RESUMEN
Endocrine disrupting compounds (EDCs) are contaminants ubiquitously found in the environment, which pose a potential threat to aquatic and wetland ecosystems. Caiman latirostris, a crocodilian species that inhabits South American wetlands, is highly sensitive to EDC exposure. Previously, we reported that early postnatal exposure to EDCs such as Bisphenol A (BPA) and 17ß-Estradiol (E2) alters C. latirostris oviduct differentiation. The aim of this work was to elucidate the molecular mechanisms behind this alteration. To accomplish this, we established the ontogenic changes in histological features and the expression of Wnt-7a, Wnt-5a, ß-catenin, FoxA2, desmin, and alpha smooth muscle actin (α-SMA) in the oviduct of C. latirostris. Then, we evaluated the effects of BPA and E2 exposure on these histological features and protein expressions. Our results showed that during the postnatal differentiation of the oviduct the presence of histological features related to adenogenesis is associated with the levels of expression of FoxA2, ß-catenin, Wnt-5a and Wnt-7a. Early postnatal exposure to BPA and E2 decreased the presence of histological features related to adenogenesis and altered the levels of expression of FoxA2, ß-catenin, Wnt-5a and Wnt-7a, as well as the desmin/α-SMA ratio. These findings suggest that altered levels of Wnt-7a, Wnt-5a, ß-catenin and FoxA2 could play a role in the BPA and E2-induced alteration in oviduct differentiation in C. latirostris. Thus, impaired adenogenesis and, probably, impaired reproduction in wildlife naturally exposed to BPA and other estrogenic agonists cannot be completely ruled out.
Asunto(s)
Caimanes y Cocodrilos/fisiología , Estrógenos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Compuestos de Bencidrilo , Diferenciación Celular/efectos de los fármacos , Ecosistema , Disruptores Endocrinos/toxicidad , Estradiol/farmacología , Femenino , Hormonas Esteroides Gonadales , Humanos , Oviductos/efectos de los fármacos , Fenoles , Reproducción/efectos de los fármacos , beta CateninaRESUMEN
Agricultural pesticides represent a significant class of endocrine-disrupting chemicals (EDCs) to which non-target organisms around the world are constantly exposed. Laboratory studies have found strong evidence showing the endocrine-disruptive potential of these pesticides at environmentally relevant exposure levels. Since the field of endocrine disruption continues to grow in richness and complexity, this review aims to provide an update on the effects of two agricultural pesticides that act as EDCs: atrazine and endosulfan. We will focus mainly on the effects on crocodilians due to their worldwide occurrence in tropical and sub-tropical wetland ecosystems and their ecological and physiological features, which render them vulnerable to exposure to pesticides with endocrine-disrupting action at all life stages. The results here reviewed provide important insights into the effects of hormonally active agricultural pesticides at cellular, tissue, and organ levels in the reproductive system of crocodiles. A better understanding of the effects of exposure to environmentally relevant doses of EDCs on the reproductive system of crocodilians will contribute to protect and improve the health of both wildlife species and humans.
Asunto(s)
Caimanes y Cocodrilos , Genitales/efectos de los fármacos , Plaguicidas/farmacología , Especies Centinela , Agroquímicos/farmacología , Agroquímicos/toxicidad , Caimanes y Cocodrilos/fisiología , Animales , Animales Salvajes , Organismos Acuáticos/efectos de los fármacos , Disruptores Endocrinos/farmacología , Disruptores Endocrinos/toxicidad , Sistema Endocrino/efectos de los fármacos , Exposición a Riesgos Ambientales/análisis , Genitales/fisiología , Humanos , Plaguicidas/toxicidadRESUMEN
Bisphenol A (BPA) is a compound used in the polymerization of plastic polycarbonates. It is an endocrine disruptor and it has been postulated to be an obesogen. Our objective was to determine the influence of perinatal exposure to BPA on body weight, hormone levels, metabolic parameters and hypothalamic signals that regulate food intake and kisspeptin system in adult male rats. Male rats were exposed to 50⯵g/kg/day of BPA or vehicle from day 9 of gestation to weaning in the drinking water. Since weaning, they were fed with control or high fat diet for 20 weeks. Perinatal exposure to BPA impaired glucose homeostasis, induced obesity and increased food intake in adult male rats altering hypothalamic signals, partially mimicking and/or producing an exacerbation of the effects of feeding fat diet. We also observed an increase in kisspeptin expression by BPA exposure. Evidences shown in this work support the metabolic disruptor hypothesis for BPA.
Asunto(s)
Compuestos de Bencidrilo/efectos adversos , Disruptores Endocrinos/efectos adversos , Kisspeptinas/metabolismo , Obesidad/inducido químicamente , Fenoles/efectos adversos , Efectos Tardíos de la Exposición Prenatal/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Femenino , Glucosa/metabolismo , Masculino , Obesidad/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , RatasRESUMEN
The broad-snouted caiman (Caiman latirostris) is a crocodilian species that inhabits South American wetlands. As in all other crocodilians, the egg incubation temperature during a critical thermo-sensitive window (TSW) determines the sex of the hatchlings, a phenomenon known as temperature-dependent sex determination (TSD). In C. latirostris, we have shown that administration of 17-ß-estradiol (E2) during the TSW overrides the effect of the male-producing temperature, producing phenotypic females (E2SD-females). Moreover, the administration of E2 during TSW has been proposed as an alternative way to improve the recovery of endangered reptile species, by skewing the population sex ratio to one that favors females. However, the ovaries of E2SD-female caimans differ from those of TSD-females. In crocodilians, the external genitalia (i.e. clitero-penis structure or phallus) are sexually dimorphic and hormone-sensitive. Despite some morphological descriptions aimed to facilitate sexing, we found no available data on the C. latirostris phallus histoarchitecture or hormone dependence. Thus, the aims of this study were: (1) to establish the temporal growth pattern of the phallus in male and female caimans; (2) to evaluate histo-morphological features and the expression of estrogen receptor alpha (ERα) and androgen receptor (AR) in the phallus of male and female pre-pubertal juvenile caimans; and (3) to determine whether the phallus of TSD-females differs from the phallus of E2SD-females. Our results demonstrated sexually dimorphic differences in the size and growth dynamics of the caiman external genitalia, similarities in the shape and spatial distribution of general histo-morphological compartments, and sexually dimorphic differences in innervation, smooth muscle fiber distribution, collagen organization, and ERα and AR expressions. The external genitalia of E2SD-females differed from that of TSD-females in many histological features and in the expression of ERα and AR, resembling patterns described in males. Our results alert on the effects of estrogen agonist exposure during TSW and suggest that caution must be taken regarding the use of E2SD as a procedure for wildlife population management.
Asunto(s)
Caimanes y Cocodrilos/fisiología , Genitales Femeninos/fisiología , Hormonas Esteroides Gonadales/metabolismo , Procesos de Determinación del Sexo , Temperatura , Caimanes y Cocodrilos/anatomía & histología , Animales , Proliferación Celular/efectos de los fármacos , Colágeno/metabolismo , Desmina/metabolismo , Femenino , Genitales Femeninos/citología , Genitales Femeninos/crecimiento & desarrollo , Masculino , Receptores de Superficie Celular/metabolismoRESUMEN
Caiman latirostris is a South American crocodilian species characterized as a sentinel of the presence of endocrine-disrupting compounds (EDCs). Evaluating developmental events in hormone-dependent organs, such as the oviduct, is crucial to understand physiological postnatal development, to identify putative periods of exposure sensitive to EDCs, and/or to identify biomarkers useful to evaluate the effects of EDC exposure. In this study, we describe the histomorphological features of C. latirostris oviducts by establishing the ontogeny of changes at cellular, tissue and molecular levels from the neonatal to the pre-pubertal juvenile stages. Since the histological diagnosis of the adenogenic oviduct lies on a group of features, here we defined a histofunctional score system and a cut-off value to distinguish between preadenogenic and adenogenic oviducts. Our results showed that the maturation of the C. latirostris oviduct is completed postnatally and characterized by changes that mimic the pattern of histological modifications described for the mammalian uterus. Ontogenic changes in the oviductal epithelium parallel changes at subepithelial level, and include collagen remodeling and characteristic spatial-temporal patterns of α-actin and desmin. The expression pattern of estrogen receptor alpha and progesterone receptor evidenced that, even at early postnatal developmental stages, the oviduct of C. latirostris is a target organ of endogenous and environmental hormones. Besides, oviductal adenogenesis seems to be an estrogen-dependent process. Results presented here provide not only insights into the histophysiological aspect of caiman female reproductive ducts but also new tools to better characterize caimans as sentinels of endocrine disruption.