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1.
Ecotoxicol Environ Saf ; 205: 111338, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32956867

RESUMO

Lead (Pb) is well-recognized for its great hazards to human and wildlife health. It has negative influences on multiple organs and systems of birds. Especially, lead exposure caused adverse impacts on bird reproduction. In this study, one week old female Japanese quails were randomly allocated into four groups and each group was respectively fed with 0, 50 ppm, 500 ppm and 1000 ppm Pb in drinking water for 36 days to determine the effects of chronic lead exposure on ovarian development and function. The results showed that Pb did accumulate in the ovary and ovarian development was delayed by high dose lead exposure (500 ppm and 1000 ppm). Moreover, high Pb dosage induced ovarian histopathological damages characterized by granulosa cells disorganization, follicle atresia and interstitial cell degeneration. Meanwhile, the concentration of estradiol (E2) was significantly decreased and mRNA levels of genes involved with ovarian steroidogenesis were significantly down-regulated by high concentration Pb. In addition, Pb exposure caused increasing cell apoptosis and significant changes of the expression of genes involved with cell death in the ovary. High dose Pb exposure also inhibited thyroid hormone release and disrupted ovarian thyroid deiodination apart from causing thyroid histopathological injury such as follicular deformation and atrophy. The study indicated that Pb might cause ovarian malfunction by inducing ovary and thyroid microstructural damages, thyroid hormone and estrogen release inhibition and ovarian steroidogenesis disruption.


Assuntos
Coturnix/metabolismo , Poluentes Ambientais/toxicidade , Estradiol/metabolismo , Expressão Gênica/efeitos dos fármacos , Chumbo/toxicidade , Ovário/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , Adolescente , Animais , Apoptose/efeitos dos fármacos , Coturnix/genética , Coturnix/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Poluentes Ambientais/metabolismo , Estradiol/genética , Feminino , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/patologia , Humanos , Chumbo/metabolismo , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/patologia , Ovário/crescimento & desenvolvimento , Ovário/metabolismo , Ovário/patologia , Distribuição Aleatória , Reprodução/efeitos dos fármacos , Reprodução/genética , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Hormônios Tireóideos/genética
2.
Life Sci ; 249: 117515, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32147428

RESUMO

AIMS: This study investigated the effects of curcumin-loaded super-paramagnetic iron oxide (Fe3O4) nanoparticles (NPs) (SPIONs) on histological parameters and apoptosis-inducing factors (AIFs) in an experimental mouse model of polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: A total number of 40 female prepuberal BALB/c mice were randomly divided into four groups. Group 1 was selected as control and Group 2 was considered as a vehicle taking sesame oil, in the form of a curcumin carrier. Moreover, Group 3 was administered with dehydroepiandrosterone (DHEA) at 6 mg/100 g of the body weight and Group 4 received the DHEA plus the NPs of curcumin (5.4 mg/100 g) for twenty consecutive days. Finally, histology, stereology, and apoptosis of the ovary were evaluated. KEY FINDINGS: The results revealed that the NPs of curcumin had reduced ovarian volume (p < 0.05) and a total number of primary, secondary, antral, and primordial follicles in comparison with the PCOS and vehicle groups (p < 0.05). Furthermore, curcumin treatment following administration of the DHEA resulted in a significant decrease in BAX (p < 0.001) and levels of expression of Caspase3 (CASP3) protein, increased levels of B-cell lymphoma 2 (Bcl2) expression (p < 0.05), and moderated apoptosis in granulosa cells in comparison with the ones seen in the PCOS group. SIGNIFICANCE: Ovarian injuries and DHEA-induced apoptosis were efficiently suppressed by curcumin, indicating the probable protective property of NPs of curcumin against PCOS.


Assuntos
Apoptose/efeitos dos fármacos , Curcumina/administração & dosagem , Desidroepiandrosterona/administração & dosagem , Compostos Férricos/administração & dosagem , Nanopartículas Metálicas/química , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/tratamento farmacológico , Maturidade Sexual , Animais , Antioxidantes/administração & dosagem , Apoptose/genética , Caspase 3/metabolismo , Modelos Animais de Doenças , Feminino , Compostos Férricos/química , Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Estresse Oxidativo
3.
Int J Mol Med ; 45(2): 647-657, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894307

RESUMO

The molecular mechanisms underlying the activation of primordial follicles are poorly understood. The serine/threonine protein kinase phosphoinositide­dependent kinase 1 (PDK1), a pivotal downstream effector of phosphatidyl inositol­3 kinase (PI3K) signaling, plays a vital role in cellular signaling. In order to identify the function of PDK1 in ovarian follicle development, this study used conditional Pdk1 deletion in mouse oocytes by crossing Pdk1loxP/loxP mice with transgenic mice carrying Gdf­9 promoter­mediated Cre recombinase and found that Pdk1flx/flxGdf9Cre mice were subfertile with increased serum follicle­stimulating hormone (FSH) and luteinizing hormone (LH) levels compared with Pdk1flx/flx mice. The deletion of Pdk1 in oocytes induced massive primordial follicle activation, leading to premature ovarian failure (POF). Further investigation revealed that enhanced Yes­associated protein (YAP) expression and an increased pro­inflammatory response also contributed to massive primordial follicle activation. PDK1 formed the complex with the core kinases of Hippo signaling and regulated the expression levels of YAP. On the whole, the findings of the present study demonstrate that PDK1 serves as an indispensable gatekeeper for maintaining the primordial follicle pool and provide a deeper understanding of POF treatment.


Assuntos
Proteínas Quinases Dependentes de 3-Fosfoinositídeo/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Ciclo Celular/genética , Folículo Ovariano/metabolismo , Insuficiência Ovariana Primária/genética , Animais , Feminino , Deleção de Genes , Inflamação/genética , Inflamação/patologia , Camundongos Endogâmicos ICR , Oócitos/metabolismo , Folículo Ovariano/patologia , Insuficiência Ovariana Primária/patologia , Regulação para Cima
4.
Transplant Proc ; 52(1): 406-413, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31911055

RESUMO

BACKGROUND: Subcutaneous ovarian transplantation has recently begun receiving increased attention. Fourteen days after transplantation is used as an important time point for assessing the recovery of ovarian function. The goal of this study is to determine the expression of apoptotic genes in the ovary at this time. METHODS: This study investigated follicle development and the expression of 3 apoptosis genes (Bax, Bcl2, and P53) after mouse ovaries were transplanted. Seven-week-old mouse ovaries were autologously transplanted into back muscle. The ovaries were harvested on day 14, morphology was observed by hematoxylin and eosin staining, and the distribution of 3 proteins was observed by immunohistochemistry. TUNEL staining showed where apoptosis occurred in the ovary. Finally, RT-PCR/Western blotting was used to analyze the differential expression of mRNA/proteins between the transplantation group and the control group. RESULTS: The results revealed follicles at different stages at the edge of the grafts. In immunohistochemical experiments, BAX, BCL2, and P53 were found to be extensively expressed in the transplant group and the control group. P53 was strongly expressed in the medulla of transplanted ovaries. Bax was strongly expressed in the antral follicles of both groups. The results were consistent with the results of the TUNEL experiments. Three genes (Bax, Bcl2, and P53) were downregulated in the transplanted groups. The results showed that significant differences were detected in Bax and P53 mRNA expression levels between the transplanted groups and the control group (P < .01). Bcl2 expression was not significantly different, but the Bax/Bcl2 ratio increased. The results of the protein experiments were the same. CONCLUSION: P53 may downregulate Bax in the early stage of transplantation. Follicle growth and atresia were regulated through modulation of Bcl2- and Bax-mediated apoptotic pathways in heterotopic ovarian transplantation.


Assuntos
Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Ovário/metabolismo , Ovário/patologia , Ovário/transplante , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose/fisiologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Transplante Autólogo , Proteína X Associada a bcl-2/metabolismo
5.
Food Chem Toxicol ; 135: 110982, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31747621

RESUMO

With epidemic of obesity, it affects aspects of female reproduction. Genistein could ameliorate obesity in people and animals, but might exert adverse effects on the female reproductive system. To evaluate the effects of fetal and neonatal genistein exposure on the ovarian health of F1 obese female mice with obesity induced by high-fat diet after weaning, we simulated a diet-induced obesity model to observe and determine biological effects of genistein exposure on the ovarian follicle of overfed female mice. Results showed that F1 female mice with obesity induced by high-fat diet significantly prolonged the estrus cycle, disrupted sex hormonal balance and ovarian follicle development after they were exposed to 25 mg/kg b.w./day of genistein during the fetal and neonatal stages. Genistein significantly up-regulated the ovarian mRNA expression of estrogen receptor beta in F1 obese female mice, and high-fat diet influenced the ovarian mRNA expression of estrogen receptor alpha, luteinizing hormone receptor and follicle-stimulating hormone receptor. Hence, genistein exposure from the fetal stage might increase the risk of reproductive diseases in obese females in later life. Thus, the long-term risks of genistein to obese females should be thoroughly assessed.


Assuntos
Dieta Hiperlipídica , Genisteína/efeitos adversos , Obesidade/tratamento farmacológico , Folículo Ovariano/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Estradiol/metabolismo , Receptor beta de Estrogênio/genética , Ciclo Estral/efeitos dos fármacos , Feminino , Feto/efeitos dos fármacos , Hormônio Foliculoestimulante/metabolismo , Expressão Gênica/efeitos dos fármacos , Hormônio Luteinizante/metabolismo , Camundongos Endogâmicos ICR , Obesidade/metabolismo , Folículo Ovariano/embriologia , Folículo Ovariano/patologia , Gravidez , RNA Mensageiro/metabolismo
6.
Life Sci ; 239: 116999, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31654746

RESUMO

AIMS: The present study aimed to investigate the effects of cyclophosphamide (Cytoxan, CTX) on premature ovarian failure (POF) in mice and its regulatory mechanisms by transcriptome analysis. MAIN METHODS: Female C57BL/6 mice were treated with a single intraperitoneal injection of 70 mg/kg CTX. Serum levels of estradiol (E2) and follicle stimulating hormone (FSH) were measured by enzyme-linked immunosorbent assay (ELISA), and follicular structure differences were observed by hematoxylin and eosin (H&E) staining. The main mechanism of POF was investigated by RNA-seq data, protein-protein interaction (PPI) networks and qPCR analysis. KEY FINDINGS: The serum levels of E2 were significantly decreased and those of FSH were significantly increased compared to the control group. The ovarian weights of the mice in the CTX group were reduced, and abnormal follicular structures were also observed in the CTX group. The RNA-seq data show that the downregulated genes were related to the cholesterol biosynthesis pathway. The PPI network and qPCR analyses further confirm that the PPAR signaling pathway and the ovarian infertility genes were also involved in blocking the cholesterol biosynthesis pathway. The differences were statistically significant. SIGNIFICANCE: Our results indicate that CTX may exert its anti-tumor effects by inactivating the cholesterol biosynthesis pathway, and simultaneously reducing the supply of estrogen precursor materials, ultimately leading to the occurrence of POF. Our data provided a preliminary theoretical basis for resolving the clinical toxicity and side effects of CTX.


Assuntos
Antineoplásicos Alquilantes/toxicidade , Colesterol/biossíntese , Ciclofosfamida/toxicidade , Perfilação da Expressão Gênica , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/metabolismo , Animais , Regulação para Baixo/efeitos dos fármacos , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/biossíntese , Redes e Vias Metabólicas/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/patologia , Receptores Ativados por Proliferador de Peroxissomo/genética , Insuficiência Ovariana Primária/genética , Mapas de Interação de Proteínas
7.
J Ovarian Res ; 12(1): 91, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31585548

RESUMO

BACKGROUND: A retrospective case-control study was performed to evaluate whether PCOS-specific serum markers would change in women with polycystic ovary syndrome (PCOS) during the course of two consecutive cycles of clomiphene citrate (CC)-stimulation, which did not lead to a pregnancy. METHODS: Anovulatory PCOS patients who underwent two consecutive CC-cycles (n = 41) and anovulatory PCOS controls who chose an observational approach for two months (n = 24) were included in the study. The main outcome measures were levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), anti-Mullerian hormone (AMH), total testosterone, androstenedione, and sexual hormone binding globulin (SHBG). RESULTS: In the control group, PCOS-specific serum parameters did not change during two months (p > 0.05). In the CC-group, there were decreases in LH (11.8 ± 4.9 mU/mL vs. 10.9 ± 4.0 mU/mL; p = 0.029), the LH:FSH ratio (2.1 ± 0.8 mU/mL vs. 1.8 ± 0.5 mU/mL; p = 0.007), and AMH (8.08 ± 4.27 ng/mL vs. 7.17 ± 3.37 ng/mL; p = 0.011), as well as an increase in SHBG (46.0 ± 20.2 nmol/L vs. 51.2 ± 21.0 nmol/L; p < 0.001). A higher age and lower baseline total testosterone and AMH levels were predictive of an AMH decline (p < 0.05). CONCLUSION: Two cycles of CC-stimulation that did not lead to a pregnancy were accompanied by mean LH, AMH, and LH:FSH ratio declines and an SHBG increase. The clinical significance seems of minor relevance.


Assuntos
Biomarcadores/sangue , Clomifeno/administração & dosagem , Folículo Ovariano/efeitos dos fármacos , Síndrome do Ovário Policístico/sangue , Adulto , Androstenodiona/sangue , Hormônio Antimülleriano/sangue , Estudos de Casos e Controles , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Folículo Ovariano/patologia , Indução da Ovulação , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/patologia , Gravidez , Estudos Retrospectivos , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/sangue
8.
Hum Genet ; 138(11-12): 1227-1236, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31535215

RESUMO

Premature ovarian insufficiency (POI) is a major cause of reduced female fertility and affects approximately 1% women under 40 years of age. Recent advances emphasize the genetic heterogeneity of POI. Fanconi anemia (FA) genes, traditionally known for their essential roles in DNA repair and cytogenetic instability, have been demonstrated to be involved in meiosis and germ cell development. Here, we conducted whole-exome sequencing (WES) in 50 Han Chinese female patients with POI. Rare missense variants were identified in FANCA (Fanconi anemia complementation group A): c.1772G > A (p.R591Q) and c.3887A > G (p.E1296G). Both variants are heterozygous in the patients and very rare in the human population. In vitro functional studies further demonstrated that these two missense variants of FANCA exhibited reduced protein expression levels compared with the wild type, suggesting the partial loss of function. Moreover, mono-ubiquitination levels of FANCD2 upon mitomycin C stimulation were significantly reduced in cells overexpressing FANCA variants. Furthermore, a loss-of-function mutation of Fanca was generated in C57BL/6 mice for in vivo functional assay. Consistently, heterozygous mutated female mice (Fanca+/-) showed reduced fertility and declined numbers of follicles with aging when compared with the wild-type female mice. Collectively, our results suggest that heterozygous pathogenic variants in FANCA are implicated in non-syndromic POI in Han Chinese women, provide new insights into the molecular mechanisms of POI and highlight the contribution of FANCA variants in female subfertility.


Assuntos
Proteína do Grupo de Complementação A da Anemia de Fanconi/genética , Infertilidade Feminina/etiologia , Mutação , Folículo Ovariano/patologia , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/patologia , Adulto , Animais , Feminino , Heterozigoto , Humanos , Infertilidade Feminina/patologia , Camundongos , Camundongos Endogâmicos C57BL , Folículo Ovariano/metabolismo , Ubiquitinação
9.
Int J Mol Sci ; 20(19)2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31548505

RESUMO

Ovarian follicle pool depletion, infertility, and premature menopause are all known sequelae of cancer treatment that negatively impact the quality of life of young cancer survivors. The mechanisms involved in this undesired iatrogenic ovarian damage have been intensively studied, but many of them remain unclear. Several chemotherapeutic drugs have been shown to induce direct and indirect DNA-damage and/or cellular stress, which are often followed by apoptosis and/or autophagy. Damage to the ovarian micro-vessel network induced by chemotherapeutic agents also seems to contribute to ovarian dysfunction. Another proposed mechanism behind ovarian follicle pool depletion is the overactivation of primordial follicles from the quiescent pool; however, current experimental data are inconsistent regarding these effects. There is great interest in characterizing the mechanisms involved in ovarian damage because this might lead to the identification of potentially protective substances as possible future therapeutics. Research in this field is still at an experimental stage, and further investigations are needed to develop effective and individualized treatments for clinical application. This review provides an overview of the current knowledge and the proposed hypothesis behind chemotherapy-induced ovarian damage, as well as current knowledge on possible co-treatments that might protect the ovary and the follicles from such damages.


Assuntos
Sobreviventes de Câncer , Fertilidade , Infertilidade Feminina , Doenças Ovarianas , Folículo Ovariano , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Feminino , Humanos , Infertilidade Feminina/induzido quimicamente , Infertilidade Feminina/metabolismo , Infertilidade Feminina/patologia , Infertilidade Feminina/terapia , Doenças Ovarianas/induzido quimicamente , Doenças Ovarianas/metabolismo , Doenças Ovarianas/patologia , Doenças Ovarianas/terapia , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Qualidade de Vida
10.
Mol Biol Rep ; 46(5): 4675-4684, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31529342

RESUMO

The purpose of this study was to test the hypothesis that different cytokine profiles may exist in the follicular fluid of endometriosis (EM) patients undergoing in vitro fertilization (IVF), as these differences may provide insights into the pathogenesis of the disease. This was a cross-sectional study conducted at the reproductive center of a medical university hospital. The study included 49 patients receiving IVF. 20 infertile women with proven EM and 29 women without diagnosed EM (control group) were evaluated. Follicular fluid (FF) and serum were collected at the time of follicle aspiration and the concentrations of 38 cytokines were determined by multiplexed immunoassay. The results indicated that the levels of IL-4, IL-13, IL-3 and IL-1α were significantly increased in the FF of women with EM, while levels of IFN-γ, IL-17A, MDC and MIP-1α were decreased compared with in the control subjects. In conclusions, the immune microenvironment of the FF in patients with EM is altered. This may contribute to the pathologic mechanism responsible for the poor outcome of IVF in patients with EM.


Assuntos
Microambiente Celular/imunologia , Endometriose/diagnóstico , Endometriose/etiologia , Folículo Ovariano/imunologia , Biomarcadores , Citocinas/biossíntese , Citocinas/sangue , Endometriose/metabolismo , Feminino , Fertilização In Vitro/efeitos adversos , Líquido Folicular/imunologia , Líquido Folicular/metabolismo , Hormônios/sangue , Hormônios/metabolismo , Humanos , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia
11.
Gene ; 721: 144106, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31499126

RESUMO

The modified prolonged gonadotropin-releasing hormone agonist (GnRH-a) protocol lessens the ovarian hyperstimulation syndrome (OHSS) effect and improves the clinical pregnancy rate of women with polycystic ovary syndrome (PCOS) compared with the standard long GnRH-a protocol. However, the molecular basis of this process needs to be elucidated. Sprague Dawley (SD) female rats with letrozole-induced PCOS were divided into GnRH-a and blank groups. Rats in the GnRH-a group were given triptorelin for 11 days, whereas those in blank group were given an equal volume of 0.9% NaCl. Meanwhile, the changes in estrus cycle, hormonal profile, ovary index, ovarian histopathology and body weight were measured. The expressions of anti-mullerian hormone (AMH), type II receptor of AMH (AMHRII), and FSH receptor (FSHR) were taken as the indicators of follicular sensitivity. Changes of follicular counting and differences in antral follicle diameter at each stage were evaluated. The number of follicles from primordial to antral stages increased during downregulation and the differences in antral follicle diameter were reduced in the GnRH-a group, whereas no significant difference was found in the blank group. The results of Western blotting and ELISA indicated that the level of AMH in ovarian total protein and serum had a similar dynamic change in the GnRH-a group. The results of immunohistochemistry showed that follicular AMH, AMHRII, and FSHR significantly decreased in the GnRH-a group. Prolonged GnRH-a protocol can improve synchronization and sensitivity of follicular development by balancing the expressions of AMH, AMHRII, and FSHR among follicles at all levels, thereby achieving better therapeutic effect.


Assuntos
Hormônio Antimülleriano/metabolismo , Regulação para Baixo/efeitos dos fármacos , Letrozol/efeitos adversos , Folículo Ovariano/metabolismo , Síndrome do Ovário Policístico , Animais , Feminino , Hormônio Foliculoestimulante/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Letrozol/farmacologia , Folículo Ovariano/patologia , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Ratos , Ratos Sprague-Dawley , Receptores do FSH/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo
12.
Anim Reprod Sci ; 209: 106142, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31514932

RESUMO

Haemorrhagic anovulatory follicles (HAFs) are the most common pathological anovulatory condition in the mare. To enhance understanding of the physiopathology of HAFs, the aim of the present study was to determine the effects of an induced-follicular wave on LH concentrations and follicular fluid factors relevant to the ovulatory process. Mares were allocated to treatment or control groups (n = 7/group) in a crossed over design during 14 oestrous cycles with a period of one cycle occurring when there were no treatments between the times when treatments were administered. In the treatment group, all antral follicles ≥8 mm were ablated on Day 10 after ovulation followed by administration of a luteolytic dose of PGF2α. All mares of both groups were treated with 1500 IU of hCG when a follicle ≥32 mm was detected (Hour 0), and follicular fluid was aspirated 35 h later. Blood samples were collected every 48 h from Day 10 until Hour 0 from all mares. Follicular fluid was assayed for PGE2, estradiol and progesterone. Plasma was assayed for LH concentrations. A follicular wave followed follicle ablation in the treated mares. Concentrations of LH were greater (P = 0.05) in mares ot the treatment compared with control group. Concentrations of PGE2, estradiol and progesterone in follicular fluid did not differ between groups (P > 0.05). Treatment resulted in an earlier increase in circulating LH, however, there was no effect on concentrations of intra-follicular PGE2, estradiol or progesterone in hCG-stimulated preovulatory follicles.


Assuntos
Técnicas de Ablação , Anovulação/cirurgia , Líquido Folicular/metabolismo , Cavalos , Hormônio Luteinizante/sangue , Luteólise/efeitos dos fármacos , Folículo Ovariano/cirurgia , Técnicas de Ablação/métodos , Técnicas de Ablação/veterinária , Animais , Anovulação/complicações , Anovulação/metabolismo , Anovulação/veterinária , Gonadotropina Coriônica/farmacologia , Estudos Cross-Over , Dinoprosta/farmacologia , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/metabolismo , Feminino , Líquido Folicular/química , Líquido Folicular/efeitos dos fármacos , Hemorragia/complicações , Hemorragia/cirurgia , Hemorragia/veterinária , Doenças dos Cavalos/metabolismo , Doenças dos Cavalos/cirurgia , Folículo Ovariano/diagnóstico por imagem , Folículo Ovariano/patologia , Ovulação/efeitos dos fármacos , Indução da Ovulação/métodos , Indução da Ovulação/veterinária , Punções/métodos , Punções/veterinária , Ultrassonografia de Intervenção/métodos , Ultrassonografia de Intervenção/veterinária
13.
Anim Reprod Sci ; 209: 106164, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31514938

RESUMO

A common reproductive disease in dairy cattle is Cystic Ovarian Disease. To study its development, there was use of an experimental model of follicular persistence to detect hemodynamic changes occurring in ovaries by using Doppler ultrasonography. After estrous synchronization, control cows received no additional treatment and were evaluated at proestrus (CG), whereas treated cows (PG) received sub-luteal doses of progesterone for 15 days and were evaluated at proestrus, and after 0, 5, 10 and 15 days of follicular persistence. Spectral Doppler was used to evaluate blood flow in the ovarian artery, and power Doppler for evaluation of blood flow in the ovarian parenchyma and follicular wall of persistent and dominant preovulatory follicles. Findings using power Doppler signals indicated there were no differences between groups in the parenchyma of both right (P =  0.455) and left (P =  0.762) ovaries. In contrast, power Doppler signals of blood flow were less in walls of persistent follicles from day 0 to 15 when there was follicular persistence than in dominant follicles of the CG (P <  0.001). Blood flow in ovarian arteries was less (P <  0.05) in diastolic velocity and time averaged maximum velocity in all PG groups than in the CG. Peak systolic velocity was less (P <  0.05) in all PG than in the CG, with the exception of P15 (P >  0.05). These findings indicate there are marked changes in blood irrigation area of walls of persistent follicles during the 15 days of follicular persistence.


Assuntos
Doenças dos Bovinos/diagnóstico , Hemodinâmica/fisiologia , Cistos Ovarianos/diagnóstico , Ovário/irrigação sanguínea , Ovário/diagnóstico por imagem , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Bovinos , Doenças dos Bovinos/patologia , Doenças dos Bovinos/fisiopatologia , Indústria de Laticínios , Progressão da Doença , Sincronização do Estro/métodos , Feminino , Hemodinâmica/efeitos dos fármacos , Dispositivos Intrauterinos Medicados/veterinária , Cistos Ovarianos/patologia , Cistos Ovarianos/fisiopatologia , Folículo Ovariano/diagnóstico por imagem , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/patologia , Ovário/efeitos dos fármacos , Ovário/patologia , Progesterona/farmacologia , Ultrassonografia Doppler/veterinária
14.
Endocr Regul ; 53(3): 146-153, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31517633

RESUMO

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common and multifactorial disease associated with female factor infertility. Ulmus minor bark (UMB) is one of the medicinal plants used in Persian folklore as a fertility enhancer. In the current study, we aimed to elucidate the effect of UMB hydro-alcoholic extract on histological parameters and testosterone condition in an experimental model of PCOS rats. METHODS: Thirty female rats were randomly divided into five groups: (1) control, (2) vehicle, (3) PCOS/50 mg [6 mg/kg dehydroepiandrosterone (DHEA) + 50 mg/kg UMB hydro-alcoholic extract], (4) PCOS/150 mg (6 mg/kg DHEA + 150 mg/kg UMB hydro-alcoholic extract), and (5) PCOS (6 mg/kg DHEA). All interventions were performed for 21 days. Afterwards, stereological analysis was done for determination of ovarian volume and follicle number. The serum level of testosterone was measured by ELISA kit. RESULTS: UMB hydro-alcoholic extract improved the total number of the corpus luteum in the treatment groups when compared to the PCOS group (p<0.05). PCOS/150 mg and PCOS/50 mg groups showed significantly lower total number of the primordial, primary, and secondary follicles as well as testosterone level compared to the PCOS group (p<0.05). The total number of antral follicles and volume of ovary did not differ significantly between groups. CONCLUSION: UMB extract may be an effective and good alternative in improving PCOS histo-logical and testosterone disturbances although further studies are warranted to confirm the safety of UMB plant in human.


Assuntos
Ovário/efeitos dos fármacos , Casca de Planta/química , Extratos Vegetais/farmacologia , Síndrome do Ovário Policístico/patologia , Testosterona/sangue , Ulmus/química , Animais , Modelos Animais de Doenças , Etanol/química , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Infertilidade Feminina/sangue , Infertilidade Feminina/patologia , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/patologia , Ovário/patologia , Fitoterapia , Síndrome do Ovário Policístico/sangue , Ratos , Água/química
15.
Zygote ; 27(5): 285-298, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31412964

RESUMO

Ovulation is considered an inflammatory, cytokine-mediated event. Cytokines, which are recognized as growth factors with immunoregulatory properties, are involved in many cellular processes at the ovarian level. In this sense, cytokines affect fertility and are involved in the development of different ovarian disorders such as bovine cystic ovarian disease (COD). Because it has been previously demonstrated that ovarian cells represent both sources and targets of cytokines, the aim of this study was to examine the expression of several cytokines, including IL-1ß, IL-1RA, IL-1RI, IL-1RII, IL-4 and IL-8, in ovarian follicular structures from cows with spontaneous COD. The protein expression of these cytokines was evaluated by immunohistochemistry. Additionally, IL-1ß, IL-4 and IL-8 concentrations in follicular fluid (FF) and serum were determined by enzyme-linked immunosorbent assay (ELISA). In granulosa and theca cells, IL-1RI, IL-1RII, IL-1RA and IL-4 expression levels were higher in cystic follicles than in the control dominant follicles. The serum and FF concentrations of IL-1ß and IL-4 showed no differences between groups, whereas IL-8 concentration was detected only in FF of cysts from cows with COD. The FF and serum concentrations of IL-1ß and IL-8 showed no significant differences, whereas IL-4 concentration was higher in FF than in serum in both the control and COD groups. These results evidenced an altered expression of cytokines in ovaries of cows with COD that could contribute to the pathogenesis of this disease.


Assuntos
Líquido Folicular/metabolismo , Interleucinas/metabolismo , Cistos Ovarianos/metabolismo , Cistos Ovarianos/patologia , Animais , Estudos de Casos e Controles , Bovinos , Doenças dos Bovinos , Feminino , Proteína Antagonista do Receptor de Interleucina 1/sangue , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Interleucina-1beta/metabolismo , Interleucina-4/sangue , Interleucina-4/metabolismo , Interleucina-8/sangue , Interleucina-8/metabolismo , Cistos Ovarianos/veterinária , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Receptores Tipo I de Interleucina-1/metabolismo , Receptores Tipo II de Interleucina-1/metabolismo
16.
J Assist Reprod Genet ; 36(10): 2181-2189, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31422495

RESUMO

PURPOSE: Almost every female classic galactosemia patient develops primary ovarian insufficiency (POI). The unique pathophysiology of classic galactosemia, with a severely reduced follicle pool at an early age, requires a new therapeutic approach. This study evaluated the effect of dehydroepiandrosterone (DHEA) on ovarian tissue in a galactose-induced POI rat model. METHODS: Pregnant rats were fed with either a normal or a 35% galactose-containing diet from day 3 of conception continuing through weaning of the litters. Galactose-exposed female offspring were further divided into 5 groups on PND21. The first group received no application. Treatment groups were fed orally by gavage once daily with sesame oil (group 2), or DHEA at doses of 0.1 mg/kg (group 3), 1 mg/kg (group 4) or 10 mg/kg (group 5) until PND70. Fertility rates of mothers with galactosemia, body weights (BWs), and ovarian weights of the litters from PND21 to PND70 were recorded. Ovarian follicle count, immunohistochemistry for proliferation and apoptosis marker expressions and TUNEL for cell death assessment were performed in offspring ovaries. RESULTS: Decreased fertility, ovarian/body weights were observed under galactosemic conditions, together with decreased follicle number and increased atresia. Improved postnatal development, primordial follicle recruitment and follicular growth were observed after DHEA treatment. After DHEA treatment, the expression of Ki67 protein was found to be increased; elevated expression of cleaved-caspase-3 under galactosemia was found to be reduced. CONCLUSIONS: Our data suggests that DHEA treatment may be a potentially useful clinical therapy to improve ovarian ageing in women with POI-induced by galactosemia.


Assuntos
Envelhecimento/efeitos dos fármacos , Desidroepiandrosterona/farmacologia , Galactosemias/dietoterapia , Insuficiência Ovariana Primária/dietoterapia , Envelhecimento/genética , Animais , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Galactose/toxicidade , Galactosemias/induzido quimicamente , Galactosemias/complicações , Galactosemias/patologia , Humanos , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/patologia , Gravidez , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/patologia , Ratos
17.
Toxicol Appl Pharmacol ; 381: 114714, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31437492

RESUMO

Ovarian toxicity and infertility are major side effects of cancer therapy in young female cancer patients. We and others have previously demonstrated that doxorubicin (DOX), one of the most widely used chemotherapeutic chemicals, has a dose-dependent toxicity on growing follicles. However, it is not fully understood if the primordial follicles are the direct or indirect target of DOX. Using both prepubertal and young adult female mouse models, we comprehensively investigated the effect of DOX on all developmental stages of follicles, determined the impact of DOX on primordial follicle survival, activation, and development, as well as compared the impact of age on DOX-induced ovarian toxicity. Twenty-one-day-old CD-1 female mice were intraperitoneally injected with PBS or clinically relevant dose of DOX at 10 mg/kg once. Results indicated that DOX primarily damaged granulosa cells in growing follicles and oocytes in primordial follicles and DOX-induced growing follicle apoptosis was associated with the primordial follicle overactivation. Using the 5-day-old female mice with a more uniform primordial follicle population, our data revealed that DOX also directly promoted primordial follicle death and the DNA damage-TAp63α-C-CASP3 pathway was involved in DOX-induced primordial follicle oocyte apoptosis. Compared to 21-day- and 8-week-old female mice that were treated with the same dose of DOX, the 5-day-old mice had the most severe primordial follicle loss as well as the least degree of primordial follicle overactivation. Taken together, these results demonstrate that DOX obliterates mouse ovarian reserve through both primordial follicle atresia and overactivation and the DOX-induced ovarian toxicity is age dependent.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Doxorrubicina/efeitos adversos , Atresia Folicular/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Reserva Ovariana/efeitos dos fármacos , Animais , Dano ao DNA , Feminino , Camundongos , Folículo Ovariano/patologia
18.
Niger J Physiol Sci ; 34(1): 49-53, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31449271

RESUMO

Trypanosomosis has been described as the single largest disease entity limiting livestock development in sub-Saharan Africa. The effects on ovarian weight, follicle count and retrieved oocyte characteristics in ten West African dwarf goat does (control=5, infected=5) experimentally infected with Trypanosoma brucei were investigated. The does were fed with elephant grass and supplement (15.23% CP) daily. Infected does received 4.8x105 T. brucei intravenously and thereafter, all does were synchronized using Lutalyse®. The results showed that the differences between control and infected does for ovarian weight (0.68±0.56 g and 0.40±0.09 g) and follicle count (10.50±1.25 and 2.50±1.22),  respectively were significant (P<0.05). The difference in retrieved-oocytes-count between control (30, 57.7%) and infected (22, 42.3%)  does was not significant (P>0.05). The differences in proportion between control and infected does for well-formed-oocytes (90.5% and 9.5%), completely-denuded-oocytes (30.8% and 69.2%) and proportion per group of oocytes with substantial-investment-of-cumulus (63.3% and 9.1%), respectively were significant (P<0.05). The difference in extensively-denuded-oocytes between control (38.9%) and infected (61.1%) does was not significant (P>0.05). These findings suggest that experimental Trypanosoma brucei infection caused reduction in ovarian weight and follicle count, number of oocytes as well as proportion of well-formed oocytes that are capable of supporting embryonic development.


Assuntos
Recuperação de Oócitos/métodos , Oócitos/patologia , Folículo Ovariano/patologia , Trypanosoma brucei brucei , Tripanossomíase Africana/patologia , Animais , Feminino , Cabras , Nigéria , Tamanho do Órgão , Ovário/patologia , Gravidez
20.
Geroscience ; 41(4): 395-408, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31359237

RESUMO

Caloric restriction (CR) increases the preservation of the ovarian primordial follicular reserve, which can potentially delay menopause. Rapamycin also increases preservation on the ovarian reserve, with similar mechanism to CR. Therefore, the aim of our study was to evaluate the effects of rapamycin and CR on metabolism, ovarian reserve, and gene expression in mice. Thirty-six female mice were allocated into three groups: control, rapamycin-treated (4 mg/kg body weight every other day), and 30% CR. Caloric restricted females had lower body weight (P < 0.05) and increased insulin sensitivity (P = 0.003), while rapamycin injection did not change body weight (P > 0.05) and induced insulin resistance (P < 0.05). Both CR and rapamycin females displayed a higher number of primordial follicles (P = 0.02 and 0.04, respectively), fewer primary, secondary, and tertiary follicles (P < 0.05) and displayed increased ovarian Foxo3a gene expression (P < 0.05). Despite the divergent metabolic effects of the CR and rapamycin treatments, females from both groups displayed a similar increase in ovarian reserve, which was associated with higher expression of ovarian Foxo3a.


Assuntos
Restrição Calórica , Imunossupressores/farmacologia , Folículo Ovariano/patologia , Reserva Ovariana , Sirolimo/farmacologia , Animais , Peso Corporal , Feminino , Proteína Forkhead Box O3/genética , Proteína Forkhead Box O3/metabolismo , Expressão Gênica , Resistência à Insulina , Camundongos Endogâmicos C57BL , Ovário/metabolismo , RNA/metabolismo
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