Climate match is key to predict range expansion of the world's worst invasive terrestrial vertebrates.

Understanding the determinants of the range expansion of invasive alien species is crucial for developing effective prevention and control strategies. Nevertheless, we still lack a global picture of the potential factors influencing the invaded range expansion across taxonomic groups, especially for the world's worst invaders with high ecological and economic impacts. Here, by extensively collecting data on 363 distributional ranges of 19 of world's worst invasive terrestrial vertebrates across 135 invaded administrative jurisdictions, we observed remarkable variations in the range expansion across species and taxonomic groups. After controlling for taxonomic and geographic pseudoreplicates, model averaging analyses based on generalized additive mixed-effect models showed that species in invaded regions having climates more similar to those of their native ranges tended to undergo a larger range expansion. In addition, as proxies of propagule pressure and human-assisted transportation, the number of introduction events and the road network density were also important predictors facilitating the range expansion. Further variance partitioning analyses validated the predominant role of climate match in explaining the range expansion. Our study demonstrated that regions with similar climates to their native ranges could still be prioritized to prevent the spread of invasive species under the sustained global change.

Social media unveils the hidden but high magnitude of human-mediated biological invasions in China.

Humans are responsible for the release of many non-native animals into the wild. However, these releases occur randomly and are difficult to monitor. Here, using two of the worst invasive herpetofauna as model taxa, we applied an iEcology approach and found a high magnitude of human-mediated releases in China, suggesting this approach can be used to monitor introductions and advise management bodies in a timely manner.

Vulnerability of protected areas to future climate change, land use modification, and biological invasions in China.

Anthropogenic climate change, land use modifications, and alien species invasions are major threats to global biodiversity. Protected areas (PAs) are regarded as the cornerstone of biodiversity conservation, however, few studies have quantified the vulnerability of PAs to these global change factors together. Here, we overlay the risks of climate change, land use change, and alien vertebrate establishment within boundaries of a total of 1020 PAs with different administrative levels in China to quantify their vulnerabilities. Our results show that 56.6% of PAs will face at least one stress factor, and 21 PAs are threatened under the highest risk with three stressors simultaneously. PAs designed for forest conservation in Southwest and South China are most sensitive to the three global change factors. In addition, wildlife and wetland PAs are predicted to mainly experience climate change and high land use anthropogenetic modifications, and many wildlife PAs can also provide suitable habitats for alien vertebrate establishment. Our study highlights the urgent need for proactive conservation and management planning of Chinese PAs by considering different global change factors together.

Verapamil Regulates the Macrophage Immunity to Mycobacterium tuberculosis through NF-κB Signaling.

BACKGROUND: Verapamil enhances the sensitivity of Mycobacterium tuberculosis to anti-tuberculosis (TB) drugs, promotes the macrophage anti-TB ability, and reduces drug resistance, but its mechanism is unclear. Herein, we have investigated the effect of verapamil on cytokine expression in mouse peritoneal macrophages. METHODS: Macrophages from mice infected with M. tuberculosis or S. aureus were cultured with verapamil, the cytokines were detected by enzyme-linked immunosorbent assay, and the RNA was measured with quantitative real-time polymerase chain reaction and agarose gel electrophoresis. The intracellular calcium signaling was measured by confocal microscopy. RESULTS: Significantly higher levels of NF-κB, IL-12, TNF-α, and IL-1ß were observed after TB infection. The levels of NF-κB and IL-12 increased when verapamil concentration was less than 50 µg/ml, but decreased when verapamil concentration was greater than 50µg/ml. With the increase in verapamil concentration, TNF-α and IL-1ß expressed by macrophages decreased. The L-type calcium channel transcription significantly increased in M. tuberculosis rather than S. aureus-infected macrophages. Furthermore, during bacillus Calmette-Guerin (BCG) infection, verapamil stimulated a sharp peak in calcium concentration in macrophages, while calcium concentration increased mildly and decreased smoothly over time in the absence of verapamil. CONCLUSION: Verapamil enhanced macrophage immunity via the NF-κB pathway, and its effects on cytokine expression may be achieved by its regulation of intracellular calcium signaling.

Dioxin-like polychlorinated biphenyl 126 (PCB126) disrupts gut microbiota-host metabolic dysfunction in mice via aryl hydrocarbon receptor activation.

Exposure to environmental pollutants, including dioxin-like pollutants, can cause numerous health issues. A common exposure route to pollutants is through contaminated foods, and thus the gastrointestinal system and gut microbiota are often exposed to high amounts of pollutants. Multiple studies have focused on the imbalance in intestinal microbiota composition caused by dioxin-like pollutants. Here, we examined the effects of polychlorinated biphenyl 126 (PCB126) on the composition and functions of gut microbes through metagenomic sequencing, and explored the correlations between microflora dysbiosis and aryl hydrocarbon receptor (AHR) signaling. Adult male wild-type and Ahr-/- mice with a C57BL/6 background were weekly exposed to 50 µg/kg body weight of PCB126 for 8 weeks. Results showed that PCB126 had the opposite effect on gut microbiota composition and diversity in the wild-type and Ahr-/- mice. Functional prediction found that PCB126 exposure mainly altered carbon metabolism and signal regulatory pathways in wild-type mice but impacted DNA replication and lipopolysaccharide biosynthesis in Ahr-/- mice. In wild-type mice, PCB126 exposure induced liver injury, decreased serum lipid content, and delayed gastrointestinal motility, which were significantly correlated to several specific bacterial taxa, such as Helicobacter. Following AHR knockout, however, the holistic effects of PCB126 on the host were lessened or abolished. These results suggest that PCB126 may disrupt host metabolism and gut microbiota dynamics via AHR activation. Overall, our findings provide new insight into the complex interactions between host metabolism and gut microbiota, which may contribute to grouped assessment of environmental pollutants in the future.

Biological invasions facilitate zoonotic disease emergences.

Outbreaks of zoonotic diseases are accelerating at an unprecedented rate in the current era of globalization, with substantial impacts on the global economy, public health, and sustainability. Alien species invasions have been hypothesized to be important to zoonotic diseases by introducing both existing and novel pathogens to invaded ranges. However, few studies have evaluated the generality of alien species facilitating zoonoses across multiple host and parasite taxa worldwide. Here, we simultaneously quantify the role of 795 established alien hosts on the 10,473 zoonosis events across the globe since the 14th century. We observe an average of ~5.9 zoonoses per alien zoonotic host. After accounting for species-, disease-, and geographic-level sampling biases, spatial autocorrelation, and the lack of independence of zoonosis events, we find that the number of zoonosis events increase with the richness of alien zoonotic hosts, both across space and through time. We also detect positive associations between the number of zoonosis events per unit space and climate change, land-use change, biodiversity loss, human population density, and PubMed citations. These findings suggest that alien host introductions have likely contributed to zoonosis emergences throughout recent history and that minimizing future zoonotic host species introductions could have global health benefits.

Low-dose PCB126 exposure disrupts cardiac metabolism and causes hypertrophy and fibrosis in mice.

The residue of polychlorinated biphenyls (PCBs) exists throughout the environment and humans are subject to long-term exposure. As such, the potential environmental and health risk caused by low-dose exposure to PCBs has attracted much attention. 3, 3', 4, 4', 5-pentachlorobiphenyl (PCB126), the highest toxicity compound among dioxin-like-PCBs, has been widely used and mass-produced. Cardiotoxicity is PCB126's crucial adverse effect. Maintaining proper metabolism underlies heart health, whereas the impact of PCB126 exposure on cardiac metabolic patterns has yet to be elucidated. In this study, we administered 0.5 and 50 µg/kg bw of PCB126 to adult male mice weekly by gavage for eight weeks. Pathological results showed that low-dose PCB126 exposure induced heart injury. Metabolomic analysis of the heart tissue exposed to low-dose PCB126 identified 59 differential metabolites that were involved in lipid metabolism, amino acid metabolism, and the tricarboxylic acid (TCA) cycle. Typical metabolomic characteristic of cardiac hypertrophy was reflected by accumulation of fatty acids (e.g. palmitic, palmitoleic, and linoleic acid), and disturbance of carbohydrates including D-glucose and intermediates in TCA cycle (fumaric, succinic, and citric acid). Low-dose PCB126 exposure increased glycine and threonine, the amino acids necessary for the productions of collagen and elastin. Besides, PCB126-exposed mice exhibited upregulation of collagen synthesis enzymes and extracellular matrix proteins, indicative of cardiac fibrosis. Moreover, the expression of genes related to TGFß/PPARγ/MMP-2 signaling pathway was perturbed in the PCB126-treated hearts. Together, our results reveal that low-dose PCB126 exposure disrupts cardiac metabolism correlated with hypertrophy and fibrosis. This study sheds light on the underlying mechanism of PCBs' cardiotoxicity and identifies potential sensitive biomarkers for environmental monitoring.

Perfluoropolyether carboxylic acids (novel alternatives to PFOA) impair zebrafish posterior swim bladder development via thyroid hormone disruption.

Perfluoropolyether carboxylic acids (PFECAs, CF3(OCF2)nCOO-, n = 2-5) are novel alternatives to perfluorooctanoic acid (PFOA) and are widely used in industrial production. However, although they have been detected in surface water and human blood, their toxicities on aquatic organisms remain unknown. We used zebrafish embryos to compare the developmental toxicities of various PFECAs (e.g., perfluoro (3,5,7-trioxaoctanoic) acid (PFO3OA), perfluoro (3,5,7,9-tetraoxadecanoic) acid (PFO4DA), and perfluoro (3,5,7,9,11-pentaoxadodecanoic) acid (PFO5DoDA)) with that of PFOA and to further reveal the key events related to toxicity caused by these chemicals. Results showed that, based on half maximal effective concentrations (EC50), toxicity increased in the order: PFO5DoDA > PFO4DA > PFOA > PFO3OA, with uninflated posterior swim bladders the most frequently observed malformation. Similar to PFOA, PFECA exposure significantly lowered thyroid hormone (TH) levels (e.g., T3 (3,5,3'-L-triiodothyronine) and T4 (L-thyroxine)) in the whole body of larvae at 5 d post-fertilization following disrupted TH metabolism. In addition, the transcription of UDP glucuronosyltransferase 1 family a, b (ugt1ab), a gene related to TH metabolism, increased dose-dependently. Exogeneous T3 or T4 supplementation partly rescued PFECA-induced posterior swim bladder malformation. Our results further suggested that PFECAs primarily damaged the swim bladder mesothelium during early development. This study is the first to report on novel emerging PFECAs as thyroid disruptors causing swim bladder malformation. Furthermore, given that PFECA toxicity increased with backbone OCF2 moieties, they may not be safer alternatives to PFOA.

Accumulation, Biotransformation, and Endocrine Disruption Effects of Fluorotelomer Surfactant Mixtures on Zebrafish.

As an alternative to perfluorooctanesulfonate (PFOS), novel fluorotelomer surfactants (6:2 fluorotelomer sulfonamide alkylbetaine (6:2 FTAB) and 6:2 fluorotelomer sulfonamide alkylamine (6:2 FTAA)) are widely used in aqueous film-forming foams and are frequently found to coexist in the environment. However, their potential toxicities remain unknown. Here, we investigated the chronic toxicity of 6:2 FTAB (65%) and 6:2 FTAA (35%) coexposure on adult zebrafish at doses of 0, 5, 50, or 500 µg/L using a flow-through exposure system for 180 days. Results showed that 6:2 FTAB was undetected in adult tissue and their offspring, while 6:2 FTAA was highly dominant, accounting for ∼92% of total quantified poly/perfluoroalkyl substances (PFASs), and their metabolic products (6:2 fluorotelomer sulfonamide and 6:2 fluorotelomer sulfonate) further accounting for 2.8%-8.5%. 6:2 FTAA accumulation exhibited a sex-bias, with higher levels found in male livers than that in female, but in gonad showed an opposite pattern. Co-exposure to 6:2 FTAB and 6:2 FTAA mixture (50 and 500 µg/L) could decrease the average number of eggs production and increase the malformation and mortality in their offspring. Testosterone (T) and 17 ß-estradiol (E2) levels increased in the 50 and 500 µg/L exposed females, but T level decreased in the 500 µg/L exposed males. Correspondingly, the transcriptional pattern of hypothalamus-pituitary-gonad axis genes was different between male and female. Increased liver vitellogenin levels in the 50 and 500 µg/L-exposed males indicated that these compounds might possess estrogen-like activity. Furthermore, 3,5,3'-triiodothyronine (T3) and thyroxine (T4) levels decreased in the 50 and 500 µg/L females and increased T4 level in 500 µg/L exposed males. These results suggest that 6:2 FTAB is extensively metabolized in fish, whereas 6:2 FTAB and 6:2 FTAA coexposure disrupted the adult endocrine system and impaired offspring development.

Induction of hepatic miR-34a by perfluorooctanoic acid regulates metabolism-related genes in mice.

Perfluorooctanoic acid (PFOA) is a widespread organic pollutant with various toxicological impacts on the liver. Members of the miR-34 family are P53-targeted growth suppressors. We found that PFOA exposure (5 mg/kg/d PFOA for 28 d) resulted in a significant increase of miR-34a in the livers of mice but had no effect on either miR-34b or miR-34c. We knocked out miR-34a in mice to explore the role of elevated miR-34a in PFOA-induced liver toxicity. Compared with the corresponding untreated control, significant increases in liver weight as well as serum alanine transaminase, aspartate aminotransferase, and cholinesterase levels were observed in miR-34a-/- and wild-type mice after PFOA exposure. Hepatic cells showed similar swelling in both miR-34a-/- and wild-type mice after PFOA treatment. Hepatic RNA-sequencing (RNA-seq) showed that PFOA led to significant alteration in lipid metabolism genes, especially those involved in the peroxisome proliferator-activated receptor pathway, in both wild-type and miR-34a null mice. With or without PFOA treatment, relatively fewer genes were altered in miR-34a-/- livers compared to wild-type livers. Among the changed genes by miR-34a, the most dominant were metabolism-related genes, such as Fabp3, Cyp7a1, and Apoa4. Our in vivo study indicated that miR-34a mainly exerts a metabolic regulation role, rather than the pro-apoptosis and cell cycle arrest role reported previously by many in vitro studies. In addition, although hepatic P53 was unchanged, the active type of P53 (acetylated P53 (acetyl-p53, Lys379)) was markedly altered under PFOA treatment. Therefore, the increase in acetylated P53 may have activated the transcription of miR-34a in mouse livers after PFOA treatment.

Subchronic Hepatotoxicity Effects of 6:2 Chlorinated Polyfluorinated Ether Sulfonate (6:2 Cl-PFESA), a Novel Perfluorooctanesulfonate (PFOS) Alternative, on Adult Male Mice.

The compound 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), an alternative to perfluorooctanesulfonate (PFOS) in the metal-plating industry, has been widely detected in various environmental matrices. However, its hepatotoxicity has yet to be clarified. Here, male mice were exposed to 0.04, 0.2, or 1 mg/kg/day of 6:2 Cl-PFESA for 56 days. Results demonstrated that relative liver weight increased significantly in the 0.2 and 1 mg/kg/day 6:2 Cl-PFESA groups, whereas liver lipid accumulation increased in all 6:2 Cl-PFESA groups. Serum enzyme activities of alanine transaminase and alkaline phosphatase were increased. Serum triglycerides and low-density lipoprotein cholesterol both increased, whereas serum total cholesterol and high-density lipoprotein cholesterol decreased following 6:2 Cl-PFESA exposure. A total of 264 differentially expressed proteins (127 up-regulated and 137 down-regulated), mainly involved in lipid metabolism, xenobiotic metabolism, and ribosome biogenesis, were identified by quantitative proteomics. Bioinformatics analysis highlighted the de-regulation of PPAR and PXR, which may contribute to the hepatotoxicity of 6:2 Cl-PFESA. Additionally, 6:2 Cl-PFESA induced both cell apoptosis and proliferation in the mouse liver. Compared to the overt toxicity of PFOS, 6:2 Cl-PFESA exhibited more-serious hepatotoxicity. Thus, caution should be exercised in the application of 6:2 Cl-PFESA as a replacement alternative to PFOS in industrial areas.

Subchronic reproductive effects of 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFAES), an alternative to PFOS, on adult male mice.

With a similar structure to perfluorooctane sulfonate (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFAES) has been widely used as a mist suppressant in the chromium plating industry in China since the 1970s. After being disregarded for the past 30 years, 6:2 Cl-PFAES has now been detected in environmental matrices and human sera, suggesting potential health concerns. We carried out a subchronic exposure study to investigate the reproductive toxicity of 6:2 Cl-PFAES exposure (0, 0.04, 0.2, and 1.0 mg/kg/d body weight, 56 d) in adult male BALB/c mice. Results showed that relative epididymis and testis weights decreased in the 1.0 mg/kg/d group compared with the control. However, no changes were observed in the serum levels of testosterone, estradiol, follicle-stimulating hormone (FSH), or luteinizing hormone (LH), nor in the histopathological structure of the epididymis and testis and sperm count. In addition, 56 d of consecutive gavage of 1.0 mg/kg/d of 6:2 Cl-PFAES did not affect male mouse fertility. RNA sequencing showed that no genes were significantly altered in the testes after 6:2 Cl-PFAES exposure. Several testicular genes, which are sensitive to PFOS exposure, were also detected using Western blotting, and included steroidogenic proteins, STAR, CYP11A1, CYP17A1, and 3ß-HSD and cell junction proteins, occludin, ß-catenin, and connexin 43; however, none were changed after 6:2 Cl-PFAES exposure. Except for a decrease in the relative epididymis and testis weights in the 1.0 mg/kg/d group, 6:2 Cl-PFAES exposure for 56 d exerted no significant effect on the serum levels of reproductive hormones or the testicular mRNA profilesin adult male mice, implying a relative weak reproductive injury potential compared with that of PFOS.

Cytotoxicity of novel fluorinated alternatives to long-chain perfluoroalkyl substances to human liver cell line and their binding capacity to human liver fatty acid binding protein.

Although shorter chain homologues and other types of fluorinated chemicals are currently used as alternatives to long-chain perfluoroalkyl substances (PFASs), their safety information remains unclear and urgently needed. Here, the cytotoxicity of several fluorinated alternatives (i.e., 6:2 fluorotelomer carboxylic acid (6:2 FTCA), 6:2 fluorotelomer sulfonic acid (6:2 FTSA), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), and hexafluoropropylene oxide (HFPO) homologues) to human liver HL-7702 cell line were measured and compared with perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Their binding mode and affinity to human liver fatty acid binding protein (hL-FABP) were also determined. Compared with PFOA and PFOS, 6:2 Cl-PFESA, HFPO trimer acid (HFPO-TA), HFPO tetramer acid (HFPO-TeA), and 6:2 FTSA showed greater toxic effects on cell viabilities. At low exposure doses, these alternatives induced cell proliferation with similar mechanism which was different from that of PFOA and PFOS. Furthermore, binding affinity to hL-FABP decreased in the order of 6:2 FTCA < 6:2 FTSA < HFPO dimer acid (HFPO-DA) < PFOA < PFOS/6:2 Cl-PFESA/HFPO-TA. Due to their distinctive structure, 6:2 Cl-PFESA and HFPO homologues were bound to the hL-FABP inner pocket with unique binding modes and higher binding energy compared with PFOA and PFOS. This research enhances our understanding of the toxicity of PFAS alternatives during usage and provides useful evidence for the development of new alternatives.

Dietary exposure to di-isobutyl phthalate increases urinary 5-methyl-2'-deoxycytidine level and affects reproductive function in adult male mice.

Phthalates are a large family of ubiquitous environmental pollutants suspected of being endocrine disruptors. Epidemiological studies have associated phthalate metabolites with decreased reproductive parameters and linked phthalate exposure with the level of urinary 5-methyl-2'-deoxycytidine (5mdC, a product of methylated DNA). In this study, adult male mice were exposed to 450mg di-isobutyl phthalate (DiBP)/(kg·day) via dietary exposure for 28days. Mono-isobutyl phthalate (MiBP, the urinary metabolite) and reproductive function parameters were determined. The levels of 5mdC and 5-hydroxymethyl-2'-deoxycytidine (5hmdC) were measured in urine to evaluate if their contents were also altered by DiBP exposure in this animal model. Results showed that DiBP exposure led to a significant increase in the urinary 5mdC level and significant decreases in sperm concentration and motility in the epididymis, accompanied with reduced testosterone levels and down-regulation of the P450 cholesterol side-chain cleavage enzyme (P450scc) gene in the mice testes. Our findings indicated that exposure to DiBP increased the urinary 5mdC levels, which supported our recent epidemiological study about the associations of urinary 5mdC with phthalate exposure in the male human population. In addition, DiBP exposure impaired male reproductive function, possibly by disturbing testosterone levels; P450scc might be a major steroidogenic enzyme targeted by DiBP or other phthalates.

Inhibition effects of perfluoroalkyl acids on progesterone production in mLTC-1.

Perfluoroalkyl substances (PFASs) are a class of fluorine substituted carboxylic acid, sulfonic acid and alcohol, structurally similar to their corresponding parent compounds. Previous study demonstrated the potential endocrine disruption and reproductive toxicity of perfluorooctane sulfonic acid and perfluorooctanoic acid, two dominant PFASs in animals and humans. We explored the relationship between eleven perfluoroalkyl acids (PFAAs) with different carbon chain length and their ability to inhibit progesterone production in mouse Leydig tumor cells (mLTC-1). We found an obvious dose-response relationship between progesterone inhibition rate and PFAA exposure concentration in mLTC-1. The relative inhibition rate of progesterone by PFAAs was linearly related to the carbon chain length and molar refractivity of PFAAs. Mitochondrial membrane potential (MMP) decreased after PFAA exposure at the half-maximal inhibitory effect concentration (IC50) of progesterone production in mLTC-1, while the reactive oxygen species (ROS) content increased significantly. These results imply that the inhibition effect of PFAAs on progesterone production might be due, in part, to ROS damage and the decrease in MMP in mLTC-1.

Acot1 is a sensitive indicator for PPARα activation after perfluorooctanoic acid exposure in primary hepatocytes of Sprague-Dawley rats.

Perfluorooctanoic acid (PFOA) is one of the most commonly detected and persistent perfluoroalkyl substances (PFASs) found in the environment. We found that cell viability and intracellular oxidant stress increased in primary rat hepatocytes exposed to PFOA (100µM PFOA, 24h), and mitochondrial superoxide increased from 6.25µM PFOA treatment group. To screen for sensitive indicators in mRNA level, we investigated global transcriptome profile alteration after PFOA exposure using RNA-sequencing (RNA-seq) in primary rat hepatocytes, and identified 177 gene transcripts (158 upregulated, 19 downregulated) as significantly changed after exposure to 100µM of PFOA for 24h (fold change ≥2, FDR<0.05). Quantitative PCR (qPCR) and RNA-fluorescence in situ hybridization (RNA-FISH) assays were conducted after PFOA treatment at various doses (0, 0.4, 1.56, 6.25, 25, and 100µM) and times (6, 12, 18, 24, 48, and 96h). Acot1 transcripts increased significantly in the 100µM PFOA group (4500-fold) after 24h of exposure, and increased remarkably for all time points (24, 48, 72 and 96h) after exposure to 6.25µM. Acot1 also responded to lower PFOA doses, with a significant increase found after exposure to 0.4µM for 96h. These results imply Acot1 could serve as a sensitive indicator for PPARα activation after PFOA exposure in primary rat hepatocytes.

Gestational and lactational exposure to di-isobutyl phthalate via diet in maternal mice decreases testosterone levels in male offspring.

Phthalates are a large family of ubiquitous environmental chemicals suspected of being endocrine disruptors, with exposure to these chemicals during prenatal and postnatal development possibly resulting in reproductive disorders. Di-isobutyl phthalate (DiBP) is widely used in consumer and industrial products, and although its exposure in the general population has increased in recent years, the mechanisms behind DiBP-induced reproductive disorders in male offspring remain unclear. Here, pregnant mice were exposed to 0 or 450 mg/kg bw/day DiBP via diet from gestation day (GD) 0 to GD21. Until postnatal day 21 (PD21), half of the exposed pups were also exposed to DiBP by lactation (TT), while the rest were not (TC). Half of each group were sacrificed on PD21, with the remaining mice fed a normal diet until PD80 (TCC and TTC, respectively). Reproductive toxicological parameters such as relative organ weights and testosterone levels were determined in male offspring on PD21 and PD80 and sperm quality was tested on PD80. Maternal exposure (pregnancy and lactation) led to decreased serum and testis testosterone concentrations, accompanied by decreased expression of 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and cytochrome P450 family 11 subfamily A member 1 (CYP11A1) in PD21 pups and PD80 adults. Furthermore, the TTC group showed decreased epididymis sperm concentration and motility. Taken together, DiBP exposure in early life (prenatal and postnatal) impaired male reproductive function in later life, possibly by interfering with testosterone levels and CYP11A1, which might be a major steroidogenic enzyme targeted by DiBP or other phthalates.

RNA-sequencing analysis reveals the hepatotoxic mechanism of perfluoroalkyl alternatives, HFPO2 and HFPO4, following exposure in mice.

The toxicological impact of traditional perfluoroalkyl chemicals has led to the elimination and restriction of these substances. However, many novel perfluoroalkyl alternatives remain unregulated and little is known about their potential effects on environmental and human health. Daily administration of two alternative perfluoroalkyl substances, HFPO2 and HFPO4 (1 mg kg-1 body weight), for 28 days resulted in hepatomegaly and hepatic histopathological injury in mice, particularly in the HFPO4 group. We generated and compared high-throughput RNA-sequencing data from hepatic tissues in control and treatment group mice to clarify the mechanism of HFPO2 and HFPO4 hepatotoxicity. We identified 146 (101 upregulated, 45 downregulated) and 1295 (716 upregulated, 579 downregulated) hepatic transcripts that exhibited statistically significant changes (fold change ≥2 or ≤0.5, false discovery rate < 0.05) after HFPO2 and HFPO4 treatment, respectively. Among them, 111 (82 upregulated, 29 downregulated) transcripts were changed in both groups, and lipid metabolism associated genes were dominant. Thus, similar to their popular predecessors, HFPO2 and HFPO4 exposure exerted hepatic effects, including hepatomegaly and injury, and altered lipid metabolism gene levels in the liver, though HFPO4 exerted greater hepatotoxicity than HFPO2. The unregulated use of these emerging perfluoroalkyl alternatives may affect environmental and human health, and their biological effects need further exploration. Copyright © 2016 John Wiley & Sons, Ltd.

Gestational and lactational exposure to bisphenol AF in maternal rats increases testosterone levels in 23-day-old male offspring.

During prenatal and postnatal development, exposure to environmental chemicals with estrogenic activity, such as bisphenol AF (BPAF), may result in reproductive disorders. Currently, the mechanisms behind such disorders in male offspring induced by gestational and lactational exposure to BPAF remain poorly understood. Here, female rats from gestational day (GD) 3-19 were exposed to 100 mg BPAF/kg/day by oral gavage. On the day of birth (postnatal day (PD) 0), cross-fostering took place between treated and control litters, and cross-fostered mother rats were given BPAF 100 mg/kg/day during the postnatal period (PD 3 to PD 19). HPLC-MS/MS analysis showed that BPAF was transferred via cord blood and lactation, finally bio-accumulating in the offspring testes. Pups exposed to BPAF both prenatally and postnatally showed a significant increase in testis testosterone levels compared with that of the control, while all pups exposed to BPAF showed a significant decrease in testis inhibin B (INHB) levels. Compared with the control, RNA-seq revealed that 279 genes were significantly differentially expressed in the testes of pups exposed to BPAF both prenatally and postnatally, including genes involved in cell differentiation and meiosis. These results indicate that gestational and lactational exposure to BPAF in the mother can impair reproductive function in male offspring.