South Africa is the largest agrochemical user in sub-Saharan Africa, with over 3000 registered pesticide products. Although they reduce crop losses, these chemicals reach non-target aquatic environments via leaching, spray drift or run-off. In this review, attention is paid to legacy and current-use pesticides reported in literature for the freshwater environment of South Africa and to the extent these are linked to endocrine disruption. Although banned, residues of many legacy organochlorine pesticides (endosulfan and dichlorodiphenyltrichloroethane (DDT)) are still detected in South African watercourses and wildlife. Several current-use pesticides (triazine herbicides, glyphosate-based herbicides, 2,4-dichlorophenoxyacetic acid (2,4-D) and chlorpyrifos) have also been reported. Agrochemicals can interfere with normal hormone function of non-target organism leading to various endocrine disrupting (ED) effects: intersex, reduced spermatogenesis, asymmetric urogenital papillae, testicular lesions and infertile eggs. Although studies investigating the occurrence of agrochemicals and/or ED effects in freshwater aquatic environments in South Africa have increased, few studies determined both the levels of agricultural pesticides present and associated ED effects. The majority of studies conducted are either laboratory-based employing in vitro or in vivo bioassays to determine ED effects of agrochemicals or studies that investigate environmental concentrations of pesticides. However, a combined approach of bioassays and chemical screening will provide a more comprehensive overview of agrochemical pollution of water systems in South Africa and the risks associated with long-term chronic exposure.

Tris (2-ethylhexyl) phosphate (TEHP) is one of the most commonly used organophosphorus flame retardant (OPFR) analogues and is commonly detected in surface water and sediments. Limited information is available about the metabolic pathway or metabolite formation related to TEHP in fish. In this study, rare minnows (Gobiocyprisrarus) were exposed to TEHP in static water for 30 d to investigate the bioaccumulation and metabolite distribution in the fish muscle, liver, kidney, gill, GI-tract, ovary and testis. Based on the estimated kᵤₚ,ₚₐᵣₑₙₜ and kd,ₚₐᵣₑₙₜ values, the bioconcentration factors (BCFₚₐᵣₑₙₜ) of TEHP in fish tissues were calculated in the order of kidney > ovary ≈ liver ≈ testis > gill ≈ GI-tract > muscle; this finding was consistent with the results of our previous study on other alkyl-substituted OPFRs. In addition, this study identified the metabolic profiles of TEHP in the liver. TEHP was oxidatively metabolized by the fish to a dealkylated metabolite (di 2-ethylhexyl phosphate; DEHP) and hydroxylated TEHP (OH-TEHP). OH-TEHP further underwent extensive phase II metabolism to yield glucuronic acid conjugates. DEHP was mainly distributed in rare minnow in the following order: liver > GI-tract > kidney ≫ other tissues. However, the metabolite showed lower accumulation potential in fish tissues than TEHP, with metabolite parent concentration factors (MPCFs) for DEHP of less than 0.1 in all the investigated tissues. The BCFₚₐᵣₑₙₜ values of TEHP in various fish tissues were only 9.0 × 10⁻³-7.2 × 10⁻⁴ times its estimated tissue-water partition coefficient (Kₜᵢₛₛᵤₑ₋wₐₜₑᵣ) values based on tissue lipid, protein and water contents, which indicated the significance of biotransformation in reducing the bioaccumulation potential of TEHP in fish. The toxicokinetic data in the present study help in understanding the tissue-specific bioaccumulation and metabolism pathways of TEHP in fish and highlight the importance of toxicology research on TEHP metabolites in aquatic organisms.

There is little information about the residue levels and congener composition of organic contaminants (OCs) in cetaceans. In the present study, we investigated the polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs) in the blubber, blood, brain and testes of Indo-Pacific humpback dolphins (Sousa chinensis) stranded in the Pearl River Estuary (PRE), China. The lowest blubber/tissue partition coefficients were found for sum hexachlorocyclohexanes (ΣHCHs) and ΣPAHs, while the highest were in ΣPCBs and sum dichlorodiphenyltrichloroethanes (ΣDDTs), likely attributing to the octanol-water partition features. The low levels of OCs in brain and testes theoretically resulted from the blood-brain barrier, blood-testes barrier, contaminant molecule dimensions and unique lipid compositions in the brain and testes. Compared with other contaminants, the higher mean brain/blood and testes/blood partition coefficients found for mirex, heptachlor, dieldrin and endrin would increase the risks associated with exposure-related toxicity and the bioavailability of contaminants within these tissues. Observations also suggest that as lipid mobilizes from blubber, contaminants may redistribute, leading to elevated tissue (such as brain) concentrations. Therefore, dolphins with less blubber may be more susceptible to health risks. The Indo-Pacific humpback dolphins living in PRE are at great risk due to variety of OCs in indirect contact with non-target organisms, affecting the health of animals (toxic effects and accumulation). Our findings contribute to the knowledge of the potential effects of OCs exposure on developmental neurotoxicity and reproductive damage in marine mammals.

Organophosphate flame retardants (OPFRs) are widespread in the aquatic environment, but the effects of these chemicals on reproductive toxicity are far from clear. In this study, sperm quality in adult male Chinese rare minnows after exposure to tris-(2-butoxyethyl) phosphate (TBOEP), tris-(1,3-dichloro-2-propyl) phosphate (TDCIPP), and triphenyl phosphate (TPHP) was investigated. No obvious change in sperm concentration and vitality was observed after treatments, whereas significant changes in sperm velocity and morphology were found following all treatments (P < 0.05). Moreover, OPFR exposure significantly increased the apoptosis ratios in testis cells. Analysis of the transcriptomic data revealed that Na⁺/K⁺ ATPase (NKA) related genes were significantly downregulated, and the NKA enzyme activities after all treatments were significantly inhibited (P < 0.05). However, no obvious change in hormone levels in the groups exposed to TBOEP and TDCIPP was observed. These findings indicate that the OPFR-induced reduction of sperm quality might be due to the effects of OPFRs on NKA enzyme instead of changes in hormone levels.

Tetrabromobisphenol-A (TBBPA) is an emerging organic pollutant and a commonly used brominated flame retardant that has received much attention owing to its toxicity. Although TBBPA is ubiquitously detected in atmospheric particulate matter and dust, few studies have investigated the sub-chronic inhalation exposure to TBBPA. To further understand the excretion characteristics and tissue accumulation of TBBPA after inhalation exposure, we used the rat model to conduct a sub-chronic inhalation exposure study. Male rats were administered with different doses of aerosol TBBPA (12.9, 54.6, 121.6, and 455.0 mg/m³). TBBPA was found in the excretion (feces and urine) and all the target tissues (lung, liver, heart, thymus gland, spleen, testicles, muscles, kidneys, brain and serum). Feces were the main route of excretion, which contributed 19.18% to 72.54% (urine <0.10%). TBBPA excretion through feces following inhalation administration was much higher than that following oral and dermal exposure, thereby indicating lower bioavailability of TBBPA under inhalation exposure. Liver and serum showed higher levels of TBBPA compared with those of other tissues, thereby suggesting tissue-specific accumulation of TBBPA in rats. Owing to the relative non-invasiveness of serum sampling and greatest TBBPA concentration among the tissues, serum is a suitable matrix for estimation of TBBPA bioaccumulation after inhalation exposure.

The growing use of octocrylene (OC) in sunscreens has posed a great threat to aquatic organisms. In the present study, to assess its reproductive toxicity and mechanism, paired Japanese medaka (Oryzias latipes) (F0) were exposed to OC at nominal concentrations of 5, 50, and 500 μg/L for 28 d. Significant increases were observed in the gonadosomatic index (GSI) and hepatosomatic index (HSI) of F0 medaka at 500 μg/L OC (p < 0.05) without significant differences in fecundity. The fertility was significantly decreased at all treatments (p < 0.05). Significant increases in the percent of mature oocytes were observed at 5 and 500 μg/L OC, in which contrary to the percent of spermatozoa (p < 0.05). The plasma sex hormones and vitellogenin levels significantly increased in males at all treatments and in females at 50 and 500 μg/L OC (p < 0.05). In addition, the levels of fshβ and lhβ in the brains and the levels of fshr, lhr and cyp17α in the gonads were significantly upregulated in males at all treatments (p < 0.05), in line with those of ar, erα, erβ and cyp19β in the brains of male and female. The upregulation of vtg in male and female livers was observed only at 500 μg/L OC and upregulation of star and hsd3β was observed in testis at all treatments (p < 0.05). Continued exposure to OC significantly induced increases in the time to hatching, morphological abnormality rates, and cumulative death rates of F1 embryos, inconsistent with body length of F1 larvae (p < 0.05). Therefore, the responses of the exposed fish at the biochemical and molecular levels indicated reproductive toxicity and estrogenic activity of OC, providing insights into the mechanism of OC.

Controversial glyphosate-based herbicides (GBHs) are the most frequently used herbicides globally. GBH residues in the wild, in animal and human food may expose non-target organisms to health risks, yet the developmental and cumulative effects of GBHs on physiology and reproduction remain poorly understood. We present the first long-term study on the effects of subtoxic GBH exposure (160 mg/kg) on multiple key physiological biomarkers (cellular oxidative status and neurotransmitters), gut microbiome, reproductive hormones, and reproduction in an avian model. We experimentally exposed in Japanese quail females and males (Coturnix japonica) to GBHs and respective controls from the age of 10 days–52 weeks. GBH exposure decreased hepatic activity of an intracellular antioxidant enzyme (catalase), independent of sex, but did not influence other intracellular oxidative stress biomarkers or neurotransmitter enzyme (acetylcholinesterase). GBH exposure altered overall gut microbiome composition, especially at a younger age and in females, and suppressed potentially beneficial microbes at an early age. Many of the microbial groups increased in frequency from 12 to 28 weeks under GBH exposure. GBH exposure decreased male testosterone levels both at sexual maturity and at 52 weeks of exposure, but did not clearly influence reproduction in either sex (maturation, testis size or egg production). Future studies are needed to characterize the effects on reproductive physiology in more detail. Our results suggest that cumulative GBH exposure may influence health and reproduction-related traits, which is important in predicting their effects on wild populations and global poultry industry.

Metal pollution has been associated with anthropogenic activities, such as effluents and emissions from mines. Soil could be exposure route of wild rats to metals, especially in mining areas. The aim of this study was to verify whether soil exposure under environmentally relevant circumstances results in metal accumulation and epigenetic modifications. Wistar rats were divided to three groups: 1) control without soil exposure, 2) low-metal exposure group exposed to soil containing low metal levels (Pb: 75 mg/kg; Cd: 0.4), and 3) high-metal exposure group exposed to soil (Pb: 3750; Cd: 6). After 1 year of exposure, the metal levels, Pb isotopic values, and molecular indicators were measured. Rats in the high-group showed significantly greater concentrations of Pb and Cd in tissues. Higher accumulation factors (tissue/soil) of Cd than Pb were observed in the liver, kidney, brain, and lung, while the factor of Pb was higher in the tibia. The obtained results of metal accumulation ratios (lung/liver) and stable Pb isotope ratios in the tissues indicated that the respiratory exposure would account for an important share of metal absorption into the body. Genome-wide methylation status and DNA methyltransferase (Dnmt 3a/3b) mRNA expressions in testis were higher in the high-group, suggesting that exposure to soil caused metal accumulation and epigenetic alterations in rats.

T-2 toxin is an unavoidable contaminant in human food, animal feeds, and agricultural products. T-2 toxin has been found to impair male reproductive function. But, few data is available that reveals the reproductive toxicity mechanism. In the study, male Kunming mice were orally administrated with T-2 toxin at the doses of 0, 0.5, 1 or 2 mg/kg body weight for 28 days. The body and reproductive organs weight, the concentration, malformation rate and ultrastructure of sperm in cauda epididymis were detected. Oxidative stress biomarkers and apoptosis were also measured in testes. Histological change of testes was performed by H&E and TUNEL staining. T-2 toxin down-regulated body and reproductive organs (testis, epididymis and seminal vesicle) weight, sperm concentration, increased sperm malformation rate and damaged the ultrastructure of sperm and structure of testes. T-2 toxin treatment increased the reactive oxygen species (ROS) and malondialdehyde content, while, decreased the total anti-oxidation capacity (T-AOC) and the superoxide dismutase activity in testes. T-2 toxin exposure increased the TUNEL-positive germ cells, the activities and mRNA expressions of caspase-3, caspase-8 and caspase-9, the mRNA expression of Bax, and inhibited the Bcl-2 mRNA expression. Furthermore, the expressions of caspase-3, caspase-8 caspase-9 and Bax were positively correlated with ROS level, but negatively correlated with T-AOC in testis. In summary, T-2 toxin caused spermatogenesis disorder associated with the germ cell apoptosis medicated by oxidative stress, impairing the male reproductive function.

The effect of fluoride as an ongoing topic has attracted much attentions due to the decline in overall human fertility worldwide. However, whether fluorine causes a temporary stimulus or permanent damage to the male reproductive system, as well as the mechanism of fluoride influencing spermatogenesis remained unclear. 48 adult male rats were randomly divided into four groups (twelve each). Control group received the distilled water, while the other three groups were treated with 25, 50, 100 mg/L NaF via drinking water for 8 weeks. Six rats from each group were selected randomly to detect the levels of various indices related to spermatogenesis. The remaining rats were given only distilled water and left for recovery of a period of 2 weeks. Results showed that the levels of serum CK, ALP, CHE, BUN, UA, and Cr, testis morphology and the ultrastructure of sperm acrosome and chromatoid body (CB) were significantly changed by fluoride. Interestingly, the elongated spermatid counts, spermatids elongation ratio, and mRNA expressions of Prm1/2 and MIWI, TDRD1, TDRD 6, TDRD7, PABP, and Hsp72 related to CB decreased markedly in fluoride treatment groups compared to the control. Furthermore, the expression levels of DDX25 and associated regulatory proteins like CRM1, HMG2, H4, TP2, and PGK2 were down-regulated by fluoride. After 2-weeks withdrawal period, out of the 19 altered spermatogenesis indicators, 15 indicators in 100 mg/L group and 3 indicators in 50 mg/L group still exhibited a significant change, while none showed change in 25 mg/L group. These results proved that the reversibility of fluoride toxicity is dose-dependent on the male reproductive system. Meanwhile, fluoride caused unrestored arrest during the haploid period of spermatogenesis, where reduced DDX25 and associated regulatory proteins play a crucial role in this process, which could provide the underlying insights to the toxic mechanism of fluoride induced male reproductive toxicity.