Toward invasive mussel genetic biocontrol: Approaches, challenges, and perspectives.

Invasive freshwater mussels, such as the zebra (Dreissena polymorpha), quagga (Dreissena rostriformis bugensis), and golden (Limnoperna fortunei) mussel have spread outside their native ranges throughout many regions of the North American, South American, and European continents in recent decades, damaging infrastructure and the environment. This review describes ongoing efforts by multiple groups to develop genetic biocontrol methods for invasive mussels. First, we provide an overview of genetic biocontrol strategies that have been applied in other invasive or pest species. Next, we summarize physical and chemical methods that are currently in use for invasive mussel control. We then describe the multidisciplinary approaches our groups are employing to develop genetic biocontrol tools for invasive mussels. Finally, we discuss the challenges and limitations of applying genetic biocontrol tools to invasive mussels. Collectively, we aim to openly share information and combine expertise to develop practical tools to enable the management of invasive freshwater mussels.

Effects of Nitrate and Conductivity on Embryo-Larval Fathead Minnows.

Nitrate concentrations have been rising in surface waters over the last century and now frequently exceed drinking water standards and environmental safety benchmarks globally. Health-wise, these trends are concerning because nitrate has been shown to disrupt endocrine function and developmental outcomes. The present study investigated potential sublethal effects of nitrate on developing fathead minnows. Fish were exposed from fertilization through 21 days postfertilization (dpf) to environmentally relevant concentrations of nitrate (0, 2, 5, 10, 25, or 100 mg/L NO3 -N as NaNO3 ). Nitrate effects on hatch timing, heart rate and rhythm at 3 dpf, growth through 21 dpf, swim bladder inflation timing and size, scoliosis, pericardial edema, and mortality were assessed. Because adding NaNO3 increases water conductivity, two conductivity controls were included to match the ionic strength of the 10- and 100-mg/L NO3 -N treatments. Increasing nitrate delayed posterior swim bladder (PSB) inflation in a dose-dependent manner, with possible inhibition of anterior swim bladder (ASB) inflation at higher doses, although nitrate did not affect swim bladder size. Conversely, nitrate did not affect hatch timing or cardiac endpoints at 3 dpf or induce pericardial edema or scoliosis, although there was a noted brood effect on these latter defects. As was observed with increasing nitrate, higher ion concentrations in the conductivity controls caused dose-dependent increases in fish body size at 21 dpf. Increased ionic strength also hastened ASB inflation independently of nitrate. As in other published studies, the observed delay in PSB inflation suggests that nitrate disrupts the thyroid axis and warrants further investigation. In addition, the present study supports the need for conductivity controls in nitrate toxicity studies to distinguish nitrate-specific effects. Environ Toxicol Chem 2023;42:1529-1541. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.

Widespread Use of the Nitrification Inhibitor Nitrapyrin: Assessing Benefits and Costs to Agriculture, Ecosystems, and Environmental Health.

Agricultural production and associated applications of nitrogen (N) fertilizers have increased dramatically in the last century, and current projections to 2050 show that demands will continue to increase as the human population grows. Applied in both organic and inorganic fertilizer forms, N is an essential nutrient in crop productivity. Increased fertilizer applications, however, create the potential for more N loss before plant uptake. One strategy for minimizing N loss is the use of enhanced efficiency fertilizers, fortified with a nitrification inhibitor, such as nitrapyrin. In soils and water, nitrapyrin inhibits the activity of ammonia monooxygenase, a microbial enzyme that catalyzes the first step of nitrification from ammonium to nitrite. Potential benefits of using nitrification inhibitors range from reduced nitrate leaching and nitrous oxide emissions to increased crop yield. The extent of these benefits, however, depends on environmental conditions and management practices. Thus, such benefits are not always realized. Additionally, nitrapyrin has been shown to transport off-field, and it is unknown what effects environmental nitrapyrin could have on nontarget organisms and the ecological nitrogen cycle. Here, we review the agronomic and environmental benefits and costs of nitrapyrin use and present a series of research questions and considerations to be addressed with future nitrification inhibitor research.

Low oxygen: A (tough) way of life for Okavango fishes.

Botswana's Okavango Delta is a World Heritage Site and biodiverse wilderness. In 2016-2018, following arrival of the annual flood of rainwater from Angola's highlands, and using continuous oxygen logging, we documented profound aquatic hypoxia that persisted for 3.5 to 5 months in the river channel. Within these periods, dissolved oxygen rarely exceeded 3 mg/L and dropped below 0.5 mg/L for up to two weeks at a time. Although these dissolved oxygen levels are low enough to qualify parts of the Delta as a dead zone, the region is a biodiversity hotspot, raising the question of how fish survive. In association with the hypoxia, histological samples, collected from native Oreochromis andersonii (threespot tilapia), Coptodon rendalli (redbreast tilapia), and Oreochromis macrochir (greenhead tilapia), exhibited widespread hepatic and splenic inflammation with marked granulocyte infiltration, melanomacrophage aggregates, and ceroid and hemosiderin accumulations. It is likely that direct tissue hypoxia and polycythemia-related iron deposition caused this pathology. We propose that Okavango cichlids respond to extended natural hypoxia by increasing erythrocyte production, but with significant health costs. Our findings highlight seasonal hypoxia as an important recurring stressor, which may limit fishery resilience in the Okavango as concurrent human impacts rise. Moreover, they illustrate how fish might respond to hypoxia elsewhere in the world, where dead zones are becoming more common.

Prevalence of Eight Phthalate Monoesters in Water from the Okavango Delta, Northern Botswana.

Phthalate diesters are used in personal care products, plastics, and pesticides, resulting in widespread human and wildlife exposure. Phthalate diesters leach out of these products and ultimately enter biological systems where they are quickly metabolized to phthalate monoesters and glucuronides. As such, phthalate monoesters can serve as indicators of anthropogenic activity in wilderness areas. The Okavango Delta, an inland seasonal wetland covering 5000-12,000 km2 in Botswana, provides fresh water to many species of birds, fish, reptiles, and large mammals. Water samples (N = 46) were taken from across the Okavango water system, extracted, and analyzed for eight different phthalate monoesters using liquid chromatography and isotope dilution mass spectrometry. Seven of eight phthalate monoesters were detected from the low ng/L to low µg/L levels. Phthalate monoesters were found in samples from all five sampling regions. Sources of these contaminants are unknown, but their presence indicates encroachment of human activity on the Okavango Delta.

Reproductive endocrinology of environmental nitrate.

Nitrate is a widespread contaminant of aquatic ecosystems and drinking water. It is also broadly active in organismal physiology, and as such, has the potential to both enhance and disrupt normal physiological function. In animals, nitrate is a proposed endocrine disrupter that is converted in vivo to nitrite and nitric oxide. Nitric oxide, in particular, is a potent cell signaling molecule that participates in diverse biological pathways and events. Here, we review in vivo nitrate cycling and downstream mechanistic physiology, with an emphasis on reproductive outcomes. However, in many cases, the research produces contradictory results, in part because there is good evidence that nitrate follows a non-monotonic dose-response curve. This conundrum highlights an array of opportunities for scientists from different fields to collaborate for a full understanding of nitrate physiology. Opposing conclusions are especially likely when in vivo/in vitro, long term/short term, high dose/low dose, or hypoxia/normoxia studies are compared. We conclude that in vivo studies are most appropriate for testing an organism's integrated endocrine response to nitrate. Based on the limited available studies, there is a generalized trend that shorter term studies (less than 1 month) or studies involving low doses (≤5 mg/L NO3-N) cause steroid hormone levels to decline. Studies that last more than a month and/or involve higher, but still environmentally relevant, exposures (>50-100 mg/L NO3-N) cause steroid hormone levels to increase. Very high nitrate doses (>500 mg/L NO3-N) are cytotoxic in many species. Hypoxia and acidity are likely to intensify the effects of nitrate. For study design, degree of study animal reproductive maturity or activity is important, with immature/reproductively quiescent animals responding to nitrate differently, compared with reproductively active animals. A detailed table of studies is presented.

Detecting Estrogenic Ligands in Personal Care Products using a Yeast Estrogen Screen Optimized for the Undergraduate Teaching Laboratory.

The Yeast Estrogen Screen (YES) is used to detect estrogenic ligands in environmental samples and has been broadly applied in studies of endocrine disruption. Estrogenic ligands include both natural and manmade "Environmental Estrogens" (EEs) found in many consumer goods including Personal Care Products (PCPs), plastics, pesticides, and foods. EEs disrupt hormone signaling in humans and other animals, potentially reducing fertility and increasing disease risk. Despite the importance of EEs and other Endocrine Disrupting Chemicals (EDCs) to public health, endocrine disruption is not typically included in undergraduate curricula. This shortcoming is partly due to a lack of relevant laboratory activities that illustrate the principles involved while also being accessible to undergraduate students. This article presents an optimized YES for quantifying ligands in personal care products that bind estrogen receptors alpha (ERα) and/or beta (ERß). The method incorporates one of the two colorimetric substrates (ortho-nitrophenyl-ß-D-galactopyranoside (ONPG) or chlorophenol red-ß-D-galactopyranoside (CPRG)) that are cleaved by ß-galactosidase, a 6-day refrigerated incubation step to facilitate use in undergraduate laboratory courses, an automated application for LacZ calculations, and R code for the associated 4-parameter logistic regression analysis. The protocol has been designed to allow undergraduate students to develop and conduct experiments in which they screen products of their choosing for estrogen mimics. In the process, they learn about endocrine disruption, cell culture, receptor binding, enzyme activity, genetic engineering, statistics, and experimental design. Simultaneously, they also practice fundamental and broadly applicable laboratory skills, such as: calculating concentrations; making solutions; demonstrating sterile technique; serially diluting standards; constructing and interpolating standard curves; identifying variables and controls; collecting, organizing, and analyzing data; constructing and interpreting graphs; and using common laboratory equipment such as micropipettors and spectrophotometers. Thus, implementing this assay encourages students to engage in inquiry-based learning while exploring emerging issues in environmental science and health.

Nitrate induces a type 1 diabetic profile in alligator hatchlings.

Type 1 diabetes (T1D) is a chronic autoimmune disease that affects 1 in 300 children by age 18. T1D is caused by inflammation-induced loss of insulin-producing pancreatic beta cells, leading to high blood glucose and a host of downstream complications. Although multiple genes are associated with T1D risk, only 5% of genetically susceptible individuals actually develop clinical disease. Moreover, a growing number of T1D cases occur in geographic clusters and among children with low risk genotypes. These observations suggest that environmental factors contribute to T1D etiology. One potential factor, supported primarily by epidemiological studies, is the presence of nitrate and nitrite in drinking water. To test this hypothesis, female hatchling alligators were exposed to environmentally relevant concentrations of nitrate in their tank water (reference, 10mg/L, or 100mg/L NO3-N) from hatch through 5 weeks or 5 months of age. At each time point, endpoints related to T1D were investigated: plasma levels of glucose, triglycerides, testosterone, estradiol, and thyroxine; pancreas, fat body, and thyroid weights; weight gain or loss; presence of immune cells in the pancreas; and pancreatic beta cell number, assessed by antibody staining of nkx6.1 protein. Internal dosing of nitrate was confirmed by measuring plasma and urine nitrate levels and whole blood methemoglobin. Cluster analysis indicated that high nitrate exposure (most animals exposed to 100mg/L NO3-N and one alligator exposed to 10mg/L NO3-N) induced a profile of endpoints consistent with early T1D that could be detected after 5 weeks and was more strongly present after 5 months. Our study supports epidemiological data correlating elevated nitrate with T1D onset in humans, and highlights nitrate as a possible environmental contributor to the etiology of T1D, possibly through its role as a nitric oxide precursor.

Hormonally active phytochemicals and vertebrate evolution.

Living plants produce a diversity of chemicals that share structural and functional properties with vertebrate hormones. Wildlife species interact with these chemicals either through consumption of plant materials or aquatic exposure. Accumulating evidence shows that exposure to these hormonally active phytochemicals (HAPs) often has consequences for behavior, physiology, and fecundity. These fitness effects suggest there is potential for an evolutionary response by vertebrates to HAPs. Here, we explore the toxicological HAP-vertebrate relationship in an evolutionary framework and discuss the potential for vertebrates to adapt to or even co-opt the effects of plant-derived chemicals that influence fitness. We lay out several hypotheses about HAPs and provide a path forward to test whether plant-derived chemicals influence vertebrate reproduction and evolution. Studies of phytochemicals with direct impacts on vertebrate reproduction provide an obvious and compelling system for studying evolutionary toxicology. Furthermore, an understanding of whether animal populations evolve in response to HAPs could provide insightful context for the study of rapid evolution and how animals cope with chemical agents in the environment.

Environmentally relevant concentrations of nitrate increase plasma testosterone concentrations in female American alligators (Alligator mississippiensis).

Anthropogenic nitrogen is a ubiquitous environmental contaminant that is contributing to the degradation of freshwater, estuarine, and coastal ecosystems worldwide. The effects of environmental nitrate, a principal form of nitrogen, on the health of aquatic life is of increasing concern. We exposed female American alligators to three concentrations of nitrate (0.7, 10 and 100mg/L NO3-N) for a duration of five weeks and five months from hatch. We assessed growth, plasma sex steroid and thyroid hormone concentrations, and transcription levels of key genes involved in steroidogenesis (StAR, 3ß-HSD, and P450scc) and hepatic clearance (Cyp1a, Cyp3a). Exposure to 100mg/L NO3-N for both five weeks and five months resulted in significantly increased plasma testosterone (T) concentrations compared with alligators in the reference treatment. No differences in 17ß-estradiol, progesterone, or thyroid hormones were observed, nor were there differences in alligator weight or the mRNA abundance of steroidogenic or hepatic genes. Plasma and urinary nitrate concentrations increased with increasing nitrate treatment levels, although relative plasma concentrations of nitrate were significantly lower in five month, versus five week old animals, possibly due to improved kidney function in older animals. These results indicate that environmentally relevant concentrations of nitrate can increase circulating concentrations of T in young female alligators.

Integrative and comparative reproductive biology: From alligators to xenobiotics.

Dr. Louis J. Guillette Jr. thought of himself as a reproductive biologist. However, his interest in reproductive biology transcended organ systems, life history stages, species, and environmental contexts. His integrative and collaborative nature led to diverse and fascinating research projects conducted all over the world. He doesn't leave us with a single legacy. Instead, he entrusts us with several. The purpose of this review is to highlight those legacies, in both breadth and diversity, and to illustrate Dr. Guillette's grand contributions to the field of reproductive biology. He has challenged the field to reconsider how we think about our data, championed development of novel and innovative techniques to measure endocrine function, helped define the field of endocrine disruption, and lead projects to characterize new endocrine disrupting chemicals. He significantly influenced our understanding of evolution, and took bold and important steps to translate all that he has learned into advances in human reproductive health. We hope that after reading this manuscript our audience will appreciate and continue Dr. Guillette's practice of open-minded and passionate collaboration to understand the basic mechanisms driving reproductive physiology and to ultimately apply those findings to protect and improve wildlife and human health.

Taste and physiological responses to glucosinolates: seed predator versus seed disperser.

In contrast to most other plant tissues, fleshy fruits are meant to be eaten in order to facilitate seed dispersal. Although fleshy fruits attract consumers, they may also contain toxic secondary metabolites. However, studies that link the effect of fruit toxins with seed dispersal and predation are scarce. Glucosinolates (GLSs) are a family of bitter-tasting compounds. The fleshy fruit pulp of Ochradenus baccatus was previously found to harbor high concentrations of GLSs, whereas the myrosinase enzyme, which breaks down GLSs to produce foul tasting chemicals, was found only in the seeds. Here we show the differential behavioral and physiological responses of three rodent species to high dose (80%) Ochradenus' fruits diets. Acomys russatus, a predator of Ochradenus' seeds, was the least sensitive to the taste of the fruit and the only rodent to exhibit taste-related physiological adaptations to deal with the fruits' toxins. In contrast, Acomys cahirinus, an Ochradenus seed disperser, was more sensitive to a diet containing the hydrolyzed products of the GLSs. A third rodent (Mus musculus) was deterred from Ochradenus fruits consumption by the GLSs and their hydrolyzed products. We were able to alter M. musculus avoidance of whole fruit consumption by soaking Ochradenus fruits in a water solution containing 1% adenosine monophosphate, which blocks the bitter taste receptor in mice. The observed differential responses of these three rodent species may be due to evolutionary pressures that have enhanced or reduced their sensitivity to the taste of GLSs.

Seasonal reproduction of male Gambusia holbrooki (eastern mosquitofish) from two Florida lakes.

Sixteen monthly collections of adult male Gambusia holbrooki (eastern mosquitofish) were obtained from two lakes in central Florida, USA. Lake Woodruff and Lake Apopka are 36 miles apart, but differ in several environmental parameters. Compared with Lake Woodruff, Lake Apopka is warmer, more shallow in sampling areas (particularly during drought conditions; approximately 15-90 cm in Lake Apopka versus 60-120 cm in Lake Woodruff), more turbid, and more heavily contaminated with nutrients and industrial and agricultural chemicals. Here, we present detailed information on seasonal reproduction patterns in mosquitofish in their native range and compare patterns between fish from the two lakes. Male mosquitofish were reproductively active from spring through fall. Spermatogenesis, which is regulated in part by 11-ketotestosterone, ceased in October, and fish stored spermatozoa through the winter for immediate fertilization of offspring in the spring. Compared with Lake Woodruff, fish from Lake Apopka tended to be larger and have longer gonopodia and greater gonado- and hepato-somatic indices (GSI and HSI). High GSI in Apopka fish correlated with greater spermatid production, but fewer mature spermatozoa and either the same or lower sperm counts and sperm viability. Taken together, these observations suggest that differentiation of spermatids to spermatozoa is disrupted in Apopka fish, leading to reductions in fertility in some months. Delivery of sperm to females could also be affected in Apopka fish, which exhibit lower prevalence of efferent duct tissue in the testes during the summer.

Influence of Nitrate and Nitrite on Thyroid Hormone Responsive and Stress-Associated Gene Expression in Cultured Rana catesbeiana Tadpole Tail Fin Tissue.

Nitrate and nitrite are common aqueous pollutants that are known to disrupt the thyroid axis. In amphibians, thyroid hormone (TH)-dependent metamorphosis is affected, although whether the effect is acceleration or deceleration of this developmental process varies from study to study. One mechanism of action of these nitrogenous compounds is through alteration of TH synthesis. However, direct target tissue effects on TH signaling are hypothesized. The present study uses the recently developed cultured tail fin biopsy (C-fin) assay to study possible direct tissue effects of nitrate and nitrite. Tail biopsies obtained from premetamorphic Rana catesbeiana tadpoles were exposed to 5 and 50 mg/L nitrate (NO(3)-N) and 0.5 and 5 mg/L nitrite (NO(2)-N) in the absence and presence of 10 nM T(3). Thyroid hormone receptor ß (TRß) and Rana larval keratin type I (RLKI), both of which are TH-responsive gene transcripts, were measured using quantitative real time polymerase chain reaction. To assess cellular stress which could affect TH signaling and metamorphosis, heat shock protein 30, and catalase (CAT) transcript levels were also measured. We found that nitrate and nitrite did not significantly change the level of any of the four transcripts tested. However, nitrate exposure significantly increased the heteroscedasticity in response of TRß and RLKI transcripts to T(3). Alteration in population variation in such a way could contribute to the previously observed alterations of metamorphosis in frog tadpoles, but may not represent a major mechanism of action.

Seasonal reproductive patterns of female Gambusia holbrooki from two Florida lakes.

Lake Apopka in central Florida (USA) is significantly contaminated with a variety of chemicals including anthropogenic nutrients, organochlorine pesticides like dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE), and multiple congeners of polychlorinated biphenyls (PCBs). Our laboratory has previously documented a number of reproductive abnormalities in alligators from Lake Apopka, compared with alligators captured from Lake Woodruff, a nearby reference lake. We conducted the present study to investigate if another native vertebrate, Gambusia holbrooki (eastern mosquitofish), is similarly affected. Adult female mosquitofish were collected from Lake Apopka and Lake Woodruff monthly for 16 months to document seasonal and lake-associated variation in reproductive patterns. In contrast to fish from Lake Woodruff (reference), females from Lake Apopka exhibited earlier and more synchronized spring ovarian recrudescence, increased body size, increased fecundity, increased adjusted hepatic weight, and more extreme fluctuations in muscle estradiol concentrations in most months. Endocrine disruption, consistent with other studies and Lake Apopka's pollution profile, is one explanation for these findings. Other environmental and physiological factors are also addressed. However, the higher fecundity among Apopka females suggests that, unlike Apopka alligators, Apopka mosquitofish are not impacted at the population level.

Female reproductive disorders: the roles of endocrine-disrupting compounds and developmental timing.

OBJECTIVE: To evaluate the possible role of endocrine-disrupting compounds (EDCs) on female reproductive disorders emphasizing developmental plasticity and the complexity of endocrine-dependent ontogeny of reproductive organs. Declining conception rates and the high incidence of female reproductive disruptions warrant evaluation of the impact of EDCs on female reproductive health. DESIGN: Publications related to the contribution of EDCs to disorders of the ovary (aneuploidy, polycystic ovary syndrome, and altered cyclicity), uterus (endometriosis, uterine fibroids, fetal growth restriction, and pregnancy loss), breast (breast cancer, reduced duration of lactation), and pubertal timing were identified, reviewed, and summarized at a workshop. CONCLUSION(S): The data reviewed illustrate that EDCs contribute to numerous human female reproductive disorders and emphasize the sensitivity of early life-stage exposures. Many research gaps are identified that limit full understanding of the contribution of EDCs to female reproductive problems. Moreover, there is an urgent need to reduce the incidence of these reproductive disorders, which can be addressed by correlative studies on early life exposure and adult reproductive dysfunction together with tools to assess the specific exposures and methods to block their effects. This review of the EDC literature as it relates to female health provides an important platform on which women's health can be improved.

Environmental exposures and gene regulation in disease etiology.

Health or disease is shaped for all individuals by interactions between their genes and environment. Exactly how the environment changes gene expression and how this can lead to disease are being explored in a fruitful new approach to environmental health research, representative studies of which are reviewed here. We searched Web of Science and references of relevant publications to understand the diversity of gene regulatory mechanisms affected by environmental exposures with disease implications. Pharmaceuticals, pesticides, air pollutants, industrial chemicals, heavy metals, hormones, nutrition, and behavior can change gene expression through a broad array of gene regulatory mechanisms. Furthermore, chemically induced changes in gene regulation are associated with serious and complex human diseases, including cancer, diabetes and obesity, infertility, respiratory diseases, allergies, and neurodegenerative disorders such as Parkinson and Alzheimer diseases. The reviewed studies indicate that genetic predisposition for disease is best predicted in the context of environmental exposures. And the genetic mechanisms investigated in these studies offer new avenues for risk assessment research. Finally, we are likely to witness dramatic improvements in human health, and reductions in medical costs, if environmental pollution is decreased.

Environmental influences on fertility: can we learn lessons from studies of wildlife?

Wildlife are good models for understanding the impacts of environmental contamination on fertility because [1] exposure doses are representative of actual contaminant mixtures and concentrations in the environment, [2] wildlife populations are more genetically diverse than laboratory animal populations, and [3] both individual and population level effects of fertility compromise can be observed.

Environmental exposures and gene regulation in disease etiology: [review]

Health or disease is shaped for all individuals by interactions between their genes and environment. Exactly how the environment changes gene expression and how this can lead to disease are being explored in a fruitful new approach to environmental health research, representative studies of which are reviewed here. We searched Web of Science and references of relevant publications to understand the diversity of gene regulatory mechanisms affected by environmental exposures with disease implications. Pharmaceuticals, pesticides, air pollutants, industrial chemicals, heavy metals, hormones, nutrition, and behavior can change gene expression through a broad array of gene regulatory mechanisms. Furthermore, chemically induced changes in gene regulation are associated with serious and complex human diseases, including cancer, diabetes and obesity, infertility, respiratory diseases, allergies, and neurodegenerative disorders such as Parkinson and Alzheimer diseases. The reviewed studies indicate that genetic predisposition for disease is best predicted in the context of environmental exposures. And the genetic mechanisms investigated in these studies offer new avenues for risk assessment research. Finally, we are likely to witness dramatic improvements in human health, and reductions in medical costs, if environmental pollution is decreased.

Saúde e doença resultam da interação entre genes e o ambiente em que os indivíduos vivem. Vários estudos analisados neste artigo vêm explorando, com bons resultados, o modo como o ambiente modifica a expressão dos genes e como isso pode provocar doenças. Buscamos nas bases de dados científicas e referências de publicações relevantes, estudos que nos levaram a entender a diversidade de formas pelas quais os mecanismos regulatórios dos genes são afetados por exposições ambientais e implicam adoecimento. Medicamentos, pesticidas, poluentes do ar, produtos químicos, metais pesados, hormônios, produtos de nutrição e comportamentos podem mudar a expressão genética por meio de uma quantidade enorme de mecanismos regulatórios dos genes. Ademais, mudanças quimicamente induzidas na regulação do gene estão associadas a enfermidades graves e complexas, como é o caso do câncer, diabetes, infertilidade, doenças respiratórias, alergias e problemas neurodegenerativos como o mal de Parkinson e Alzheimer. Os estudos revistos indicam que uma predisposição genética para determinada doença é melhor prevista no contexto das exposições ambientais. E os mecanismos genéticos examinados nesses estudos oferecem novos caminhos para pesquisas sobre avaliação de risco.

Alligators, contaminants and steroid hormones.

Steroids are essential for successful reproduction in all vertebrate species. Over the last several decades, extensive research has indicated that exposure to various environmental pollutants can disrupt steroidogenesis and steroid signaling. Although steroidogenesis is regulated by the hypothalamic-pituitary axis, it is also modified by various paracrine and autocrine factors. Furthermore, the classical two-cell model of steroidogenesis in the developing ovarian follicle, involving the granulosa and theca cells in mammals, may not be universal. Instead, birds and probably reptiles use the two thecal compartments (theca interna and theca externa) as sites of steroid production. We have documented that embryonic or juvenile exposure to a complex mixture of contaminants from agricultural and storm water runoff leads to altered steroid hormone profiles in American alligators. Our observations suggest that alterations in plasma steroid hormone concentrations are due in part to altered gene expression, modified hepatic biotransformation and altered gonadal steroidogenesis. Future studies must examine the interplay between endocrine and paracrine regulation in the development and expression of gonadal steroidogenesis in individuals exposed to endocrine disrupting contaminants at various life stages if we are to fully understand potential detrimental outcomes.