Public concern over the health implications of antimicrobials employed in aquaculture has resulted in adoption of strict regulations for their use. This study employed a high-throughput protocol covering 86 compounds in six pharmaceutical groups to screen feed and sediments from 20 tilapia ponds randomly in 18 farms of an aquacultural unit in southern China, one of important tilapia fillet suppliers in the world. Seventeen samples of commercial feeds from manufacturer-sealed bags in the farms were tetracyclines-free but not antibiotic-free. All the sealed-bag feeds contained quinolones and two feeds had sulfonamides (up to 140 μg kg⁻¹). Meanwhile, seven leftover-feeds in opened bags contained added antimicrobials: tetracyclines (570–2790 μg kg⁻¹) in all and florfenicol (20–294 μg kg⁻¹) in four. All the feeds regardless sealed or not had large amounts (221–2642 μg kg⁻¹) of salicylic acid (possible antimicrobial substitute) and caffeine, and one sealed-bag feed even was quantified with medroxyprogesterone. Surface sediments (0–10 cm) from the ponds were detected with 36 compounds and sublayer sediments (10–20) with 8 compounds. Large amounts of salicylic acid were present in both surface and sublayer sediments accounting up to 10% of total pharmaceutical residues. Surface sediments were dominated by antibiotics (5.2–172 μg kg⁻¹), mainly sulfonamides and quinolones, contributing 68% of the total quantitative compound mass. Sublayer sediments were also enriched in quinolones (up to 260 μg kg⁻¹). Surprisingly, all sediments contained progesterone (up to 8.0 μg kg⁻¹) in coincidence to the feed with medroxyprogesterone, perhaps arising from endocrine abuses or cross-contamination. Although high levels of other pharmacologic residues (caffeine) in sediment posed greater than medium ecological risks, antibiotic residues contributed only 2–35% to the risk. These findings suggest that antibiotic-free feed may be insufficient to control antibiotic abuse in aquaculture and that additional regulatory actions may be necessary, such as veterinary prescription as human antibiotic uses.

Embryonic exposure to environmental chemicals may result in specific chronic diseases in adulthood. Parabens, a type of environmental endocrine disruptors widely used in pharmaceuticals and cosmetics, have been shown to cause a decline in women's reproductive function. However, whether exposure to parabens during pregnancy also negatively affect the ovarian function of the female offspring in adulthood remains unclear. This study aims to investigate the effects of prenatal propylparaben (PrP) exposure on the ovarian function of adult mice aged 46 weeks, which is equivalent to the age of 40 years in women. Pregnant ICR mice were intraperitoneally injected with human-relevant doses of PrP (i.e., 0, 7.5, 90, and 450 mg/kg/day) during the fetal sex determination period—from embryonic day E7.5 to E13.5. Our results revealed that ovarian aging was accelerated in PrP-exposed mice at 46 weeks, with altered regularity of the estrous cycle, decreased serum estrogen (E2) and progesterone (P4) levels, reduced size of the primordial follicle pool, and increased number of atretic follicles. It was found that prenatal exposure to human-relevant doses of PrP exacerbated ovarian oxidative stress, inflammation, and fibrosis, which promoted follicular atresia by activating the mitochondrial apoptosis pathway. To compensate, the depletion of primordial follicles was also accelerated by activating the PI3K/AKT/mTOR signaling pathway in PrP-exposed mice. Moreover, PrP induced hypermethylation of CpG sites in the promoter region of Cyp11a1 (a 17.16–64.28% increase) partly led to the disrupted steroidogenesis, and the altered methylation levels of imprinted genes H19 and Peg3 may also contribute to the phenotypes observed. These remarkable findings highlight the embryonic origin of ovarian aging and suggest that a reduced use of PrP during pregnancy should be advocated.

Perfluorooctane sulfonate (PFOS), an artificial perfluorinated compound, has been associated with male reproductive disorders. Histone modifications are important epigenetic mediators; however, the impact of PFOS exposure on testicular steroidogenesis through histone modification regulations remains to be elucidated. In this study, we examined the roles of histone modifications in regulating steroid hormone production in male rats chronically exposed to low-level PFOS. The results indicate that PFOS exposure significantly up-regulated the expressions of StAR, CYP11A1 and 3β-HSD, while CYP17A1 and 17β-HSD were down-regulated, thus contributing to the elevated progesterone and testosterone levels. Furthermore, PFOS significantly increased the histones H3K9me2, H3K9ac and H3K18ac while reduced H3K9me3 in rat testis. It is known that histone modifications are closely involved in gene transcription. Therefore, to investigate the association between histone modifications and steroidogenic gene regulation, the levels of these histone marks were further measured in steroidogenic gene promoter regions by ChIP. It was found that H3K18ac was augmented in Cyp11a1 promoter, and H3K9ac was increased in Hsd3b after PFOS exposure, which is proposed to result in the activation of CYP11A1 and 3β-HSD, respectively. To sum up, chronic low-level PFOS exposure activated key steroidogenic gene expression through enhancing histone acetylation (H3K9ac and H3K18ac), ultimately stimulating steroid hormone biosynthesis in rat testis.

This study aimed to investigate the effect of mono-(2-ethylhexyl) phthalate (MEHP), one of the major phthalate metabolites that are widespread in aquatic environments, on reproductive dysfunction, particularly on endocrine activity in adult male and female zebrafish. For 21 days, the zebrafish were exposed to test concentrations of MEHP (0, 2, 10, and 50 μg/mL) that were determined based on the effective concentrations (ECx) for zebrafish embryos. Exposure to 50 μg/mL MEHP in female zebrafish significantly decreased the number of ovulated eggs as well as the hepatic VTG mRNA abundance when those of the control group. Meanwhile, in female zebrafish, the biosynthetic concentrations of 17β-estradiol (E2) and the metabolic ratio of androgen to estrogen were remarkably increased in all MEHP exposed group compared with those in the control group, along with the elevated levels of cortisol. However, no significant difference was observed between these parameters in male zebrafishes. Therefore, exposure to MEHP causes reproductive dysfunction in female zebrafishes and this phenomenon can be attributed to the alteration in endocrine activities. Moreover, the reproductive dysfunction in MEHP-exposed female zebrafishes may be closely associated with stress responses, such as elevated cortisol levels. To further understand the effect of MEHP on the reproductive activities of fish, follow-up studies are required to determine the interactions between endocrine activities and stress responses. Overall, this study provides a response biomarker for assessing reproductive toxicity of endocrine disruptors that can serve as a methodological approach for an alternative to chronic toxicity testing.

Heavy metals have been found in increasing concentrations in the aquatic environment. Fishes exposed to such metals have altered gene expression, serum profiles, tissue histology and bioindices that serve as overall health biomarkers. The heavy metals (Ni, Cd, and Cr) accumulated in water and fish tissues, were beyond the permissible limits defined by the Central Pollution Control Board/World Health Organization. Metallothionein (MT) and glutathione peroxidase (GPX) genes expression patterns highlighted the metal-specific exposure of fish. An increased fold change of genes against beta-actin serves as a potential feature for toxicity. Metal toxicity is also reflected by an increased level of digestive enzymes (amylase and lipase) in the serum and alterations in values of reproductive hormones (11-Ketotestosterone and progesterone). Total serum bilirubin attribute to the liver and biliary tract disease in fishes. Histopathological studies show cellular degeneration, breakage, vacuolization signifying the chronic stress.

More attention was previously paid to adverse effects of steroids on aquatic organisms and their ecological risks to the aquatic environment. So far, little information has been reported on the bioaccumulative characteristics of different classes of steroids in cultured fish tissues. The present study for the first time provided a comprehensive analysis of the occurrence, bioaccumulation, and global consumers’ health risks via fish consumption of androgens, glucocorticoids and progestanges in typical freshwater cultured farms in South China. The numbers and total concentrations of steroids detected in the tissues of five common species of the cultured fish were in the order of plasma > bile > liver > muscle and plasma > bile, muscle > liver, respectively. The field bioaccumulation factors for the detected synthetic steroids ranged from 450 to 97,000 in bile, 450 to 65,000 in plasma, 2900 to 16,000 in liver, and 42 to 2600 in muscle of fish, respectively. This data suggests that steroids are bioaccumulative in fish tissues. Mostly important, 4-androstene-3,17-dione (AED) and cortisone (CRN) were found to be reliable chemical indicators to predict the levels of steroids in plasma and muscle of the inter-species cultured fish, respectively. Furthermore, the maximum hazard quotients (HQs) of testosterone and progesterone were 5.8 × 10−4 and 9.9 × 10−5, suggesting that human health risks were negligible via ingestion of the steroids-contaminated fish.

Benzo[a]pyrene (BaP) is a ubiquitous environmental persistent organic pollutant and a well-known endocrine disruptor. BaP exposure could alter the steroid balance in females. Endometrium decidualization and decidual angiogenesis are critical events for embryo implantation and pregnancy maintenance during early pregnancy and are modulated by steroids. However, the effect of BaP on decidualization is not clear. This study aimed to explore the effects of BaP on decidualization and decidual angiogenesis in pregnant mice. The result showed that the uteri in the BaP-treated groups were smaller and exhibited an uneven size compared with those in the control group. Artificial decidualization was detected in the uteri of the controls, but weakened decidualization response was observed in the BaP-treated groups. BaP significantly reduced the levels of estradiol, progesterone, and their cognate receptors ER and PR, respectively. The expression of several decidualization-related factors, including FOXO1, HoxA10, and BMP2, were altered after BaP treatment. BaP reduced the expression of cluster designation 34 (CD34), which indicated that the decidual angiogenesis was inhibited by BaP treatment. In addition, BaP induced the downregulation of vascular endothelial growth factor A. These data suggest that oral BaP ingestion compromised decidualization and decidual angiogenesis. Our results provide experimental data for the maternal reproductive toxicity of BaP during early pregnancy, which is very important for a comprehensive risk assessment of BaP on human reproductive health.

This work forwards new insights into the risk-assessment of multi-walled carbon-nanotubes (MWCNTs) while analysing the role of quantum-mechanical interactions between the electrons in the adsorption of probe compounds and biomolecules by MWCNTs. For this, the quantitative models are developed using quantum-chemical descriptors and their electron-correlation contribution. The major quantum-chemical factors contributing to the adsorption are found to be mean polarizability, electron-correlation energy, and electron-correlation contribution to the absolute electronegativity and LUMO energy. The proposed models, based on only three quantum-chemical factors, are found to be even more robust and predictive than the previously known five or four factors based linear free-energy and solvation-energy relationships. The proposed models are employed to predict the adsorption of biomolecules including steroid hormones and DNA bases. The steroid hormones are predicted to be strongly adsorbed by the MWCNTs, with the order: hydrocortisone > aldosterone > progesterone > ethinyl-oestradiol > testosterone > oestradiol, whereas the DNA bases are found to be relatively less adsorbed but follow the order as: guanine > adenine > thymine > cytosine > uracil. Besides these, the developed electron-correlation based models predict several insecticides, pesticides, herbicides, fungicides, plasticizers and antimicrobial agents in cosmetics, to be strongly adsorbed by the carbon-nanotubes. The present study proposes that the instantaneous inter-electronic interactions may be quite significant in various physico-chemical processes involving MWCNTs, and can be used as a reliable predictor for their risk assessment.

In this study we evaluate and demonstrate the occurrence of nine natural and one synthetic steroid hormone, including estrogens, androgens and progestagens in biogas final digestate byproduct (digestion liquid) commonly used as an agricultural fertilizer. We investigated two biogas sites that utilize different anaerobic digestion technologies (mesophilic and thermophilic) from swine manure and other organic wastes. Individual hormone concentration levels were observed up to 1478 ng g−1 dry weight or 22.5 mg kg−1 N with estrone and progesterone reaching highest concentration levels. Evaluation of the potential environmental burden through the application in agriculture was also assessed on the basis of predicted environmental concentrations. This study indicates that the biogas digestion process does not completely remove steroid hormones from livestock manure and use of final digestate byproduct on croplands contributes to the environmental emission of hormones.

Benzo [a]pyrene (BaP) is a well-known endocrine disruptor. Exposure to BaP is known to impair embryo implantation. The corpus luteum (CL), the primary source of progesterone during early pregnancy, plays a pivotal role in embryo implantation and pregnancy maintenance. The inappropriate luteal function may result in implantation failure and spontaneous abortions. However, the effect of BaP on CL remains unknown. This study investigated the deleterious effects of BaP on the structure and function of CL during early pregnancy. Pregnant rats were dosed with BaP at 0.2 mg.kg-1. d from day 1 (D1) to day 9 (D9) of gestation. We found that BaP reduced the number of CLs, disturbed the secretion of steroid and impacted the luteal vascular networks. BaP significantly decreased the angiogenesis factor (VEGFR, Ang-1 and Tie2) and increased the anti-angiogenic factor THBS1. Inhibited THBS1 function by LSKL partially rescued the angiogenesis defect caused by BaP. In vitro, BaP metabolite BPDE also interfered the expression levels of angiogenesis-related factors in HUVECs and impaired the angiogenesis, whereas supplemented with rAng-1 can alleviate the anti-angiogenic effect of BPDE. Furthermore, Notch signaling molecules, including Notch1, Dll4, Jag1 and Hey2, which are essential for the establishment and maturation of vascular networks, were affected by BaP exposure. Collectively, BaP broke the molecular regulatory balance between luteal angiogenesis and vascular maturation, impaired the construction of luteal vascular networks, and further affected luteal formation and endocrine function during early pregnancy. Our findings might provide new insight into the relationship between BaP and luteal insufficiency in early pregnancy. These data also give a new line of evidence for curtailing BaP emissions and protecting the women of childbearing age from occupational exposure.