however, their potential risks to the ecosystem can be a cause for concern.

Antagonistic interaction between perfluorobutanesulfonate and probiotic on lipid and glucose metabolisms in the liver of zebrafish.

Perfluorobutanesulfonate (PFBS) and probiotic bacteria can interact to induce hepatic hypertrophy. However, the molecular events occurring in the hypertrophic liver are still unknown. Therefore, we performed this follow-up study using adult zebrafish that were exposed for 40 days to 0 and 10 µg/L PFBS, with or without dietary supplementation of probiotic Lactobacillus rhamnosus. After PFBS or/and probiotic exposures, proteome perturbation, histological pathogenesis and glucose metabolism were investigated in the livers. Proteomic analysis showed potent intervention of PFBS or/and probiotic with hepatic functions. PFBS single exposure caused marked disturbances in lipid metabolisms, which may underlie the severe vacuolization in male liver. The addition of probiotic alleviated the lipid metabolic disorders of PFBS. Furthermore, probiotic supplementation enhanced ATP energy production using glucose in mitochondrial respiratory chain of male fish. However, PFBS alone caused remarkable increase in blood glucose level (by 2.5-fold relative to the control), underlining the onset of hyperglycemia symptom. In contrast, the liver of male fish from the coexposure group functioned appropriately, which immediately increased insulin levels by 2.2-fold to reduce the glucose accumulation in blood. In female liver, PFBS alone significantly decreased the blood glucagon concentration by 2.9-fold. The deficiency of glucagon hormone consequently contributed to the accumulation of glycogen (3.2-fold) therein. Vigorous antagonistic interaction between PFBS and probiotic was noted with respect to glucose metabolism, which restored ATP, glucose, glycogen and glucagon to the control levels. Overall, the present study finds that probiotic L. rhamnosus is efficient to mitigate the metabolic disorders of PFBS on lipid and glucose, highlighting the potential values of probiotic bacteria to protect the aquatic ecosystem.

Target, Nontarget, and Suspect Screening and Temporal Trends of Per- and Polyfluoroalkyl Substances in Marine Mammals from the South China Sea.

Per- and polyfluoroalkyl substances (PFASs) have been manufactured and widely used for over 60 years. Currently, there are thousands of marketed PFASs, but only dozens of them are routinely monitored. This work involved target, nontarget, and suspect screening of PFASs in the liver of Indo-Pacific humpback dolphin (Sousa chinensis) and finless porpoise (Neophocaena phocaenoides), two resident marine mammals in the South China Sea, stranded between 2012 and 2018. Among the 21 target PFASs, perfluorooctane sulfonate and 6:2 chlorinated polyfluoroalkyl ether sulfonate (6:2 Cl-PFESA) predominated in the samples, accounting for 46 and 30% of the total PFASs, respectively. Significantly higher total target PFAS concentrations (p < 0.05) were found in dolphin liver samples [3.23 × 103 ± 2.63 × 103 ng/g dry weight (dw)] than in porpoise liver samples (2.63 × 103 ± 1.10 × 103 ng/g dw). Significant increasing temporal trends (p < 0.05) were found in the concentrations of two emerging PFASs, perfluoroethylcyclohexane sulfonate and 2,3,3,3-tetrafluoro-2-propanoate in porpoises, indicating increasing pollution by these emerging PFASs. Forty-four PFASs from 9 classes were additionally identified by nontarget and suspect screening, among which 15 compounds were reported for the first time in marine mammals. A primary risk assessment showed that the emerging PFAS 6:2 Cl-PFESA could have possible adverse effects in terms of reproductive injury potential on most of the investigated cetaceans.

Disturbances in Microbial and Metabolic Communication across the Gut-Liver Axis Induced by a Dioxin-like Pollutant: An Integrated Metagenomics and Metabolomics Analysis.

To determine how the aryl hydrocarbon receptor (AhR) signaling acts along the gut-liver axis, we employed an integrated metagenomic and metabolomic approach to comprehensively profile the microbial and metabolic networks. Adult zebrafish were exposed to a model agonist of the AhR: polychlorinated biphenyl (PCB) 126. The metagenomic analysis showed that PCB126 suppressed microbial activities related to primary bile acid metabolism in male intestines. Accordingly, a suite of primary bile acids consistently showed higher concentrations, suggesting that bacterial conversion of primary bile acids was blocked. PCB126 also disturbed bacterial metabolism of bile acids in female intestines, as revealed by higher concentrations of primary bile acids (e.g., chenodeoxycholic acid) and activation of the nuclear farnesoid X receptor signaling. In addition, PCB126 exposure impaired the metabolism of various essential vitamins (e.g., retinol, vitamin B6, and folate). Degradation of vitamin B6 by bacterial enzymes was inhibited in male intestines, resulting in its intestinal accumulation. However, PCB126 suppressed the bacterial metabolism of vitamins in female intestines, causing systematic deficiency of essential vitamins. Overall, we found that PCB126 exposure dysregulated gut microbial activities, consequently interrupting bile acid and vitamin metabolism along the gut-liver axis. The findings provided an insight of the AhR action in microbe-host metabolic communication related to PCBs.

Binary exposure to hypoxia and perfluorobutane sulfonate disturbs sensory perception and chromatin topography in marine medaka embryos.

Perfluorobutane sulfonate (PFBS), an environmental pollutant of emerging concern, is previously shown to dynamically interact with hypoxia on aquatic developmental toxicities. However, the molecular mechanisms underlying the interaction remain unknown. In this follow-up study, marine medaka embryos were exposed to 0 and 3.3 mg/L of PFBS under normoxia (6.9 mg/L) or hypoxia (1.7 mg/L) condition till 15 days post-fertilization. High-throughput transcriptomic sequencing was employed to filter differentially expressed genes and provide mechanistic insight into interactive action between hypoxia and PFBS. The results showed that hypoxia alone and the coexposure paradigm were similarly potent to modify transcriptional profiles, with the majority of genes significantly down-regulated. In contrast, transcriptional toxicity of PFBS was relatively milder. Functional annotation analyses found that hypoxia and coexposure groups mainly impacted phototransduction signaling by decreasing the transcriptions of cyclic nucleotide-gated (CNG) cation channels and retinol transport genes. However, this study demonstrated the first toxicological evidence that toxic effects of PFBS targeted the perception of chemical stimulus through olfactory and gustatory receptors. The addition of PFBS moderately exacerbated the toxic actions of hypoxia, which largely shaped the transcriptional pattern of coexposure group. In addition, gene interactive networks were constructed for hypoxia and coexposure groups, underlining the increased chromatin deacetylation and methylation to epigenetically repress genome-wide transcriptional initiation. Overall, PFBS and hypoxia interact to interrupt the embryonic development of sensory systems, which may compromise the individual fitness and survival, especially during early life stages when precocious perception of food and escape from predators are essential.

Blood partitioning and whole-blood-based maternal transfer assessment of chlorinated paraffins in mother-infant pairs from South China.

As a new group of persistent organic pollutants of concern, chlorinated paraffins (CPs) have been widely detected in the environment and biota, but their occurrence, partitioning, and transfer in humans have been not well documented. In this study, 32 pairs of maternal blood, cord blood, and placenta samples were collected from pregnant women in South China, and the blood was further separated into plasma and red blood cells (RBCs) for blood partitioning study. Short- and medium-chain CPs (SCCPs and MCCPs, respectively) were detected in all the five human biological matrices, suggesting prevalent exposure and maternal transfer of CPs in the pregnant women. Discrepant congener group profiles of CPs were observed in different human biological matrices. Significant differences in the plasma-RBC partitioning of CPs in the maternal and cord bloods were identified (p < 0.001). CP partitioning to plasma was stronger than that to RBCs in maternal blood, but the converse was true for cord blood. Mass fractions in plasma (Fp) for SCCPs (mean, 0.78) and MCCPs (0.74) in maternal blood were significantly higher than the values in cord blood. Transplacental transfer efficiencies (TTEs) were evaluated based on the whole blood concentrations of CPs in the maternal and cord bloods, and the TTEs ranged from 0.50 to 0.69 (first to third quartiles) for SCCPs and MCCPs, indicating that the placenta can partially restrict maternal transfer. The extent of CP retention in the placenta was assessed by the concentration ratio (RPM) of matched placenta and maternal blood, and interestingly, a U-shaped trend for placental retention (RPM) with increasing chain length was observed for individual congener groups. Significant relationships of the CP concentrations among the maternal blood, cord blood, and placenta were observed (p < 0.001). To our knowledge, this is the first study to report the plasma-RBC partitioning of CPs in human maternal and cord bloods, as well as the first study to evaluate TTEs based on whole blood concentrations. Our study confirmed that whole blood is the preferred matrix for accurately assessing human internal exposure and transplacental transfer of CPs.

Probiotic modulation of perfluorobutanesulfonate toxicity in zebrafish: Disturbances in retinoid metabolism and visual physiology.

Perfluorobutanesulfonate (PFBS), an aquatic pollutant of emerging concern, is found to disturb gut microbiota, retinoid metabolism and visual signaling in teleosts, while probiotic supplementation can shape gut microbial community to improve retinoid absorption. However, it remains unknown whether probiotic bacteria can modulate the toxicities of PFBS on retinoid metabolism and visual physiology. In the present study, adult zebrafish were exposed for 28 days to 0, 10 and 100 µg/L PFBS, with or without dietary administration of probiotic Lactobacillus rhamnosus. Interaction between PFBS and probiotic was examined regarding retinoid dynamics (intestine, liver and eye) and visual stimuli transmission. PFBS single exposures remarkably inhibited the absorption of retinyl ester in female intestines, which were, however, restored by probiotic to normal status. Although coexposure scenarios markedly increased the hepatic storage of retinyl ester in females, mobilization of retinol was reduced in livers by single or combined exposures regardless of sex. In the eyes, transport and catalytic conversion of retinol to retinal and retinoic acid were interrupted by PFBS alone, which were efficiently antagonized by probiotic presumably through an indirect action. In response to the availability of retinal chromophore, transcriptions of opsins and arrestin genes were altered adaptively to control visual perception and termination. Neurotransmission across retina circuitry was changed accordingly, centering on epinephrine and norepinephrine. In summary, the present study found the efficient modulation of probiotic on retinoid metabolic disorders of PFBS pollution, which subsequently impacted visual signaling. A future work is warranted to provide mechanistic clues in retinoid interaction.

Parental exposure to perfluorobutane sulfonate disturbs the transfer of maternal transcripts and offspring embryonic development in zebrafish.

Parental exposure to perfluorobutane sulfonate (PFBS), an aquatic pollutant of emerging concern, is previously found to impair the embryonic development of offspring. However, the impairing mechanisms remain to clarify. In the present study, adult zebrafish were exposed to 0, 10 and 100 µg/L PFBS for 28 d, after which disturbances in maternal transcript transfer and offspring embryogenesis were investigated. Prior to zygotic genome activation, high-throughput transcriptomic sequencing revealed that parental PFBS exposure significantly altered the transcript profile of maternal origin in offspring eggs, while toxic actions varied as a function of PFBS concentrations. In offspring eggs derived from 10 µg/L exposure group, differential transcripts were mainly associated with the histone-DNA interaction of nucleosome, which would modify the compacted chromatin configuration and accessibility of transcriptional factors to DNA sequences. In this regard, the timing of zygotic genome activation was presumably disrupted. Parental exposure to 100 µg/L PFBS primarily interrupted the maternal transfer of adherens junction transcripts, which was supposed to dysregulate the cell-cell adhesion during early embryo formation. Development and growth of offspring embryos were significantly compromised by parental PFBS exposure, as exemplified by higher mortality, delayed hatching, slower heart rate, reduced body weight and neurobehavioral disorders. Overall, the present study presented the first toxicological evidence about the disturbances of PFBS in maternal transcript transfer, although the inherent linkage between maternal transcript modifications and offspring development defects still needs future works to construct.

Dietary administration of probiotic Lactobacillus rhamnosus modulates the neurological toxicities of perfluorobutanesulfonate in zebrafish.

Perfluorobutanesulfonate (PFBS), an aquatic pollutant of emerging concern, is found to disturb the neural signaling along gut-brain axis, whereas probiotic additives have been applied to improve neuroendocrine function of teleosts. Both PFBS and probiotics can commonly target nervous system. However, whether and how probiotic bacteria can modulate the neurotoxicities of PFBS remain not explored. It is thus necessary to elucidate the probiotic modulation of PFBS neurotoxicity, which can provide implications to the application of probiotic bacteria in aquaculture industry. In the present study, adult zebrafish were exposed to 0, 10 and 100 µg/L PFBS with or without dietary administration of probiotic Lactobacillus rhamnosus. Interaction between PFBS and probiotic along gut-brain axis was examined, covering three dominant pathways (i.e., neurotransmission, immune response and hypothalamic-pituitary-adrenal (HPA) axis). The results showed that, compared to the single effects, PFBS and probiotic coexposure significantly altered the acetylcholinesterase activity and neurotransmitter profiles in gut and brain of zebrafish, with mild effects on neuronal integrity. Neurotransmitters closely correlated reciprocally in intestines, which, however, was distinct from the correlation profile in brains. In addition, PFBS and probiotic were combined to impact brain health through absorption of bacterial lipopolysaccharides and production of inflammatory cytokines. Relative to neurotransmission and immune signaling, HPA axis was not involved in the neurotoxicological interaction between PFBS and probiotic. Furthermore, it needs to point out that interactive modes between PFBS and probiotic varied a lot, depending on exposure concentrations, sex and toxic indices. Overall, the present study provided the first evidence that probiotic supplement could dynamically modulate the neurotoxicities of PFBS in teleost.

Unexpected Observations: Probiotic Administration Greatly Aggravates the Reproductive Toxicity of Perfluorobutanesulfonate in Zebrafish.

The present study exposed adult zebrafish to 0, 10, and 100 µg/L perfluorobutanesulfonate (PFBS) with or without dietary supplement of probiotic Lactobacillus rhamnosus. Interaction between probiotic and PFBS on sex endocrine and reproduction was investigated. It was striking to find that PFBS and probiotic coexposures almost ceased the fecundity, which was accompanied by disturbances in sex hormones and oocyte maturation in females. In contrast, probiotic additive efficiently antagonized the estrogenic activity of PFBS in males. For the first time, this study reported that probiotic heavily depended on sex to modulate the endocrine disruption and reproductive toxicity of aquatic pollutants.

Probiotic Modulation of Lipid Metabolism Disorders Caused by Perfluorobutanesulfonate Pollution in Zebrafish.

To determine whether and how probiotic supplement can alter gut microbiota dysbiosis and lipid metabolism disorders caused by perfluorobutanesulfonate (PFBS), the present study exposed adult zebrafish to 0, 10, and 100 µg/L PFBS for 28 days, with or without dietary administration of probiotic Lactobacillus rhamnosus. Regarding intestinal health and gut microbiota, probiotic supplement altered the innate toxicities of PFBS, depending on exposure concentration and the sex of the fish. Lactobacillus genus correlated positively (P < 0.001; r > 0.5) with other beneficial bacteria in the gut microbiota, thereby indirectly regulating host metabolic activities. In female fish, the PFBS and probiotic combination enhanced fatty acid synthesis and ß-oxidation, but mitigated the accumulation of cholesterol in the blood compared with PFBS single exposure, highlighting the benefits of the probiotic to host health. In male zebrafish, probiotic administration antagonized the PFBS-induced disturbances of bile acid metabolism, presumably via farnesoid X receptor signaling. However, coexposure to PFBS and probiotic caused significant accumulation of triglyceride in male livers (2.6-fold relative to the control), implying the induction of hepatic steatosis. Overall, the present study underlined the potential of probiotics to modulate gut microbial dysbiosis and lipid metabolism disorders caused by PFBS exposure, which could provide implications to the application of probiotics in aquaculture.

Enantiomer-specific bioaccumulation and distribution of chiral pharmaceuticals in a subtropical marine food web.

There is a growing concern about the occurrence of chiral pharmaceuticals in the aquatic environment. However, trophic transfer of pharmaceutical enantiomers in marine organisms is still largely unknown. This study assessed the bioaccumulation and spatial distribution of four frequently detected pharmaceuticals - atenolol, metoprolol, venlafaxine, and chloramphenicol, in a subtropical marine food web in Hong Kong waters. Twenty-four species were analyzed, including mollusks, crustaceans, and fishes. Special focus was placed in the chirality of the four analytes comprising ten different stereoisomers. Results showed that mean concentrations of individual pharmaceuticals ranged from <0.03 to 5.88 ng/g wet weight, and invertebrates generally had higher concentrations than fishes. Organisms from Hong Kong western waters were likely more contaminated by the studied pharmaceuticals than those from southern and eastern waters. Trophic dilution was observed for atenolol and chloramphenicol, with trophic magnification factors of 0.164 and 0.517, respectively. R-(+)-atenolol, S-(-)-metoprolol, and R-(-)-venlafaxine were selectively accumulated in fishes, and stereoisomeric impurities of chloramphenicol, i.e., enantiomers apart from R,R-para-form, were widespread in the investigated species. Under the worst-case scenario, atenolol and metoprolol in collected fishes might exceed toxic threshold, while local adults were unlikely to experience health risks from pharmaceutical exposure via seafood consumption.

Interaction between hypoxia and perfluorobutane sulfonate on developmental toxicity and endocrine disruption in marine medaka embryos.

The co-occurrence of hypoxia and xenobiotics is extremely common in natural environments, highlighting the necessity to elicit their interaction on aquatic toxicities. In the present study, marine medaka embryos were exposed to various concentrations (nominal 0, 1, 3.3 and 10 mg/L) of perfluorobutane sulfonate (PFBS), an environmental pollutant of emerging concern, under either normoxia (6.9 mg/L) or hypoxia (1.7 mg/L) condition. After acute exposure till 15 days post-fertilization, single or combined toxicities of PFBS and hypoxia on embryonic development (e.g., mortality, hatching and heartbeat) and endocrine systems were investigated. Sex and thyroid hormones were measured by enzyme-linked immunosorbent assay. Transcriptional changes of endocrine genes were determined by quantitative real-time PCR assays. Co-exposure to 10 mg/L PFBS and hypoxia caused a further reduction in survival rate and heart beat compared to single exposure. PFBS induced a precocious hatching, while no larvae hatched under hypoxia condition. By disturbing the balance of sex hormones, either PFBS or hypoxia single exposure produced an anti-estrogenic activity in medaka larvae. However, PFBS and hypoxia combinations reversed to estrogenic activity in co-exposed larvae. Variation in disrupting pattern may be attributed to the interactive effects on steroidogenic pathway involving diverse cytochrome P450 enzymes. Regarding thyroid system, PFBS exposure caused detriments of multiple processes along thyroidal axis (e.g., feedback regulation, synthesis and transport of thyroid hormones, receptor-mediated signaling and thyroid gland development), while hypoxia potently impaired the development and function of thyroid gland. Combinations of PFBS and hypoxia interacted to dysregulate the function of thyroid endocrine system. In summary, the present study revealed the dynamic interaction of PFBS pollutant and hypoxia on aquatic developmental toxicities and endocrine disruption. Considering the frequent co-occurrence of xenobiotics and hypoxia, current results would be beneficial to improve our understanding about their interactive mechanisms and provide baseline evidences for accurate ecological risk evaluation.

Activation of aryl hydrocarbon receptor by dioxin directly shifts gut microbiota in zebrafish.

Gut microbiota is of critical importance to host health. Aryl hydrocarbon receptor (AhR) is found to be closely involved in the regulation of gut microbial dynamics. However, it is still not clear how AhR signaling shapes the gut microbiota. In the present study, adult zebrafish were acutely exposed to an AhR antagonist (CH223191), an AhR agonist (polychlorinated biphenyl 126; PCB126) or their combination for 7 d. Overall intestinal health and gut microbial community were temporally monitored (1 d, 3 d and 7 d) and inter-compared among different groups. The results showed that single exposure to PCB126 significantly disrupted the overall health of intestines (i.e., neural signaling, inflammation, epithelial barrier integrity, oxidative stress). However, CH223191 failed to inhibit but enhanced the physiological toxicities of PCB126, implying the involvement of extra mechanisms rather than AhR in the regulation of intestinal physiological activities. Dysbiosis of gut microbiota was also caused by PCB126 over time as a function of sex. It is intriguing that CH223191 successfully abolished the holistic effects of dioxin on gut microbiota, which inferred that growth of gut microbes was directly controlled by AhR activation without the involvement of host feedback modulation. When coming to detailed alterations at certain taxon, both antagonistic and synergistic interactions existed between CH223191 and dioxin, depending on fish sex, exposure duration and bacterial species. Correlation analysis found that gut inflammation was positively associated with pathogenic Legionella bacteria, but was negatively associated with epithelial barrier integrity, suggesting that integral intestinal epithelial barrier can prevent the influx of pathogenic bacteria to induce inflammatory response. Overall, this study has deciphered, for the first time, the direct regulative effects of AhR activity on gut microbiota. Future research is warranted to elucidate the specific mechanisms of AhR action on certain bacterial population.

Prevalence, Biotransformation, and Maternal Transfer of Synthetic Phenolic Antioxidants in Pregnant Women from South China.

Synthetic phenolic antioxidants (SPAs) have been identified as an emerging group of contaminants in recent years. However, there are significant gaps in our knowledge of human prenatal exposure to these synthetic chemicals. In this study, a set of eight SPAs and four major transformation products (TPs) were systematically analyzed in matched samples of maternal plasma, cord plasma, and placenta from a population of pregnant women. Five of the eight target SPAs and all four target TPs were frequently detected in the maternal-placental-fetal unit, indicating prenatal exposure to SPAs and the transfer of SPAs across the placenta. In the three matrices, 2,6-di-tert-butyl-hydroxytoluene (BHT), 2,4-di-tert-butylphenol (DBP), and 2,2'-methylenebis(4-methyl-6-tert-butylphenol) (AO 2246) were identified as the most abundant SPAs, while 2,6-di-tert-butyl-1,4-benzoquinone (BHT-Q) and 2,6-di-tert-butyl-4-hydroxy-4-methyl-2,5-cyclohexadienone (BHT-quinol) were identified as the predominant TPs of BHT. In the maternal plasma, concentrations of both BHT-Q and BHT-quinol were significantly correlated with BHT (p < 0.001), suggesting that the two TPs mainly originated from the biotransformation of BHT itself in pregnant women. The transplacental transfer efficiencies (TTEs) of the SPAs and TPs were structure-dependent and generally less than 1. Significantly higher TTEs for four target TPs than their parent BHT were identified. To our knowledge, this study provides the first evidence that SPAs and TPs transfer across the placenta in pregnant women.

Parental Exposure to Perfluorobutanesulfonate Impairs Offspring Development through Inheritance of Paternal Methylome.

Perfluorobutanesulfonate (PFBS), an environmental pollutant of emerging concern, significantly impairs offspring development and overall health after parental exposure. However, the true inducer of offspring developmental defects among the complexity of parental influences remains unknown. In the present study, marine medaka (Oryzias melastigma) were exposed to environmentally realistic concentrations of PFBS (0, 1, 3, and 10 µg/L) for an entire life cycle. By mixing and mating control and exposed medaka (male or female), a crossbreeding strategy was employed to produce offspring eggs from various crossbreeds, with the aim of differentiating the maternal and paternal influences. Measurements of swimming performance in larval offspring showed that larvae of exposed male parents swam hyperactively in comparison to the control larvae. Contrasting trends in PFBS transfer and maternal factor transfer (e.g., proteins and lipids) to that of swimming behavior eliminated these two factors as major inducers of offspring developmental impairment. Inheritance of the exposed paternal methylome marks in offspring may be partially responsible for abnormal swimming behavior, although different toxic mechanisms may be involved depending on the exposure concentration. Overall, these findings suggest that inheritance of epigenetic modifications implicates a long-lasting threat of PFBS to the fitness and sustainability of fish populations.

Occurrence and Distribution of Photoinitiator Additives in Paired Maternal and Cord Plasma in a South China Population.

Photoinitiators (PIs) are widely used in industrial polymerization and have been detected as emerging contaminants in environmental matrixes. It has been reported that humans are exposed to PIs, but the maternal-fetal transmission of PIs has not been documented. In this study, we analyzed 21 PIs (9 benzophenones, BZPs; 8 amine co-initiators, ACIs; and 4 thioxanthones, TXs) in matched maternal-cord plasma samples from 49 pregnant women in South China. Sixteen of the 21 target PIs were found in maternal plasma at concentrations of ∑PIs (sum of the detected PIs) from 303 to 3500 pg/mL. Meanwhile, 12 PIs were detected in cord plasma with ∑PIs from 104 to 988 pg/mL. The PIs detected in both maternal and cord plasma samples were dominated by BZPs, followed by ACIs and TXs. Different groups of PIs showed structure-dependent placental transfer efficiencies (PTEs). The PTEs were generally less than 100% for BZPs but greater than 100% for ACIs and TXs. By further theoretical calculation, we revealed the critical structural features of PIs that affect PTEs. This is the first study to investigate the occurrence and distribution of PIs in paired maternal and cord plasma, and it sheds light on the potential mechanism of structure-dependent placental transfer.

Perfluorobutanesulfonate Exposure Skews Sex Ratio in Fish and Transgenerationally Impairs Reproduction.

Perfluorobutanesulfonate (PFBS) is increasingly polluting aquatic environments due to worldwide manufacturing and application. However, toxicological knowledge regarding PFBS exposure remains scarce. Here, we showed that PFBS life-cycle exposure at environmentally realistic concentrations (0, 1.0, 2.9, and 9.5 µg/L) skewed the sex ratio in fish toward male dominance, while reproductive functions of female fish were greatly impaired, as characterized by extremely small ovaries, blocked oocyte development, and decreased egg production. Endocrine disruption through the hypothalamus-pituitary-gonad axis was induced by PFBS exposure, showing antiestrogenic activity in females but estrogenic activity in males. PFBS was found to gradually accumulate in F0 adults during continuous exposure but can be rapidly eliminated when depurated in clean water. Parental exposure also transferred PFBS pollutant to F1 offspring eggs. Although no trace of PFBS was detected in F1 adults and F2 eggs, adverse effects from parental exposure persisted in F1 and F2 offspring. These transgenerational effects implicate PFBS as an ongoing threat to the fitness and sustainability of fish populations. The dramatic impairment of fish reproduction highlights the urgency of re-evaluations of the ecological and evolutionary consequences of PFBS exposure.