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1.
Mar Pollut Bull ; 145: 126-137, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31590768

RESUMO

The Bilbao estuary (SE Bay of Biscay) is a recovering ecosystem whose sediments are still contaminated. They represent a potential risk for the biota including benthic and demersal species living in direct contact with the sediment. In this context, the present study aims to survey trends of the health status of the Bilbao estuary based on sediment chemistry and sole (Solea spp.) histopathology. Monitoring campaigns were carried out every autumn from 2011 to 2017 along the estuary. Contaminant levels were measured in sediments; liver, gills and gonads of juvenile fish were collected for histopathology. Overall, contaminant levels fluctuated throughout the years, with highest values recorded in the earlier years of the study period. Sole histopathology showed alterations of mild severity. Results permitted to assess the environmental health status of the Bilbao estuary during 7 years, although no clear temporal trend was detected. Longer-term monitoring programmes are necessary to confirm the ecosystem recovery.


Assuntos
Linguados/fisiologia , Sedimentos Geológicos/química , Animais , Ecossistema , Ecotoxicologia , Monitoramento Ambiental/métodos , Estuários , Feminino , Brânquias/química , Brânquias/patologia , Gônadas/química , Gônadas/patologia , Fígado/química , Fígado/patologia , Masculino , Metais/análise , Espanha , Poluentes Químicos da Água/análise
2.
Medicine (Baltimore) ; 98(34): e16845, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441858

RESUMO

RATIONALE: The gonads of patients with Turner syndrome (TS) were previously thought to be funicular. There was no increase in androgen level. The gonad that is testis should be taken into account when the patient's serum testosterone level was abnormal and hypothalamic-pituitary-adrenal disease was excepted. PATIENT CONCERNS: A 16-year-old girl was admitted to our hospital because of chromosomal abnormalities and elevated androgen levels. DIAGNOSIS: Turner syndrome could be diagnosed since her chromosome karyotype was 45, XO. INTERVENTIONS: The patient was given bilateral gonadectomy and hormone replacement therapies. OUTCOME: The level of the patient's serum testosterone was <0.45 nmol/L 2 days after the operation. Postoperative pathology showed that her right gonad was testicular tissue. The patient's menstruation was normal after the treatment of hormone replacement therapy. LESSONS: All TS patients should get Y chromosome material screening. Gonadectomy could be done for Turner syndrome patients who have hyperandrogenism or Y chromosome material.


Assuntos
Gônadas/patologia , Hiperandrogenismo/complicações , Síndrome de Turner/complicações , Adolescente , Feminino , Gônadas/cirurgia , Humanos , Reação em Cadeia da Polimerase , Testosterona/sangue
3.
Arch Environ Contam Toxicol ; 77(3): 390-408, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31422435

RESUMO

One of the direct causes of biodiversity loss is environmental pollution resulting from the use of chemicals. Different kinds of chemicals, such as persistent organic pollutants and some heavy metals, can be endocrine disruptors, which act at low doses over a long period of time and have a negative effect on the reproductive and thyroid system in vertebrates worldwide. Research on the effects of endocrine disruptors and the use of bioindicators in neotropical ecosystems where pressure on biodiversity is high is scarce. In Chile, although endocrine disruptors have been detected at different concentrations in the environments of some ecosystems, few studies have been performed on their biological effects in the field. In this work, Xenopus laevis (African clawed frog), an introduced species, is used as a bioindicator for the presence of endocrine disruptors in aquatic systems with different degrees of contamination in a Mediterranean zone in central Chile. For the first time for Chile, alterations are described that can be linked to exposure to endocrine disruptors, such as vitellogenin induction, decreased testosterone in male frogs, and histological changes in gonads. Dioxin-like and oestrogenic activity was detected in sediments at locations where it seem to be related to alterations found in the frogs. In addition, an analysis of land use/cover use revealed that urban soil was the best model to explain the variations in frog health indicators. This study points to the usefulness of an invasive species as a bioindicator for the presence of endocrine-disruptive chemicals.


Assuntos
Disruptores Endócrinos/toxicidade , Biomarcadores Ambientais , Exposição Ambiental/análise , Poluição Ambiental/efeitos adversos , Xenopus laevis/fisiologia , Animais , Linhagem Celular Tumoral , Chile , Ecossistema , Ecotoxicologia/métodos , Disruptores Endócrinos/análise , Poluentes Ambientais/toxicidade , Feminino , Sedimentos Geológicos/análise , Gônadas/patologia , Humanos , Espécies Introduzidas , Masculino , Reprodução , Testosterona/metabolismo , Vitelogeninas/metabolismo
4.
Environ Toxicol ; 34(11): 1255-1262, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31298479

RESUMO

Progesterone (P4) is a biologically active steroid hormone that is involved in the regulation of oocyte growth and maturation, as well as development of the endometrium and implantation in the uterus of humans. It can also stimulate oocyte maturation in female fish, as well as spermatogenesis and sperm motility in male fish. Thus, P4 has been extensively used in human and animal husbandry as a typical progestin. However, P4 remaining in the water environment will pose a potential hazard to aquatic organisms. For example, it can interfere with sex differentiation and reproduction in aquatic vertebrates such as fish. Therefore, we investigated the effects of prolonged progesterone exposure on the expression of genes related to circadian rhythm signaling and the hypothalamic-pituitary-gonadal (HPG) axes in Yellow River Carp, which may have a potential impact on their sex differentiation. Our results suggested that P4 exposure altered the expression of genes related to circadian rhythm signaling, which can lead to disorders in the endocrine system and regulate the HPG axes-related activities. Furthermore, the expression of genes related to the HPG axes was also altered, which might affect gonadal development and the reproductive systems of Yellow River Carp. In addition, these changes may provide a plausible mechanism for the observed shifts in their sex ratio toward females.


Assuntos
Ritmo Circadiano/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Progesterona/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Animais , Carpas/crescimento & desenvolvimento , Carpas/metabolismo , Feminino , Gônadas/efeitos dos fármacos , Gônadas/patologia , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismo , Diferenciação Sexual/efeitos dos fármacos , Razão de Masculinidade , Transcrição Genética/efeitos dos fármacos
5.
Environ Sci Pollut Res Int ; 26(23): 23328-23336, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31197669

RESUMO

A wide range of endocrine disruptor compounds are routinely discharged to the ecosystem. Water contaminated with these compounds has a potential effect on the reproductive physiology of aquatic organisms as well as humans. In the present study, we tested the effect of the steroid estrogen, 17ß-estradiol, on Biomphalaria alexandrina, a snail species that is widely distributed in Egypt and that acts as an intermediate host for the human blood fluke, Schistosoma mansoni. The effects of exposure to 0.3 mg/L and 1 mg/L 17ß-estradiol on fecundity (MX) and reproductive rate (R0) of B. alexandrina were recorded. In addition, levels of steroid sex hormones and antioxidants in the hemolymph and ovotestis (OT) of exposed snails were measured. Histopathological changes in the OT of B. alexandrina were also investigated. Exposure to 0.3 mg/L and 1 mg/L 17ß-estradiol caused a significant increase in the number of egg masses per snail after 3 weeks and 1 week of exposure for the two tested concentrations compared with unexposed controls. An increase in the levels of progesterone hormone was recorded in the hemolymph of exposed snails in comparison with unexposed controls. Additionally, levels of the antioxidant enzyme glutathione (GSH) were increased in the hemolymph and OT tissues of snails after 2 and 4 weeks of exposure. Histopathological sections in the OT revealed an increase in the oocyte and a decrease in the sperm densities after 2 weeks and this effect was restored to normal conditions after 4 weeks of exposure to both tested concentrations. The current results indicate that B. alexandrina is sensitive to 17ß-estradiol and can therefore be used as bioindicator and model organism for the assessment of water pollution with endocrine disruptor compounds.


Assuntos
Biomphalaria/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Monitoramento Ambiental/métodos , Estradiol/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Ecossistema , Egito , Biomarcadores Ambientais/efeitos dos fármacos , Fertilidade/efeitos dos fármacos , Gônadas/efeitos dos fármacos , Gônadas/patologia , Hemolinfa/efeitos dos fármacos , Hemolinfa/metabolismo , Humanos
6.
Semin Oncol ; 46(2): 107-111, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31076171

RESUMO

BACKGROUD: Germ cell tumors (GCTs) are a group of neoplasms usually arising in the gonads, and very rarely in sites outside the gonads, mainly in the retroperitoneum, the anterior mediastinum, and pineal gland or the coccyx (mainly in childhood). The prognosis of nonseminoma primary mediastinal GCTs (PMGCTs), is considered to be poorer compared to its retroperitoneal or gonadal counterparts and, according to the International Germ Cell Cancer Collaborative Group, it is considered by definition as a "poor risk" disease. MATERIAL AND METHODS: Our review highlights the clinical features, prognostic factors, and therapeutic strategies in PMGCTs, as described in medical literature. So far available data were obtained through a Medline search of English-language papers. RESULTS: Due to the rarity of the disease, there are no prospective studies comparing different treatment strategies. For this reason, oncology societies recommend treating PMGCTs like other GCTs, according to general risk categories. CONCLUSION: Because of the rarity of the disease, poor categorization, and the lack of novel therapeutic strategies, an International database is required to obtain more information on these tumors. Additional efforts should be done, with the aims to find effective novel therapeutic agents.


Assuntos
Neoplasias do Mediastino/terapia , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Testiculares/terapia , Gônadas/patologia , Humanos , Neoplasias do Mediastino/patologia , Mediastino/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , Prognóstico , Fatores de Risco , Neoplasias Testiculares/patologia
7.
Horm Behav ; 112: 65-76, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30959023

RESUMO

Sex differences in the anatomy and physiology of the vertebrate preoptic area (POA) arise during development, and influence sex-specific reproductive functions later in life. Relative to masculinization, mechanisms for feminization of the POA are not well understood. The purpose of this study was to induce sex change from male to female in the anemonefish Amphiprion ocellaris, and track the timing of changes in POA cytoarchitecture, composition of the gonads and circulating sex steroid levels. Reproductive males were paired together and then sampled after 3 weeks, 6 months, 1 year and 3 years. Results show that as males change sex into females, number of medium cells in the anterior POA (parvocellular region) approximately double to female levels over the course of several months to 1 year. Feminization of gonads, and plasma sex steroids occur independently, on a variable timescale, up to years after POA sex change has completed. Findings suggest the process of POA feminization is orchestrated by factors originating from within the brain as opposed to being cued from the gonads, consistent with the dominant hypothesis in mammals. Anemonefish provide an opportunity to explore active mechanisms responsible for female brain development in an individual with male gonads and circulating sex steroid levels.


Assuntos
Feminização/etiologia , Feminização/patologia , Gônadas/fisiologia , Perciformes/fisiologia , Área Pré-Óptica/fisiologia , Animais , Encéfalo/patologia , Contagem de Células , Feminino , Feminização/sangue , Feminização/veterinária , Hormônios Esteroides Gonadais/sangue , Gônadas/patologia , Masculino , Perciformes/metabolismo , Área Pré-Óptica/patologia , Caracteres Sexuais , Diferenciação Sexual/fisiologia , Testículo/patologia
8.
Aquat Toxicol ; 211: 181-192, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31003043

RESUMO

Inappropriate processing and disposal of electronic waste contributes to the contamination of aquatic systems by various types of pollutants such as the rare-earth elements (REE) in which lanthanum (La) is included. Knowledge on the toxicity of these elements in marine organisms is still scarce when compared to other metals such as mercury (Hg) and arsenic (As). Therefore, this study aims to assess the toxicity of La on the mussel Mytilus galloprovincialis, considered a good bioindicator of aquatic pollution, through the analysis of metabolic, oxidative stress, neurotoxicity and histopathological markers. Organisms were exposed to different concentrations of La for a period of 28 days (0, 0.1, 1, 10 mg/L) under controlled temperature (18 °C ± 1.0) and salinity (30 ± 1) conditions. La concentrations in mussels increased in higher exposure concentrations. La exposure demonstrated a biochemical response in mussels, evidenced by lowered metabolism and accumulation of energy reserves, activation of the antioxidant defences SOD and GPx as well as the biotransformation enzymes GSTs, especially at intermediate concentrations. Despite oxidative stress being shown by a decrease in GSH/GSSG, oxidative damage was avoided as evidenced by lower LPO and PC levels. Inhibition of the enzyme AChE demonstrated the neurotoxicity of La in this species. Histopathological indices were significantly different from the control group, indicating impacts in gonads, gills and digestive glands of mussels due to La. These results show that La can be considered a risk for marine organisms and thus its discharge into the environment should be monitored.


Assuntos
Lantânio/toxicidade , Mytilus/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Biotransformação , Sistema Digestório/efeitos dos fármacos , Sistema Digestório/metabolismo , Sistema Digestório/patologia , Ecotoxicologia , Biomarcadores Ambientais/efeitos dos fármacos , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Brânquias/patologia , Gônadas/efeitos dos fármacos , Gônadas/metabolismo , Gônadas/patologia , Lantânio/metabolismo , Mytilus/metabolismo , Poluentes Químicos da Água/metabolismo
9.
Chemosphere ; 225: 535-547, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30901648

RESUMO

Pesticides are distributed to different degrees in surface water and sediment, thus, risks of toxicity and adverse impacts to physiology of resident species could be determined by their microhabitat (sub-habitat) associations, either water column or sediment. River Owan receives pesticide input from diffuse sources from adjacent farmlands. Surface water, sediment and fish samples [(Pelagic: Tilapia zilli (n = 92) and benthic: Neochanna diversus (n = 59), Clarias gariepinus (n = 68) were collected within the catchment area across seasons for 18-months (August 2016-January 2018) and measured for pesticide levels. Testicular and Ovarian tissue samples across the three species were also examined for pathological alterations. Individual pesticide concentrations in surface water and sediment exceeded international allowable limits, while concentration of pesticide residues in tissues of benthic species was higher compared to pelagic fish. Histopathological assessment revealed a higher incidence of ovarian disruption including atretic follicles, intersex and disorganization of ovarian structure in benthic (bottom-dwelling) fish (C. gariepinus and N. diversus) compared to pelagic (water-column) fish (T. zilli). Males benthic fish species also recorded more severe anomalies, compared to pelagic fish. The damages and anomalies observed in ovarian and testicular tissue indicate chronic responses to pollutant exposure, and implicates the elevation of pesticide concentrations in surface water and sediment above permissible limits. The higher incidence of anomalies recorded for benthic species compared to pelagic species, indicates greater risks of reproductive disruption and could be associated with the microhabitat preferences (water-column or sediment).


Assuntos
Transtornos do Desenvolvimento Sexual/induzido quimicamente , Gônadas/patologia , Ovário/patologia , Resíduos de Praguicidas/toxicidade , Praguicidas/toxicidade , Testículo/patologia , Poluentes Químicos da Água/toxicidade , Animais , Peixes-Gato/anatomia & histologia , Ecossistema , Feminino , Masculino , Nigéria , Resíduos de Praguicidas/análise , Praguicidas/análise , Rios/química , Alimentos Marinhos , Tilápia/anatomia & histologia , Poluentes Químicos da Água/análise
10.
Braz J Microbiol ; 50(1): 313-320, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30637657

RESUMO

An outbreak of infectious bronchitis caused by the IBVPR03 strain of the Massachusetts genotype affected H-120 vaccinated laying hens in South Brazil. We investigated the cross protection of the vaccine by assessing the traqueal ciliostasis, virus recovery, and histopathological changes typically observed in the respiratory tract. Although the IBVPR03 strain is S1-genotyped as Massachusetts with a high genomic similarity to the H-120 vaccine strains, surprisingly, we found no tropism or pathogenicity to the trachea in birds infected with this strain. On the other hand, we observed ovarian and testicle lesions. Here, we show that, despite belonging in the Massachusetts genotype, the IBVPR03 pathotype differs from the expected respiratory pattern, causing instead marked histopathological changes in the gonads, so far not associated with this group.


Assuntos
Infecções por Coronavirus/veterinária , Gônadas/virologia , Vírus da Bronquite Infecciosa/isolamento & purificação , Doenças das Aves Domésticas/virologia , Animais , Brasil , Galinhas , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Feminino , Genótipo , Gônadas/patologia , Vírus da Bronquite Infecciosa/classificação , Vírus da Bronquite Infecciosa/genética , Vírus da Bronquite Infecciosa/patogenicidade , Masculino , Doenças das Aves Domésticas/patologia , Traqueia/patologia , Traqueia/virologia , Virulência
11.
Aquat Toxicol ; 207: 142-152, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30572174

RESUMO

The synthetic estrogen 17α-ethinylestradiol (EE2), ubiquitous in the aquatic environment and commonly detected in sewage effluents, interferes with the endocrine system in multiple ways. Exposure during sensitive windows of development causes persistent effects on fertility, reproductive and non-reproductive behavior in mammals and fish. In the present study, three-spined stickleback (Gasterosteus aculeatus) were exposed to nominal 0 and 20 ng/L EE2 from fertilization to 7 weeks post-hatch. After 8 months of remediation in clean water three non-reproductive behaviors, not previously analyzed in developmentally EE2-exposed progeny of wild-caught fish, were evaluated. Chemical analysis revealed that the nominal 0 and 20 ng/L exposure contained 5 and 30 ng/L EE2, respectively. Therefore, the use of control fish from previous experiments was necessary for comparisons. Fish exposed during development showed significant concentration-dependent reduction in anxiety-like behavior in the scototaxis (light/dark preference) test by means of shorter latency to first entrance to the white compartment, more visits in white, and longer total time in white compared to unexposed fish. In the novel tank test, developmental exposure significantly increased the number of transitions to the upper half of the aquaria. Exposure to EE2 during development did not alter shoal cohesion in the shoaling test compared with unexposed fish but fish exposed to 30 ng/L EE2 had significantly longer latency to leave the shoal and fewer transitions away from the shoal compared to fish exposed to 5 ng/L EE2. Skewed sex ratio with more females, sex reversal in genetic males as well as intersex in males was observed after exposure to 30, but not 5 ng/L EE2. In conclusion, EE2 exposure during development in three-spined stickleback resulted in persistent effects on anxiety-like behaviors. These long-term effects from developmental exposure are likely to be of higher relevance for natural populations than are short-term effects from adult exposure.


Assuntos
Comportamento Animal , Exposição Ambiental , Etinilestradiol/toxicidade , Feminização/induzido quimicamente , Reprodução/efeitos dos fármacos , Smegmamorpha/crescimento & desenvolvimento , Animais , Comportamento Animal/efeitos dos fármacos , Feminino , Gônadas/efeitos dos fármacos , Gônadas/patologia , Masculino , Razão de Masculinidade , Smegmamorpha/genética
12.
Mol Genet Genomic Med ; 6(6): 1053-1067, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30334364

RESUMO

BACKGROUND: Congenital aniridia is a severe autosomal dominant binocular developmental disorder, the primary feature of which is congenital absence or hypoplasia of the iris. PAX6 is the main disease-causing gene of congenital aniridia; inheritance is autosomal dominant. But the current mutations do not fully explain this disorder. METHODS: We investigated the mutation profile of genes related in three Chinese families with congenital aniridia through targeted sequencing technology. And we validated the candidate variants by PCR-based Sanger sequencing. Different degree impairments of islet function were observed in the patients with aniridia by carbohydrate tolerance butter and insulin release tests in our study. RESULTS: We identified four novel mutations of PAX6 from three Chinese families with congenital aniridia, which included heterozygous double mutation c.879_880delCA (p.S294Cfs*46) and c.1124C>G (p.P375R) in Family 1 with three patients, heterozygous frameshift mutation c.308delG (p.P103Qfs*21) in Family 2 with one patient, and c.1192delT (p.S398Pfs*126) in Family 3 with two patients. The three frameshift mutations of PAX6 are co-segregated with the aniridia from controls in the families, but the novel missense mutation is not co-segregated with the phenotype. The frameshift mutations in Family 1 and Family 2 have effects to truncate the protein, but the frameshift mutation in Family 3 will prolong it. We confirmed the phenomenon of male gonadal mosaicism of PAX6 by the sequencing of two linked novel mutations in Family 1. Most of the patients with isolated aniridia have different degrees of islet damage through related clinical tests. CONCLUSION: It is therefore noteworthy that we found different types of pathogenic mutation, which have effects of truncating or prolonging protein leaded by frameshift mutation. Our results of this study extended the pathogenic mutation spectrum of PAX6 for congenital aniridia and demonstrated the male germline chimerism by molecular experiments.


Assuntos
Aniridia/genética , Gônadas/metabolismo , Mosaicismo , Mutação , Fator de Transcrição PAX6/genética , Adolescente , Adulto , Aniridia/patologia , Pré-Escolar , Feminino , Gônadas/patologia , Humanos , Ilhotas Pancreáticas/patologia , Masculino , Pessoa de Meia-Idade , Linhagem
13.
J Fish Biol ; 93(5): 1012-1015, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30267411

RESUMO

This study records the occurrence of a hermaphrodite individual of the apapá Pellona flavipinnis captured in a floodplain area of the Amazon River. Histology of the left gonad revealed the presence of testicular germ cells (spermatocytes and spermatozoa) in the cranial portion and mature ovarian cells (primary and vitellogenic oocytes) in the caudal portion, separated by connective tissue. This is the first record of a hermaphrodite fish of the family Pristigasteridae, order Clupeiformes.


Assuntos
Transtornos do Desenvolvimento Sexual/patologia , Doenças dos Peixes/patologia , Peixes/crescimento & desenvolvimento , Animais , Brasil , Feminino , Gônadas/patologia , Masculino , Ovário/patologia , Rios , Testículo/patologia
14.
Toxicology ; 410: 83-95, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30218681

RESUMO

Graphene oxide (GO) has the potential for wide applications, which necessitates an intensive investigation of its potential hazard on human and environmental health. Even if previous studies show reproductive toxicity in the nematode Caenorhabditis elegans, the mechanisms of reproductive toxicity by GO are poorly understood. To understand the underlying mechanisms of GO-induced reproductive toxicity, we investigated the interaction between GO and C. elegans using Raman spectroscopy, sperm counts produced by spermatogenesis, progeny and analyzed the fatty acid metabolism using molecular techniques. GO-characteristic Raman spectral bands measured throughout C. elegans, brood size and Hoecst staining of dissected gonads clearly showed GO accumulation in the reproductive organs, reduced progeny and low sperm counts, which are possibly direct results of the reproductive toxicity from GO exposure. Interestingly, reduced fatty acid metabolites, such as stearic, oleic, palmitoleic, and palmitic acids, were found with GO exposure. We found that GO increased intestinal fat accumulation in wild type N2, fat-5(tm420), and fat-7(wa36) mutants, whereas it decreased fat storage in the fat-6(tm331) and nhr-49(nr2041) mutants. GO exposure affected C. elegans fat accumulation and consumption, which was possibly regulated by daf-16 and nhr-80 gene activity. Also, GO exposure suppressed the survival of long-lived fat-5(tm420) mutants, whereas it increased the survival of short-lived nhr-49(nr2041) mutants. Hence, our studies collectively indicated that GO accumulation in reproductive organs, suppression of spermatogenesis, and the alteration of fatty acid metabolism play critical roles in understanding mechanisms of toxicity in C. elegans.


Assuntos
Caenorhabditis elegans/metabolismo , Ácidos Graxos/metabolismo , Grafite/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , Nanopartículas/toxicidade , Espermatogênese/efeitos dos fármacos , Animais , Feminino , Gônadas/efeitos dos fármacos , Gônadas/patologia , Intestinos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Longevidade/efeitos dos fármacos , Masculino , Mutação , Espécies Reativas de Oxigênio/metabolismo , Reprodução/efeitos dos fármacos , Contagem de Espermatozoides
15.
Hum Mol Genet ; 27(22): 3911-3918, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30085085

RESUMO

Whole-exome or whole-genome sequencing is becoming routine in clinical situations for identifying mutations underlying presumed genetic causes of disease including infertility. While this is a powerful approach for implicating polymorphisms or de novo mutations in genes plausibly related to the phenotype, a greater challenge is to definitively prove causality. This is a crucial requisite for treatment, especially for infertility, in which validation options are limited. In this study, we created a mouse model of a putative infertility allele, DMC1M200V. DMC1 encodes a RecA homolog essential for meiotic recombination and fertility in mice. This allele was originally implicated as being responsible for the sterility of a homozygous African woman, a conclusion supported by subsequent biochemical analyses of the mutant protein and by studies of yeast with the orthologous amino acid change. Here, we found that Dmc1M200V/M200V male and female mice are fully fertile and do not exhibit any gonadal abnormalities. Detailed immunocytological analysis of meiosis revealed no defects suggestive of compromised fertility. This study serves as a cautionary tale for making conclusions about consequences of genetic variants, especially with respect to infertility, and emphasizes the importance of conducting relevant biological assays for making accurate diagnoses in the era of genomic medicine.


Assuntos
Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Infertilidade/genética , Meiose/genética , Proteínas Nucleares/genética , Alelos , Animais , Modelos Animais de Doenças , Feminino , Gônadas/crescimento & desenvolvimento , Gônadas/patologia , Humanos , Infertilidade/fisiopatologia , Masculino , Camundongos , Mutação , Proteínas de Ligação a Fosfato , Recombinases , Recombinação Genética
16.
J Clin Endocrinol Metab ; 103(10): 3706-3713, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30053001

RESUMO

Background: Feminizing adrenocortical carcinoma (ACC) is rare. The source of estrogen production and the underlying mechanism remain unclear. Objective: In the current study, we investigated the source and the molecular mechanism of estrogen production in feminizing ACC. Methods: A total of 46 consecutive patients with a diagnosis of ACC were recruited in our center. We described the clinical characteristics and steroid hormone profile of the peripheral and adrenal vein. In both feminizing ACC tissues and cell lines, we investigated the expression of steroidogenic biomarkers and ß-catenin pathways by quantitative PCR and immunohistochemical staining. The effects of Wnt inhibitors on steroidogenesis were also analyzed in NCI-H295R cells. Results: A total of 46 consecutive patients with ACC were analyzed, and 25 had functional ACC. Four patients received a diagnosis of feminizing ACC based on feminizing manifestations, high levels of estradiol that were normalized after surgery, and histological Weiss score. Gonadal steroidogenic biomarkers including CYP19A1, HSD17B3, and LHCGR were markedly elevated in the feminizing ACC tissues. Adrenal vein sampling and liquid chromatography-tandem mass spectrometry suggested high CYP19A1 activity in the adrenal mass. ß-catenin expression was also elevated. When treated with niclosamide and PNU-74654, the H295R cell line showed a decrease in ß-catenin expression, cell proliferation, and steroid secretion. All steroid hormone enzymes were inhibited, whereas CYP19A1, HSD17B3, and LHCGR mRNA increased. Conclusions: Feminizing ACC can express high levels of CYP19A1, thus ectopically producing estrogens. Wnt pathway activation and dedifferentiation toward common adrenal-gonadal precursor cells may be the underlying mechanisms.


Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Desdiferenciação Celular , Estrogênios/metabolismo , Feminização , Hormônios Esteroides Gonadais/metabolismo , Gônadas/patologia , Neoplasias do Córtex Suprarrenal/metabolismo , Carcinoma Adrenocortical/metabolismo , Adulto , Apoptose , Biomarcadores/análise , Proliferação de Células , Feminino , Seguimentos , Gônadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Células Tumorais Cultivadas , Via de Sinalização Wnt
17.
Aquat Toxicol ; 202: 188-195, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30056249

RESUMO

Our previous observations proposed Pelophylax nigromaculatus as a model species for studying the masculinizing effects of androgenic EDCs in amphibians. To better develop this model species, we studied the process of the gonadal differentiation/development and the sensitive stage to androgens. We found that the earliest sexual dimorphism in gonads at morphological and histological levels occurred at stages 38-40 and stage 36 respectively. Further examination of molecular markers for testicular and ovarian differentiation during development revealed that the cyp17 and cyp19 expressions were sexually dimorphic from stage 32 and stage 36 respectively. Further, we investigated the sex-reversal induced by 100 ng/L 5α-dihydrotestosterone (DHT) when exposures were initiated at stages 24, 26 and 28. We found that when exposed from stage 24, DHT resulted masculinization of all tadpoles with no typical ovaries, whereas exposures from stage 26 or 28 dramatically reduced the effect of DHT. Our findings show that gonads of P. nigromaculatus are bipotential at stage 24, in the process of differentiation at stage 26 and determined to become either testis or ovary at stage 28. Altogether, exposure of P. nigromaculatus should begin at stage 24 in order to sensitively detect masculinizing effects of EDCs. Present study provides useful information about the gonadal differentiation and development in P. nigromaculatus for effectively evaluating masculinizing effects of EDCs on gonads.


Assuntos
Di-Hidrotestosterona/toxicidade , Disruptores Endócrinos/toxicidade , Gônadas/efeitos dos fármacos , Ranidae/crescimento & desenvolvimento , Diferenciação Sexual/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Aromatase/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Gônadas/metabolismo , Gônadas/patologia , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Larva/metabolismo , Masculino , Ranidae/metabolismo , Esteroide 17-alfa-Hidroxilase/metabolismo
18.
Sex Dev ; 12(4): 191-195, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29886504

RESUMO

Identification of novel genes involved in sexual development is crucial for understanding disorders of sex development (DSD). Here, we propose a member of the START domain family, the X chromosome STARD8, as a DSD candidate gene. We have identified a missense mutation of this gene in 2 sisters with 46,XY gonadal dysgenesis, inherited from their heterozygous mother. Gonadal tissue of one of the sisters contained Leydig cells overloaded with cholesterol droplets, i.e., structures previously identified in 46,XY DSD patients carrying mutations in the STAR gene encoding another START domain family member, which is crucial for steroidogenesis. Based on the phenotypes of our patients, we propose a dual role of STARD8 in sexual development, namely in testes determination and testosterone synthesis. However, further studies are needed to confirm the involvement of STARD8 in sexual development.


Assuntos
Cromossomos Humanos X/genética , Proteínas Ativadoras de GTPase/genética , Disgenesia Gonadal 46 XY/genética , Mutação/genética , Processos de Determinação Sexual/genética , Irmãos , Adolescente , Sequência de Bases , Feminino , Gônadas/patologia , Humanos , Lactente , Fenótipo
19.
Sex Dev ; 12(4): 175-179, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29879705

RESUMO

Some patients with mixed gonadal dysgenesis (MGD), whose prototypical karyotype is 45,X/46,XY, are known to manifest complications characteristic of Turner syndrome. We report a 16-year-old social male with MGD presenting with coarctation of the aorta, one of the common complications for Turner syndrome. At birth, the patient was found to have hypospadias, bifid scrotum, and cryptorchidism. Chromosomal analysis of his lymphocytes revealed the karyotype 45,X[7]/46,X,dic(Y;22)(p11.3;q13.3)[23] (named 45,X/46,X+Y fragment in this article). A left gonadectomy was performed at 1 year of age, and the histology showed a streak gonad with an epithelial cord-like structure compatible with MGD. At the age of 10 years, coarctation of the aorta was discovered by chance, for which the patient underwent surgical repair. The ratio of mosaicism in the gonad and aortic tissues was estimated by FISH with probes to identify the X centromere-specific repeat sequence and Yp11.2. The mosaicism ratio of 45,X/46,X+Y fragment varied among the tissues, with those having a higher ratio being more likely to exhibit the Turner syndrome phenotype. Some 90% of cells in the aortic tissues and 80% in the gonadal tissues lacked a Y chromosome. In conclusion, the mosaicism ratio in the different tissues may explain the phenotypes in MGD.


Assuntos
Disgenesia Gonadal Mista/patologia , Mosaicismo , Síndrome de Turner/patologia , Adolescente , Aorta/patologia , Criança , Pré-Escolar , Gônadas/patologia , Gônadas/cirurgia , Humanos , Lactente , Recém-Nascido , Masculino , Ductos Paramesonéfricos/patologia , Fenótipo
20.
J Dev Orig Health Dis ; 9(5): 519-529, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29909796

RESUMO

The aim of the present work was to address experimentally the possible impact of exposure to air pollution during gestation on the differentiation and function of the gonads of the offspring using a rabbit model. Rabbits were exposed daily to diluted diesel exhaust gas or filtered air from the 3rd until the 27th day of gestation, during which time germ cells migrate in genital ridges and divide, and fetal sex is determined. Offspring gonads were collected shortly before birth (28th day of gestation) or after puberty (7.5 months after birth). The structure of the gonads was analyzed by histological and immunohistological methods. Serum concentrations of testosterone and anti-Müllerian hormone were determined using ELISA. The morphology and the endocrine function of the gonads collected just at the arrest of the exposure were similar in polluted and control animals in both sexes. No differences were observed as well in gonads collected after puberty. Sperm was collected at the head of the epididymis in adults. Sperm motility and DNA fragmentation were measured. Among all parameters analyzed, only the sperm DNA fragmentation rate was increased three-fold in exposed males. Mechanisms responsible for these modifications and their physiological consequences are to be further clarified.


Assuntos
Desenvolvimento Fetal/efeitos dos fármacos , Gônadas/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Emissões de Veículos/toxicidade , Animais , Hormônio Antimülleriano/sangue , Fragmentação do DNA/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Feminino , Gônadas/embriologia , Gônadas/patologia , Masculino , Ovário/efeitos dos fármacos , Ovário/patologia , Gravidez , Coelhos , Motilidade Espermática/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/patologia , Testosterona/sangue
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