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1.
Chemosphere ; 237: 124414, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31352099

RESUMO

Chemicals are present in combination in ambient water, however toxicities of their mixtures are not well understood. This study investigated the effects of ketoconazole (KCZ) on the responses induced by bisphenol A (BPA) in zebrafish and in human adrenocarcinoma (H295R) cells. After exposure to BPA alone or mixed with KCZ for 21 d, egg production, relative tissue weights, sex hormone levels, cytochrome P450 (CYP)3a activity, and transcriptions of genes related to CYP metabolism, vitellogenesis, and steroidogenesis were determined in zebrafish. Male fish were more sensitive to the adverse effects of BPA than females, and the presence of KCZ potentiated the BPA-induced estrogenic responses in the male and anti-estrogenic responses in the female fish. In male zebrafish exposed to BPA, a significant reduction in egg number and relative gonad weight, an increase in 17ß-estradiol (E2) to testosterone (T) ratio, and an upregulation of vtg, erα, and cyp19a genes were observed. Under KCZ, BPA exposure resulted in a significant downregulation of cyp3a65 and pxr genes and an increase in estrogenic responses in males. In female fish, anti-estrogenic effects, such as a decrease in E2 concentration, were observed following the combined exposure. These results indicate that KCZ could increase the toxicity of the chemicals that depend on the given CYP metabolism for their elimination or other crucial functions such as steroidogenesis. Co-exposure to BPA and KCZ in H295R cells also increased E2 and decreased T production. Release and presence of this azole compound warrant caution, because it could modify adverse effects of BPA.


Assuntos
Compostos Benzidrílicos/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Cetoconazol/toxicidade , Fenóis/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Linhagem Celular Tumoral , Sistema Enzimático do Citocromo P-450/genética , Disruptores Endócrinos/toxicidade , Estradiol/metabolismo , Antagonistas de Estrogênios/toxicidade , Estrogênios/toxicidade , Feminino , Humanos , Masculino , Óvulo/efeitos dos fármacos , Óvulo/patologia , Testosterona/metabolismo , Testes de Toxicidade , Vitelogeninas/genética
3.
Emerg Infect Dis ; 24(8): 1407-1411, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30014830

RESUMO

Occasionally, abnormal forms of parasitic helminth eggs are detected during routine diagnostics. This finding can prove problematic in diagnosis because morphologic analysis based on tightly defined measurements is the primary method used to identify the infecting species and molecular confirmation of species is not always feasible. We describe instances of malformed nematode eggs (primarily from members of the superfamily Ascaridoidea) from human clinical practice and experimental trials on animals. On the basis of our observations and historical literature, we propose that unusual development and morphology of nematode and trematode eggs are associated with early infection. Further observational studies and experimentation are needed to identify additional factors that might cause abnormalities in egg morphology and production. Abnormal egg morphology can be observed early in the course of infection and can confound accurate diagnosis of intestinal helminthiases.


Assuntos
Helmintíase/parasitologia , Enteropatias Parasitárias/parasitologia , Nematoides/isolamento & purificação , Óvulo/patologia , Trematódeos/isolamento & purificação , Animais , Humanos , Óvulo/crescimento & desenvolvimento
4.
Nutrients ; 10(7)2018 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-29954124

RESUMO

Sperm cells are highly sensitive to reactive oxygen species (ROS), which are produced during cellular oxidation. In normal cell biology, ROS levels increase with a decreasing antioxidant response, resulting in oxidative stress which threatens sperm biology. Oxidative stress has numerous effects, including increased apoptosis, reduced motion parameters, and reduced sperm integrity. In this regard, green tea polyphenols (GrTPs) have been reported to possess properties that may increase the quality of male and female gametes, mostly via the capability of catechins to reduce ROS production. GrTPs have antioxidant properties that improve major semen parameters, such as sperm concentration, motility, morphology, DNA damage, fertility rate, and gamete quality. These unique properties of green tea catechins could improve reproductive health and represent an important study area. This exploratory review discusses the therapeutic effects of GrTPs against infertility, their possible mechanisms of action, and recommended supportive therapy for improving fertility in humans and in animals.


Assuntos
Antioxidantes/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Fármacos para a Fertilidade Masculina/uso terapêutico , Fertilidade/efeitos dos fármacos , Infertilidade Feminina/tratamento farmacológico , Infertilidade Masculina/tratamento farmacológico , Polifenóis/uso terapêutico , Saúde Reprodutiva , Chá , Animais , Antioxidantes/isolamento & purificação , Feminino , Humanos , Infertilidade Feminina/metabolismo , Infertilidade Feminina/patologia , Infertilidade Feminina/fisiopatologia , Infertilidade Masculina/metabolismo , Infertilidade Masculina/patologia , Infertilidade Masculina/fisiopatologia , Masculino , Óvulo/efeitos dos fármacos , Óvulo/metabolismo , Óvulo/patologia , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/isolamento & purificação , Gravidez , Fatores de Risco , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologia , Chá/química
5.
Obstet Gynecol Clin North Am ; 45(1): 113-125, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29428279

RESUMO

Preimplantation genetic testing encompasses preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD). PGS improves success rates of in vitro fertilization by ensuring the transfer of euploid embryos that have a higher chance of implantation and resulting in a live birth. PGD enables the identification of embryos with specific disease-causing mutations and transfer of unaffected embryos. The development of whole genome amplification and genomic tools, including single nucleotide polymorphism microarrays, comparative genomic hybridization microarrays, and next-generation sequencing, has led to faster, more accurate diagnoses that translate to improved pregnancy and live birth rates.


Assuntos
Doenças Genéticas Inatas/diagnóstico , Testes Genéticos/métodos , Diagnóstico Pré-Implantação , Biópsia , Blastocisto/patologia , Blastocisto/fisiologia , Blastômeros/patologia , Análise Citogenética , Feminino , Doenças Genéticas Inatas/genética , Testes Genéticos/ética , Humanos , Óvulo/patologia , Gravidez , Taxa de Gravidez , Diagnóstico Pré-Implantação/ética , Diagnóstico Pré-Implantação/métodos , Técnicas de Reprodução Assistida
6.
Fertil Steril ; 109(1): 39-43, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29307398

RESUMO

Tumor protein 53 (TP53) and its related family of p63 and p73 are tumor suppressor genes that regulate cellular activity to enhance longevity. p53 binds to specific response elements in DNA, modulating the transcription of genes that govern the major defenses against tumor growth. Additional members of the p53 family are involved with male and female germ cell survival. Although the majority of studies have focused on p53 as a tumor suppressor gene, little is known about its function in normal cellular processes. Polymorphisms of TP53 codon 72 that alter activity levels have been studied with respect to implantation in both the murine and human models. TP53 codon 72 (arginine) exhibits higher rates of apoptosis and leukemia inhibitory factor expression, whereas the C allele (proline) reduces leukemia inhibitory factor expression. Here, we review the role of p53 and the family of p53 proteins, along with the potential effect of p53 polymorphisms on reproduction.


Assuntos
Fertilidade , Infertilidade/metabolismo , Óvulo/metabolismo , Espermatozoides/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Aborto Espontâneo/genética , Aborto Espontâneo/metabolismo , Aborto Espontâneo/fisiopatologia , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Feminino , Fertilidade/genética , Fertilização In Vitro , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Infertilidade/genética , Infertilidade/fisiopatologia , Infertilidade/terapia , Fator Inibidor de Leucemia/genética , Fator Inibidor de Leucemia/metabolismo , Masculino , Óvulo/patologia , Polimorfismo Genético , Transdução de Sinais , Espermatozoides/patologia , Proteína Supressora de Tumor p53/genética
7.
Biomed Pharmacother ; 96: 64-71, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28965009

RESUMO

This paper is the first report on the in vitro effects of licochalcone A, a chalcone isolated from Glycyrrhiza inflate Batalin (Leguminosae), on Schistosoma mansoni adult worms. In vitro, licochalcone A afforded lethal concentrations for 50% of parasites (LC50) of 9.12±1.1 and 9.52±0.9µM against female and male adult worms, respectively, at 24h. Additionally, the compound reduced the total number of S. mansoni eggs and affected the development of eggs produced by S. mansoni adult worms. Together, the results achieved after 24h showed that licochalcone A was 55.7- and 53.3-fold more toxic to S. mansoni female and male adult worms than to Chinese hamster ovary fibroblasts cells, respectively. Treatment with licochalcone A elicited drastic changes in the tegument of S. mansoni adult worms, as well as mitochondrial alteration and chromatin condensation. Licochalcone A also increased the superoxide anion level and decreased the superoxide dismutase activity in S. mansoni adult worms. Overall, our results indicated that licochalcone A displays in vitro schistosomicidal activity. This effect may result from increased production of reactive oxygen species (ROS) induced by the action of licochalcone A. The resulting ROS could act on the S. mansoni tegument and membranes and help induce the death of S. mansoni adult worms.


Assuntos
Chalconas/farmacologia , Glycyrrhiza , Extratos Vegetais/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Schistosoma mansoni/metabolismo , Fatores Etários , Animais , Relação Dose-Resposta a Droga , Feminino , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óvulo/efeitos dos fármacos , Óvulo/metabolismo , Óvulo/patologia , Extratos Vegetais/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo , Schistosoma mansoni/citologia , Caramujos
8.
Toxicol Appl Pharmacol ; 329: 9-17, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28552778

RESUMO

Zearalenone (ZEA) is a mycotoxin produced by fusarium graminearum. It can cause abnormal reproductive function by acting as an environmental estrogen. Research has traditionally focused on acute and chronic injury on mammalian reproductive capacity after ZEA treatment. Little research has been done studying the effects of ZEA exposure on early oogenesis. In this study, we investigate the effects of ZEA exposure on meiotic entry, DNA double-strand breaks (DSBs), and primordial follicle assembly during murine early oogenesis. The results show that ZEA exposure significantly decreased the percentage of diplotene stage germ cells, and made more germ cells remain at zygotene or pachytene stages. Moreover, the mRNA expression level of meiosis-related genes was significantly reduced after ZEA treatment. ZEA exposure significantly increased DNA-DSBs at the diplotene stage. Meanwhile, DNA damage repair genes such as RAD51 and BRCA1 were activated. Furthermore, maternal exposure to ZEA significantly decreased the number of primordial follicles in newborn mouse ovaries. In conclusion, ZEA exposure impairs mouse female germ cell meiotic progression, DNA-DSBs, and primordial follicle assembly.


Assuntos
Disruptores Endócrinos/toxicidade , Estrogênios não Esteroides/toxicidade , Meiose/efeitos dos fármacos , Oogênese/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Proteína BRCA1 , Quebras de DNA de Cadeia Dupla , Reparo do DNA/efeitos dos fármacos , Feminino , Prófase Meiótica I/efeitos dos fármacos , Camundongos , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Óvulo/metabolismo , Óvulo/patologia , Gravidez , Rad51 Recombinase/metabolismo , Medição de Risco , Proteínas Supressoras de Tumor/metabolismo
9.
Korean J Gastroenterol ; 69(4): 243-247, 2017 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28449427

RESUMO

Trichuris trichiura infection is a common helminth infection, which is transmitted via soil, with worldwide distribution, especially in rural areas of developing countries. Occasionally, sporadic cases occur in non-endemic, developed areas due to the widespread of immigration. We experienced a case of Trichuris dysentery syndrome in a young North Korean defector, who had been suffering from chronic abdominal pain for 10 years. He is relatively short and thin compared with his older brother. Unexpectedly, the diagnosis, made by a colonoscopy, revealed numerous, small, white, and gently moving worms at the cecum and ascending colon. After 3 days of albendazole (400 mg once daily) administration, clinical symptoms subsided dramatically. On the follow-up colonoscopy, which was performed two months after the completion of his treatment, complete eradication was identified. Soil-transmitted helminths, including Trichuris trichiura, are disappearing becoming less prevalent in South Korea as a result of both national driving force and environmental improvement. However, these diseases should be considered when we meet foreign patients from developing countries, like North Korea, presenting chronic abdominal pain. Moreover, proper treatment of North Korean defectors and performing cohort studies of them would help to prepare for the possible unification era in the field of gastroenterology.


Assuntos
Dor Abdominal/etiologia , Tricuríase/diagnóstico , Adulto , Animais , Ceco/parasitologia , Ceco/patologia , Colo/parasitologia , Colo/patologia , Colonoscopia , República Democrática Popular da Coreia , Disenteria/diagnóstico , Emigrantes e Imigrantes , Humanos , Masculino , Óvulo/patologia , Tricuríase/complicações , Tricuríase/parasitologia , Trichuris/crescimento & desenvolvimento , Trichuris/isolamento & purificação
10.
PLoS One ; 12(4): e0175646, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28410387

RESUMO

Parasitic infections are generally diagnosed by professionals trained to recognize the morphological characteristics of the eggs in microscopic images of fecal smears. However, this laboratory diagnosis requires medical specialists which are lacking in many of the areas where these infections are most prevalent. In response to this public health issue, we developed a software based on pattern recognition analysis from microscopi digital images of fecal smears, capable of automatically recognizing and diagnosing common human intestinal parasites. To this end, we selected 229, 124, 217, and 229 objects from microscopic images of fecal smears positive for Taenia sp., Trichuris trichiura, Diphyllobothrium latum, and Fasciola hepatica, respectively. Representative photographs were selected by a parasitologist. We then implemented our algorithm in the open source program SCILAB. The algorithm processes the image by first converting to gray-scale, then applies a fourteen step filtering process, and produces a skeletonized and tri-colored image. The features extracted fall into two general categories: geometric characteristics and brightness descriptions. Individual characteristics were quantified and evaluated with a logistic regression to model their ability to correctly identify each parasite separately. Subsequently, all algorithms were evaluated for false positive cross reactivity with the other parasites studied, excepting Taenia sp. which shares very few morphological characteristics with the others. The principal result showed that our algorithm reached sensitivities between 99.10%-100% and specificities between 98.13%- 98.38% to detect each parasite separately. We did not find any cross-positivity in the algorithms for the three parasites evaluated. In conclusion, the results demonstrated the capacity of our computer algorithm to automatically recognize and diagnose Taenia sp., Trichuris trichiura, Diphyllobothrium latum, and Fasciola hepatica with a high sensitivity and specificity.


Assuntos
Algoritmos , Helmintíase/diagnóstico , Animais , Difilobotríase/diagnóstico , Diphyllobothrium/crescimento & desenvolvimento , Fasciola hepatica/crescimento & desenvolvimento , Fasciolíase/diagnóstico , Humanos , Processamento de Imagem Assistida por Computador , Microscopia , Óvulo/patologia , Reconhecimento Automatizado de Padrão , Sensibilidade e Especificidade , Taenia/crescimento & desenvolvimento , Teníase/diagnóstico , Tricuríase/diagnóstico , Trichuris/crescimento & desenvolvimento
11.
J Assist Reprod Genet ; 33(9): 1169-74, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27262838

RESUMO

PURPOSE: The purpose of our study was to determine if progesterone (P4) values on day of trigger affect certain cycle outcome parameters, ploidy status of embryos, as well as pregnancy outcomes in the subsequent first frozen embryo transfer cycle. METHODS: Two hundred thirty-eight patients undergoing pre-gestational screening and freeze all protocol at our fertility center from 2013 to 2014 were included. Excluded patients were those whom had cancelled cycles prior to egg retrieval as well as cycles utilizing donor eggs. Once patients were identified as eligible for this study, frozen serum from the day of trigger was identified and analyzed using the Siemens Immulite 2000. Number of eggs retrieved, number of available embryos for biopsy, and number of euploid/aneuploid embryos were analyzed. The first frozen embryo transfer cycle was linked to the initial egg retrieval and outcomes including pregnancy rates, and live birth/ongoing pregnancy rates were calculated and analyzed. A discriminatory P4 value of 1.5 ng/ml was set. Group A had P4 values of less than 1.5 ng/ml and group B had P4 values greater than or equal to 1.5 ng/ml. T tests and chi-squared tests were used for statistical analysis. RESULTS: Group A had an average trigger P4 value of 0.87 +/- 0.3 and group B had an average trigger P4 of 2.1 +/- 0.8. Table 1 shows the baseline characteristics of both group A and group B. The only significant difference between the two groups was total gonadotropin dosage (IU) with a p value of 0.02 and estradiol (pg/ml) at trigger, also with a p value of 0.02 (Table 1). Number of eggs retrieved, number of embryos biopsied, number euploid/aneuploid, and non-diagnosis embryos were all non-significant. Chi-square analysis was used to compare pregnancy rates between the two groups after the first frozen embryo transfer cycle. Group A had a pregnancy rate of 72 % and Group B had a pregnancy rate of 66.7 %, which was not significant. Ongoing pregnancy/live birth rates were 65.6 % in group A and 66.67 % in group B, also not significant (Table 2). CONCLUSIONS: P4 values on day of trigger do not affect number of eggs retrieved and number of chromosomally normal embryos available for transfer in a subsequent embryo transfer cycle. Elevated P4 values (≥1.5 ng/ml) also do not affect pregnancy rates or live birth/ongoing pregnancy rates in the first subsequent frozen embryo transfer cycle.


Assuntos
Transferência Embrionária , Indução da Ovulação/métodos , Óvulo/crescimento & desenvolvimento , Progesterona/sangue , Adulto , Coeficiente de Natalidade , Endométrio/metabolismo , Endométrio/patologia , Feminino , Fertilidade , Fertilização In Vitro/métodos , Humanos , Óvulo/patologia , Ploidias , Gravidez , Taxa de Gravidez
12.
J Genet ; 95(2): 297-302, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27350672

RESUMO

A striking infertile phenotype has been discovered in the DDK strain of mouse. The DDK females are usually infertile when crossed with males of other inbred strains, whereas DDK males exhibit normal fertility in reciprocal crosses. This phenomenon is caused by mutation in the ovum (Om) locus on chromosome 11 and known as the DDK syndrome. Previously, some research groups reported that the embryonic mortality deviated from the semilethal rate in backcrosses between heterozygous (Om/+) females and males of other strains. This embryonic mortality exhibited an aggravated trend with increasing background genes of other strains. These results indicated that some modifier genes of Om were present in other strains. In the present study, a population of N22 (Om/+) females from the backcrosses between C57BL/6J (B6) and F1 (B6♀ × DDK♂) was used to map potential modifier genes of Om. Quantitative trait locus showed that a major locus, namely Amom1 (aggravate modifier gene of Om 1), was located at the middle part of chromosome 9 in mice. The Amom1 could increase the expressivity of Om gene, thereby aggravating embryonic lethality when heterozygous (Om/+) females mated with males of B6 strain. Further, the 1.5 LOD-drop analysis indicated that the confidence interval was between 37.54 and 44.46 cM, ~6.92 cM. Amom1 is the first modifier gene of Om in the B6 background.


Assuntos
Cromossomos de Mamíferos/química , Genes Letais , Genes Modificadores , Infertilidade Feminina/genética , Locos de Características Quantitativas , Animais , Mapeamento Cromossômico , Cruzamentos Genéticos , Embrião de Mamíferos , Feminino , Heterozigoto , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Mutação , Óvulo/metabolismo , Óvulo/patologia , Fenótipo
13.
Mol Hum Reprod ; 22(6): 397-409, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26921397

RESUMO

STUDY HYPOTHESIS: Cellular aging of the egg following ovulation, also known as post-ovulatory aging, is associated with aberrant cortical mechanics and actomyosin cytoskeleton functions. STUDY FINDING: Post-ovulatory aging is associated with dysfunction of non-muscle myosin-II, and pharmacologically induced myosin-II dysfunction produces some of the same deficiencies observed in aged eggs. WHAT IS KNOWN ALREADY: Reproductive success is reduced with delayed fertilization and when copulation or insemination occurs at increased times after ovulation. Post-ovulatory aged eggs have several abnormalities in the plasma membrane and cortex, including reduced egg membrane receptivity to sperm, aberrant sperm-induced cortical remodeling and formation of fertilization cones at the site of sperm entry, and reduced ability to establish a membrane block to prevent polyspermic fertilization. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Ovulated mouse eggs were collected at 21-22 h post-human chorionic gonadotrophin (hCG) (aged eggs) or at 13-14 h post-hCG (young eggs), or young eggs were treated with the myosin light chain kinase (MLCK) inhibitor ML-7, to test the hypothesis that disruption of myosin-II function could mimic some of the effects of post-ovulatory aging. Eggs were subjected to various analyses. Cytoskeletal proteins in eggs and parthenogenesis were assessed using fluorescence microscopy, with further analysis of cytoskeletal proteins in immunoblotting experiments. Cortical tension was measured through micropipette aspiration assays. Egg membrane receptivity to sperm was assessed in in vitro fertilization (IVF) assays. Membrane topography was examined by low-vacuum scanning electron microscopy (SEM). MAIN RESULTS AND THE ROLE OF CHANCE: Aged eggs have decreased levels and abnormal localizations of phosphorylated myosin-II regulatory light chain (pMRLC; P = 0.0062). Cortical tension, which is mediated in part by myosin-II, is reduced in aged mouse eggs when compared with young eggs, by ∼40% in the cortical region where the metaphase II spindle is sequestered and by ∼50% in the domain to which sperm bind and fuse (P < 0.0001). Aging-associated parthenogenesis is partly rescued by treating eggs with a zinc ionophore (P = 0.003), as is parthenogenesis induced by inhibition of mitogen-activated kinase (MAPK) 3/1 [also known as extracellular signal-regulated kinase (ERK)1/2] or MLCK. Inhibition of MLCK with ML-7 also results in effects that mimic those of post-ovulatory aging: fertilized ML-7-treated eggs show both impaired fertilization and increased extents of polyspermy, and ML-7-treated young eggs have several membrane abnormalities that are shared by post-ovulatory aged eggs. LIMITATIONS, REASONS FOR CAUTION: These studies were done with mouse oocytes, and it remains to be fully determined how these findings from mouse oocytes would compare with other species. For studies using methods not amenable to analysis of large sample sizes and data are limited to what images one can capture (e.g. SEM), data should be interpreted conservatively. WIDER IMPLICATIONS OF THE FINDINGS: These data provide insights into causes of reproductive failures at later post-copulatory times. LARGE SCALE DATA: Not applicable. STUDY FUNDING AND COMPETING INTERESTS: This project was supported by R01 HD037696 and R01 HD045671 from the NIH to J.P.E. Cortical tension studies were supported by R01 GM66817 to D.N.R. The authors declare there are no financial conflicts of interest.


Assuntos
Senescência Celular/fisiologia , Óvulo/metabolismo , Animais , Azepinas/farmacologia , Senescência Celular/genética , Citoesqueleto/metabolismo , Feminino , Masculino , Camundongos , Microscopia de Fluorescência , Miosina Tipo II/metabolismo , Naftalenos/farmacologia , Oócitos/citologia , Oócitos/metabolismo , Ovulação/genética , Ovulação/fisiologia , Óvulo/efeitos dos fármacos , Óvulo/patologia , Interações Espermatozoide-Óvulo/genética , Interações Espermatozoide-Óvulo/fisiologia , Espermatozoides/citologia , Espermatozoides/metabolismo
14.
J Clin Invest ; 125(11): 4295-304, 2015 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-26485283

RESUMO

Ovarian development and maintenance are poorly understood; however, diseases that affect these processes can offer insights into the underlying mechanisms. XX female gonadal dysgenesis (XX-GD) is a rare, genetically heterogeneous disorder that is characterized by underdeveloped, dysfunctional ovaries, with subsequent lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism. Here, we report an extended consanguineous family of Palestinian origin, in which 4 females exhibited XX-GD. Using homozygosity mapping and whole-exome sequencing, we identified a recessive missense mutation in nucleoporin-107 (NUP107, c.1339G>A, p.D447N). This mutation segregated with the XX-GD phenotype and was not present in available databases or in 150 healthy ethnically matched controls. NUP107 is a component of the nuclear pore complex, and the NUP107-associated protein SEH1 is required for oogenesis in Drosophila. In Drosophila, Nup107 knockdown in somatic gonadal cells resulted in female sterility, whereas males were fully fertile. Transgenic rescue of Drosophila females bearing the Nup107D364N mutation, which corresponds to the human NUP107 (p.D447N), resulted in almost complete sterility, with a marked reduction in progeny, morphologically aberrant eggshells, and disintegrating egg chambers, indicating defective oogenesis. These results indicate a pivotal role for NUP107 in ovarian development and suggest that nucleoporin defects may play a role in milder and more common conditions such as premature ovarian failure.


Assuntos
Aquaporinas/fisiologia , Proteínas de Drosophila/fisiologia , Disgenesia Gonadal 46 XX/genética , Mutação de Sentido Incorreto , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Ovário/patologia , Adolescente , Adulto , Animais , Animais Geneticamente Modificados , Aquaporinas/deficiência , Aquaporinas/genética , Consanguinidade , Modelos Animais de Doenças , Proteínas de Drosophila/deficiência , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Feminino , Humanos , Infertilidade Feminina/genética , Masculino , Camundongos , Modelos Moleculares , Morfogênese , Complexos Multiproteicos , Complexo de Proteínas Formadoras de Poros Nucleares/deficiência , Complexo de Proteínas Formadoras de Poros Nucleares/fisiologia , Oogênese/genética , Óvulo/patologia , Linhagem , Conformação Proteica
15.
J Appl Toxicol ; 35(1): 11-3, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25580481

RESUMO

The most potent chemicals potentially causing adverse effects on fish species are estrogens in human waste.Sewage is a source of these estrogens and it is difficult to reduce. In particular, although the bioactivity of estrone is estimated to be about half of that of estradiol, multiple studies report that more than 100 ng l(­1) of estrone can be detected in urban rivers, including discharges from sewage treatment works; approximately two times as high as estradiol. Few studies have been conducted to investigate the long-term effects of estrone on wildlife; therefore, we conducted fish multigeneration test using Japanese medaka (Oryzias latipes). Medaka were exposed to estrone for 27 weeks across three generations in environmentally relevant concentrations, being 5.74, 11.4, 24.0, 47.1 and 91.4 ng l(­1). No effects on reproduction were observed in the first generation; however, a decline in egg production and fertility was observed in the second generation exposed to 91.4 ng l(­1) estrone, which is lower than some known environmental concentrations in urban environments. Furthermore, histopathological abnormalities were observed in the third generation exposed to both 47.1 and 91.4 ng l(­1), suggesting that estrone possibly exerts severe effects on the third or later generations. However, appearances of testis­ova were observed in the second and third generation they were not consistent with actual effects on reproduction, notwithstanding the testis-ovais regarded as the key evidence for endocrine disruption. Accordingly, we consider that qualitative measurement of abnormalities using histopathological observations is required for appropriate evaluation of endocrine disruption.


Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Estrona/toxicidade , Reprodução/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Anormalidades Induzidas por Medicamentos/etiologia , Anormalidades Induzidas por Medicamentos/patologia , Animais , Relação Dose-Resposta a Droga , Feminino , Masculino , Oryzias , Óvulo/efeitos dos fármacos , Óvulo/patologia , Testículo/efeitos dos fármacos , Testículo/embriologia , Testículo/patologia , Fatores de Tempo , Testes de Toxicidade
16.
Cell Death Dis ; 6: e1589, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25590799

RESUMO

Primary ovarian insufficiency (POI) is a common cause of infertility in around 1-2% of women aged <40 years. However, the mechanisms that cause POI are still poorly understood. Here we showed that germ cell-specific knockout of an essential autophagy induction gene Atg7 led to subfertility in female mice. The subfertility of Atg7 deletion females was caused by severe ovarian follicle loss, which is very similar to human POI patients. Further investigation revealed that germ cell-specific Atg7 knockout resulted in germ cell over-loss at the neonatal transition period. In addition, our in vitro studies also demonstrated that autophagy could protect oocytes from over-loss by apoptosis in neonatal ovaries under the starvation condition. Taken together, our results uncover a new role for autophagy in the regulation of ovarian primordial follicle reservation and hint that autophagy-related genes might be potential pathogenic genes to POI of women.


Assuntos
Proteínas Associadas aos Microtúbulos/deficiência , Óvulo/metabolismo , Insuficiência Ovariana Primária/metabolismo , Insuficiência Ovariana Primária/patologia , Animais , Animais Recém-Nascidos , Apoptose , Autofagia , Proteína 7 Relacionada à Autofagia , Contagem de Células , Feminino , Feto/patologia , Deleção de Genes , Humanos , Infertilidade Feminina/metabolismo , Infertilidade Feminina/patologia , Camundongos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/metabolismo , Oócitos/metabolismo , Oócitos/patologia , Especificidade de Órgãos , Folículo Ovariano/embriologia , Folículo Ovariano/patologia , Óvulo/patologia
17.
Mol Cell Endocrinol ; 399: 250-8, 2015 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-25458700

RESUMO

Vitelline membrane outer layer protein 1 (VMO1), a basic protein present in the outer layer of the vitelline membrane of eggs, plays essential roles in separating the yolk from the egg white and preventing infection from bacteria by forming a barrier of fibrous layers in avian eggs. Although VMO1 is expressed in the oviduct of hens, little is known about endocrine regulation of transcription of VMO1 in the oviduct and its expression in cancerous ovaries of laying hens. Results of present study indicated that expression of VMO1 mRNA increased in the chick oviduct in response to diethylstilbestrol (DES, a synthetic non-steroidal estrogen). VMO1 mRNA and protein were particularly abundant in the glandular epithelium (GE) and luminal epithelium (LE) of the magnum of the oviducts of chicks treated with DES. Also, during the regression and recrudescence phases of the oviduct during induced molting with zinc feeding, VMO1 expression decreased as the oviduct regressed and increased with remodeling and recrudescence of the oviduct in laying hens. In addition, changes in relative expression of specific microRNAs (miR-1623, miR-1552-3p, miR-1573, miR-22-3p, miR-124a and miR-1764) regulating VMO1 gene were detected in the oviducts during the molting period. Moreover, abundant expression of VMO1 was found in GE of cancerous, but not normal ovaries of laying hens. Results of the present study suggest that VMO1 is regulated by estrogen and target microRNAs in the chicken oviduct and that it is a potential diagnostic marker of ovarian cancer in laying hens.


Assuntos
Biomarcadores Tumorais/biossíntese , Galinhas/metabolismo , Estrogênios/metabolismo , Proteínas de Membrana/biossíntese , Neoplasias Ovarianas , Oviductos/metabolismo , Óvulo/metabolismo , Doenças das Aves Domésticas , Animais , Feminino , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Proteínas de Neoplasias , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/veterinária , Oviductos/patologia , Óvulo/patologia , Doenças das Aves Domésticas/metabolismo , Doenças das Aves Domésticas/patologia , RNA Neoplásico/metabolismo
18.
Reprod Biol Endocrinol ; 12: 48, 2014 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-24885125

RESUMO

BACKGROUND: Current evidence about in-vivo effects of HPV cannot definitively clarify the possible negative role of this worldwide common infection in early embryo development. However in-vitro evidence, seems to underline a possible negative effect of HPV in increasing blastocyst apoptosis and in reducing the endometrial implantation of trophoblastic cells. On these bases we believe that a new scientific approach is necessary to better understand the real role of male and female HPV infection in infertility and early pregnancy development. METHODS: English literature review of manuscripts focused on HPV infection and human reproduction was conducted. We performed a critical analysis of evidence and possible bias affecting both in-vivo and in-vitro studies regarding this topic. RESULTS: The biggest limitation of the in-vivo studies is due to the inappropriate timing of HPV effects evaluation since evidence about in-vitro studies strongly suggests that a large part of HPV negative effects occurs during a very early stage of embryo development. All the efforts of the scientific community to investigate the real role of HPV in human reproduction disorders cannot underestimate the severe BIAS of actual evidence in postulating new hypothesis and research projects which are fundamental to clarify if HPV may be associated with unexplained couples infertility and early miscarriages. CONCLUSIONS: If the relationship between HPV gametes infection and early human reproduction step impairment will be confirmed, the HPV male and couple vaccination may represent a reliable option to improve fertility in some couples affected by infertility actually classified as "idiopathic" but maybe linked to HPV infection.


Assuntos
Alphapapillomavirus/patogenicidade , Embrião de Mamíferos/virologia , Desenvolvimento Embrionário , Infertilidade Feminina/etiologia , Infertilidade Masculina/etiologia , Infecções por Papillomavirus/fisiopatologia , Apoptose , Blastocisto/patologia , Blastocisto/virologia , Embrião de Mamíferos/patologia , Feminino , Humanos , Infertilidade Feminina/virologia , Infertilidade Masculina/virologia , Masculino , Óvulo/patologia , Óvulo/virologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Gravidez , Espermatozoides/patologia , Espermatozoides/virologia , Virulência
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