Endocrine-disrupting chemicals (EDCs) are compounds that interfere with the expression, synthesis, and activity of hormones in organisms. They are released into the environment from flame retardants and products containing plasticizers. Persistent pesticides, such as dichlorodiphenyltrichloroethane (DDT) and hexachlorobenzene, also disrupt the endocrine system through interaction with hormone receptors. Endogenous hormones, such as 17β-estradiol (E2), are released in the urine and feces of farm animals and seep into terrestrial and aquatic ecosystems through sewage. Pigs are widely used as animal models to determine the effects of EDCs because they are physiologically, biochemically, and histologically similar to humans. EDCs primarily disrupt the reproductive and nervous systems of pigs. Moreover, embryonic development during the prenatal and early postnatal periods is particularly sensitive to EDCs. Mycotoxins, such as zearalenone, are food contaminants that alter hormonal activities in pigs. Mycotoxins also alter the innate immune system in pigs, making them vulnerable to diseases. It has been reported that farm animals are exposed to various types of EDCs, which accumulate in tissues, such as those of gonads, livers, and intestines. There is a lack of an integrated understanding of the impact of EDCs on porcine reproduction and development. Thus, this article aims to provide a comprehensive review of literature regarding the effects of EDCs in pigs.

The correlation between endocrine active contaminants in the environment and alterations in reproductive development of Sarotherodon melanotheron from Lagos lagoon has been investigated. Sediment and a total of 155 fish (74 males and 81 females) were collected between November 2014–March 2015 from selected contaminated sites (Ikorodu, Oworonshoki, Makoko and Idumota) and a putative control site (Igbore) along the lagoon. Sediment contaminant analysis revealed, significantly higher concentration of lindane, dieldrin, 4-iso-nonylphenol, 4-t-octylphenol and monobutyltin cation at the contaminated sites. Examination of gross morphological and histological changes of fish gonads showed a 27.4% prevalence of intersex in the sampled fish, of which 78% were males (testes-ova) and 22% were females (ovo-testis). Quantitative PCR (qPCR) of liver transcripts revealed the presence of vitellogenin (vtg) levels in male fish from contaminated sites. Zona radiata proteins (zrp) mRNA levels were significantly higher in females, compared to male fish. In general, significantly lower vtg and zrp transcripts levels were recorded at Igbore (control site), compared with contaminated sites. Principal component analysis (PCA) showed site and sex relationship in biological responses and contaminants, including trace metals, demonstrating that measured endocrine responses in fish were associated with contaminant burden in sediment. In addition, positive relationships were observed in male fish from Idumota, Oworonshoki and Ikorodu with vtg and dieldrin/4-iso-nonyphenol, with higher levels in male fish, compared to females. Further, contaminants from the Makoko, Oworonshoki and Ikorodu sites were positively associated with higher GSI and zrp in females. More importantly, the severity of intersex and changes in vtg transcripts imply a progressive feminization of male fish with concomitant alteration in the reproductive health of fish inhabiting the Lagos lagoon.

Nitrate is a ubiquitous aquatic pollutant that is commonly associated with eutrophication and dead zones in estuaries around the world. At high concentrations nitrate is toxic to aquatic life but at environmental concentrations it has also been purported as an endocrine disruptor in fish. To investigate the potential for nitrate to cause endocrine disruption in fish, we conducted a lifecycle study with fathead minnows (Pimephales promelas) exposed to nitrate (0, 11.3, and 56.5 mg/L (total nitrate-nitrogen (NO3-N)) from <24 h post hatch to sexual maturity (209 days). Body mass, condition factor, gonadal somatic index (GSI), incidence of intersex, and vitellogenin induction were determined in mature male and female fish and plasma 11-keto testosterone (11-KT) was measured in males only. In nitrate-exposed males both 11-KT and vitellogenin were significantly induced when compared with controls. No significant differences occurred for body mass, condition factor, or GSI among males and intersex was not observed in any of the nitrate treatments. Nitrate-exposed females also had significant increases in vitellogenin compared to controls but no significant differences for mass, condition factor, or GSI were observed in nitrate exposed groups. Estradiol was used as a positive control for vitellogenin induction. Our findings suggest that environmentally relevant nitrate levels may disrupt steroid hormone synthesis and/or metabolism in male and female fish and may have implications for fish reproduction, watershed management, and regulation of nutrient pollution.

People living a subsistence lifestyle in the Arctic are highly exposed to persistent organic pollutants, including polychlorinated biphenyls (PCBs). Formerly Used Defense (FUD) sites are point sources of PCB pollution; the Arctic contains thousands of FUD sites, many co-located with indigenous villages. We investigated PCB profiles and biological effects in freshwater fish (Alaska blackfish [Dallia pectoralis] and ninespine stickleback [Pungitius pungitius]) living upstream and downstream of the Northeast Cape FUD site on St. Lawrence Island in the Bering Sea. Despite extensive site remediation, fish remained contaminated with PCBs. Vitellogenin concentrations in males indicated exposure to estrogenic contaminants, and some fish were hypothyroid. Downstream fish showed altered DNA methylation in gonads and altered gene expression related to DNA replication, response to DNA damage, and cell signaling. This study demonstrates that, even after site remediation, contaminants from Cold War FUD sites in remote regions of the Arctic remain a potential health threat to local residents – in this case, Yupik people who had no influence over site selection and use by the United States military.

Interactions between organic toxicants and nano-particles in the aquatic environment may modify toxicant bioavailability and consequently the toxicant's fate and toxicity. To evaluate the potential impact of nano-titanium dioxide (TiO₂) on the bio-concentration and reproductive endocrine disruption of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) in fish, a comparative bioaccumulation study was conducted on zebrafish (Danio rerio, AB strain) treated with 0, 5.74, 23.6, or 90.7 μg L⁻¹ TDCIPP alone or co-exposed to TDCIPP and 0.09 mg L⁻¹ nano-TiO₂ for 21 days. Nano-TiO₂ can absorb TDCIPP and nano-TiO₂ is taken up into zebrafish. Chemical measurements showed that TDCIPP was bio-concentrated in zebrafish, and the highest level was detected in the liver, followed by the brain and gonads. Compared with TDCIPP treatment, increased tissue burdens of both TDCIPP were observed in the liver, brain, and gonads suggesting that nano-TiO₂ adsorbed TDCIPP and acted as a carrier facilitating the uptake and translocation of TDCIPP in tissues. Higher bio-concentration in the presence of nano-TiO₂ resulted in a significant decrease in the hepatic-somatic index, gonad-somatic index and brain-somatic index in F0 females but not F0 males. Moreover, a further gender-dependent reduction in testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and induction of plasma vitellogenin (VTG) concentrations in adults were observed following co-exposure. Co-exposure also inhibited egg production and caused significant developmental toxicity in F1 larvae. The results obtained using this multi-marker approach suggested that nano-TiO₂ is a carrier of TDCIPP and accelerated its bio-concentration in adult zebrafish, resulting in adverse reproduction outcomes.

The concentrations, distributions, and bioaccumulation of nine organophosphate flame retardants (OPFRs) were investigated in both abiotic and biotic media, comprising river water, sediment, and crucian carp. The highest concentrations were observed in liver (6.22–18.1 ng/g ww), and the levels in muscle (4.23–7.75 ng/g ww) and gonad (3.08–7.70 ng/g ww) were similar. In whole blood, tris(2-butoxyethyl) phosphate (TBOEP; 31.1–256 ng/mL) accounted for 90% of the total OPFR concentration. Distributions of OPFRs differed between biotic and abiotic media, as tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCIPP), and TBOEP were dominant in abiotic media, whereas triethyl phosphate (TEP), tri-n-butyl phosphate (TNBP), TCEP, and TBOEP dominated in crucian carp. The TNBP had remarkable accumulation potential among nine OPFRs, which the TNBP concentrations in muscle increased with increased total length and body weight. The higher perfusion rate of TNBP to female eggs were observed rather than to male gonads as the concentrations were higher in males than in females, while the opposite results were observed in gonad. Moreover, the concentration of TNBP in female muscle began to decrease near maximum growth as a sexually dimorphic difference in crucian carp. This is the first study to simultaneously investigate the fate of OPFRs in biotic and abiotic media and to show sex differences.

Due to their terrestrial habitats and aquatic reproduction, many amphibians are both very vulnerable and highly suitable bioindicators. The plasticizer bisphenol A (BPA) is one of the most produced chemical substances worldwide, and knowledge on its impacts on humans and animals is mounting. BPA is used for the industrial production of polycarbonate plastics and epoxy resins and found in a multitude of consumer products. Studies on BPA have involved mammals, fish and the fully aquatic anuran model Xenopus laevis. However, our knowledge about the sexual development of non-model, often semi-terrestrial anuran amphibians remains poor. Using a recently developed experimental design, we simultaneously applied BPA to two non-model species (Hyla arborea, Hylidae; Bufo viridis, Bufonidae) and the model X. laevis (Pipidae), compared their genetic and phenotypic sex for detection of sex reversals, and studied sexual development, focusing on anatomical and histological features of gonads. We compared three concentrations of BPA (0.023, 2.28 and 228 μg/L) to control groups in a high-standard flow-through-system, and tested whether conclusions, drawn from the model species, can be extrapolated to non-model anurans. In contrast to previous studies on fish and Xenopus, often involving dosages much higher than most environmental pollution data, we show that BPA causes neither the development of mixed sex nor of sex-reversed individuals (few, seemingly BPA-independent sex reversals) in all focal species. However, environmentally relevant concentrations, as low as 0.023 μg/L, were sufficient to provoke species-specific anatomically and histologically detectable impairments of gonads, and affected morphological traits of metamorphs. As the intensity of these effects differed between the three species, our data imply that BPA diversely affects amphibians with different evolutionary history, sex determination systems and larval ecologies. These results highlight the role of amphibians as a sensitive group that is responsive to environmental pollution.

Metals and metalloids are natural components of the biosphere, which are not produced per se by human beings, but whose form and distribution can be affected by human activities. Like all substances, they are a contaminant if present in excess compared to background levels and/or in a form that would not normally occur in the environment. Samples of liver, gills, gonads and muscle from European chub, Squalius cephalus, were analyzed for Al, As, B, Ba, Cr, Cu, Fe, Hg, Mn, Mo, Sr and Zn using inductively coupled plasma optical emission spectrometry (ICP-OES) to highlight the importance of tissue selection in monitoring research. The comet assay or single cell gel electrophoresis (SCGE) was selected as an in vivo genotoxicity assay, a rapid and sensitive method for measuring genotoxic effects in blood, liver and gills of the European chub. Microscopic images of comets were scored using Comet IV Computer Software (Perceptive Instruments, UK).The objective of our study was to investigate two reservoirs, Zlatar and Garasi, and one river, Pestan by: (i) determining and comparing metal and metalloid concentrations in sediment, water and tissues of European chub: liver, gills, muscle and gonads (ii) comparing these findings with genotoxicity of water expressed through DNA damage of fish tissues.A clear link between the level of metals in water, sediment and tissues and between metal and genotoxicity levels at examined sites was not found. This suggests that other xenobiotics (possibly the organic compounds), contribute to DNA damage.

Perfluorooctanesulphonic acid (PFOS) is a ubiquitous contaminant in the aquatic environment and our earlier studies demonstrated that chronic PFOS exposures lead to a female-biased sex ratio and decreased sperm quality in male zebrafish. The underlying mechanism for these reproductive effects is unknown. In the present study, 8 h post-fertilization (hpf) zebrafish were exposed to PFOS at 250 μg/L for 5 months, and the levels of sex hormones, expression of sex determination related genes, and histological and ultrastructural changes of gonads were fully characterized. During the sex differentiation period, we observed elevated estradiol (E2) and decreased testosterone (T) levels in whole tissue homogenates from PFOS exposed juveniles. In fully mature adult male fish, serum E2 levels were slightly increased, however, the estrogen receptor alpha (esr1) was significantly elevated in PFOS treated male gonads. Histological and electron microscopic examinations revealed structural changes in the gonads of PFOS exposed male and female adult zebrafish. In summary, chronic PFOS exposure disrupts sex hormone level and related gene expression and impairs gonadal development, which may contribute to the previously reported PFOS reproductive toxicity.

Drospirenone (DRO) is one of the most widely used progestins in contraceptive treatments and hormone replacement therapies. The pharmacokinetics and potential toxicological effects of DRO were investigated in juvenile sea bass (Dicentrarchus labrax) exposed through the diet (0.01–10 μg DRO/g) for up to 31 days. DRO was detected in the blood (4–27 ng/mL) of fish exposed to the highest concentration, with no significant bioaccumulation over time and no alteration of hepatic metabolizing enzymes, namely, CYP1A and CYP3A-catalysed activities and UDP-glucuronyltransferase (UGT). Pregnenolone (P5), progesterone (P4), 17α-hydroxyprogesterone (17P4), 17α-hydroxypregnenolone (17P5), androstenedione (AD) and testosterone (T) were determined in plasma and gene expression of cyp17a1, cyp19a1a and cyp11β analysed by qRT-PCR in gonads. The significant increase in plasmatic levels of 17P5, 17P4 and AD detected after 31 days exposure to 10 ng DRO/g together with the increased expression of cyp17a1 in females evidence the ability of DRO to alter steroid synthesis at low intake concentrations (7 ng DRO/day). However, the potential consequences of this steroid shift for female reproduction remain to be investigated.