Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 10.563
Filtrar
1.
Int J Mol Sci ; 22(9)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068748

RESUMO

Estrogen receptor beta (ERß) plays a critical role in granulosa cell (GC) functions. The existence of four human ERß splice isoforms in the ovary suggests their differential implication in 17ß-estradiol (E2) actions on GC apoptosis causing follicular atresia. In this study, we investigated whether E2 can regulate ERß isoforms expression to fine tune its apoptotic activities in human GC. For this purpose, we measured by RT-qPCR the expression of ERß isoforms in primary culture of human granulosa cells (hGCs) collected from patients undergoing in vitro fertilization, before and after E2 exposure. Besides, we assessed the potential role of ERß isoforms on cell growth and apoptosis after their overexpression in a human GC line (HGrC1 cells). We confirmed that ERß1, ERß2, ERß4, and ERß5 isoform mRNAs were predominant over that of ERα in hGCs, and found that E2 selectively regulates mRNA levels of ERß4 and ERß5 isoforms in these cells. In addition, we demonstrated that overexpression of ERß1 and ERß4 in HGrC1 cells increased cell apoptosis by 225% while ERß5 or ERß2 had no effect. Altogether, our study revealed that E2 may influence GC fate by specifically regulating the relative abundance of ERß isoforms mRNA to modulate the balance between pro-apoptotic and non-apoptotic ERß isoforms.


Assuntos
Estradiol/farmacologia , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Células da Granulosa/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Ovário/efeitos dos fármacos , Isoformas de Proteínas/genética , RNA Mensageiro/genética
2.
Aquat Toxicol ; 236: 105873, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34082366

RESUMO

To study the effects of exposure of fish to opioid drugs, we exposed Japanese medaka (Oryzias latipes) over a full life cycle to codeine spiked into river water at nominal concentrations of 100, 1,000 and 25,000 ng/L and to fentanyl spiked into river water at nominal concentrations of 5, 25 and 1,000 ng/L. The measured concentrations during medaka exposures were consistent with the nominal concentrations. Treatments with codeine at all test concentrations reduced the number of eggs produced by female medaka, as well as the number of mature oocytes observed histologically in the ovaries. Exposures to codeine also resulted in altered concentrations of hormones within the hypothalamic-pituitary-gonadal axis, including reduced levels of 17ß-estradiol in female medaka. Fentanyl did not affect reproduction or the levels of hormones in medaka at the concentrations tested. Monitoring of surface waters in southern Ontario, Canada downstream of wastewater treatment plants showed that the test concentrations of fentanyl and codeine were environmentally relevant. The results of this work contribute to the literature on the impacts of opioids and other drugs of abuse released into surface waters.


Assuntos
Analgésicos Opioides/toxicidade , Oryzias/fisiologia , Poluentes Químicos da Água/toxicidade , Animais , Estradiol/farmacologia , Feminino , Estágios do Ciclo de Vida/efeitos dos fármacos , Masculino , Ontário , Ovário/efeitos dos fármacos , Reprodução/efeitos dos fármacos
3.
BMC Pregnancy Childbirth ; 21(1): 348, 2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-33934703

RESUMO

BACKGROUND: No previous study directly compares the fixed day-5 initiation versus the flexible initiation of GnRH antagonist administration in IVF/ICSI for those patients who are predicted as high ovarian responders without PCOS. To evaluate whether the number of oocytes retrieved is different by using the two GnRH antagonist protocols in Chinese women with predicted high ovarian response except PCOS. METHODS: A randomized controlled trial of 201 infertile women with predicted high ovarian response except PCOS undergoing in vitro fertilization. Ovary stimulation was performed using recombinant FSH and GnRH antagonists. GnRH antagonist ganirelix (0.25 mg/d) was started either on day 5 of stimulation (fixed group) or when LH was > 10 IU/L, and/or a follicle with mean diameter > 12 mm was present, and/or serum E2 was > 600 pg/ml. Patient monitoring was initiated on day 3 of stimulation in flexible group. RESULT(S): No significant difference was observed between the fixed and flexible groups regarding the number of oocytes retrieved (16.72 ± 7.25 vs. 17.47 ± 5.88, P = 0.421), the Gonadotropin treatment duration (9.53 ± 1.07 vs. 9.67 ± 1.03, P = 0.346) and total Gonadotropin dose (1427.75 ± 210.6 vs. 1455.94 ± 243.44, P = 0.381). GnRH antagonist treatment duration in fixed protocol was statistically longer than the flexible protocol (6.57 ± 1.17 vs 6.04 ± 1.03, P = 0.001). There was no premature LH surge in either protocol. CONCLUSION(S): Fixed GnRH antagonist administration on day 5 of stimulation appear to achieve a comparable oocyte retrieved compared with flexible antagonist administration. TRIAL REGISTRATION: NCT02635607 posted on December 16, 2015 in clinicaltrials.gov.


Assuntos
Infertilidade Feminina/terapia , Ovário/efeitos dos fármacos , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/fisiopatologia , Adulto , Gonadotropina Coriônica/administração & dosagem , Feminino , Fertilização In Vitro/métodos , Hormônio Foliculoestimulante Humano/administração & dosagem , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/análogos & derivados , Humanos , Infertilidade Feminina/fisiopatologia , Ovário/metabolismo , Ovário/fisiopatologia , Síndrome do Ovário Policístico/complicações , Gravidez , Taxa de Gravidez , Proteínas Recombinantes/administração & dosagem , Resultado do Tratamento , Pamoato de Triptorrelina/administração & dosagem , Adulto Jovem
4.
J Vis Exp ; (170)2021 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-33900289

RESUMO

Live imaging of Drosophila melanogaster ovaries has been instrumental in understanding a variety of basic cellular processes during development, including ribonucleoprotein particle movement, mRNA localization, organelle movement, and cytoskeletal dynamics. There are several methods for live imaging that have been developed. Due to the fact that each method involves dissecting individual ovarioles placed in media or halocarbon oil, cellular damage due to hypoxia and/or physical manipulation will inevitably occur over time. One downstream effect of hypoxia is to increase oxidative damage in the cells. The purpose of this protocol is to use live imaging to visualize the effects of oxidative damage on the localization and dynamics of subcellular structures in Drosophila ovaries after induction of controlled cellular damage. Here, we use hydrogen peroxide to induce cellular oxidative damage and give examples of the effects of such damage on two subcellular structures, mitochondria and Clu bliss particles. However, this method is applicable to any subcellular structure. The limitations are that hydrogen peroxide can only be added to aqueous media and would not work for imaging that uses halocarbon oil. The advantages are that hydrogen peroxide is readily available and inexpensive, acts quickly, its concentrations can be modulated, and oxidative damage is a good approximation of damage caused by hypoxia as well as general tissue damage due to manipulation.


Assuntos
Drosophila melanogaster , Ovário/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Feminino , Peróxido de Hidrogênio/farmacologia , Microscopia , Mitocôndrias/efeitos dos fármacos , Ovário/citologia , Oxidantes/farmacologia
5.
Molecules ; 26(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803091

RESUMO

Although melatonin has been extensively studied in animal reproduction, the mechanism of melatonin in puberty remains elusive. This study was designed to explore the effect of intraperitoneal administration of melatonin on puberty onset in female mice. The injection of melatonin into postnatal days 10 mice at a dose of 15 mg/kg accelerated the puberty onset in mice. Mechanistically, there was no difference in physical growth and serum Leptin levels after melatonin administration. Meanwhile, the serum levels of reproductive hormones involved in hypothalamic-pituitary-ovarian axis, such as FSH and estrogen level in serum were increased. The mRNA levels of GnRH and GnRHr were not affected by melatonin, while the expressions of FSHß in pituitary and Cyp19a1 in ovary were significantly up-regulated. In addition, melatonin still promoted FSH synthesis after ovariectomy. Furthermore, the enhanced activity of ERK1/2 signaling verified that the expression of FSHß increased in pituitary. We confirmed that melatonin promoted the FSH synthesis in pituitary, thereby increased serum estrogen levels and ultimately accelerated puberty onset. However, these effects of melatonin may be pharmacological due to the high dose. This study would help us to understand the functions of melatonin in pubertal regulation comprehensively.


Assuntos
Hormônio Foliculoestimulante/metabolismo , Melatonina/farmacologia , Maturidade Sexual/efeitos dos fármacos , Animais , Aromatase/metabolismo , China , Estrogênios/metabolismo , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Injeções Intraperitoneais , Leptina/metabolismo , Hormônio Luteinizante/metabolismo , Melatonina/metabolismo , Camundongos , Ovário/efeitos dos fármacos , Hipófise/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Receptores LHRH/metabolismo , Maturidade Sexual/fisiologia
6.
Res Vet Sci ; 136: 519-526, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33882380

RESUMO

It is known that immunizing gilts against gonadotropin-releasing hormone (GnRH) is an efficient castration method that increases their growth performance. However, it is still unknown the ovarian histophysiology outcomes after this procedure. Therefore, the aim of this study was to investigate in detail, using morphological and morphometrical methods, changes in the ovarian structure that result in the suppression of ovarian activity, as well as to gain knowledge on the ovarian structure to assist in ovarian histopathological diagnoses. Seventy-two pre-pubertal finishing gilts were allocated to two experimental groups: immunized (IC; n = 36; gilts which received two injections of 2 mL of Vivax® - one at 15 and another at 19 weeks of age) and control (CT; n = 36, females which received two saline injections following the same protocol). All gilts were euthanized at 25 weeks of age and the ovaries of 5 gilts from each experimental group collected for biometrical and histomorphometrical analysis. IC gilts showed higher body weights, but smaller ovaries compared to CT females. In addition, the number of small follicles (≤ 2 mm) on the ovarian surface was higher, while no large follicles (> 6 mm) nor corpora lutea were found in the ovaries of IC gilts. Histomorphometrical analysis revealed that IC females showed higher numbers of quiescent and active primordial, primary, pre-antral and final stage atretic follicles. Moreover, follicle size, antrum diameter and area of the granulosa layer from mature follicles were smaller in IC gilts. Collectively, these results demonstrate that the efficacy of immunization against GnRH is related to the blockage of follicular recruitment and selection, thus suppressing reproductive activity in finishing gilts.


Assuntos
Hormônio Liberador de Gonadotropina/imunologia , Imunização/veterinária , Ovariectomia , Ovário/anatomia & histologia , Reprodução/imunologia , Suínos , Animais , Corpo Lúteo , Feminino , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Ovário/efeitos dos fármacos
7.
Res Vet Sci ; 135: 557-567, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33541712

RESUMO

The aim of this study was to evaluate if the cottonseed intake during gestation and lactation affects the ovarian population in ewes and lambs. Therefore, 39 ewes were evaluated during 10 months under two treatments: Cottonseed and soybeans. The quantification of ovarian follicular dynamics was analyzed by ultrasound and the determination of progesterone and estradiol levels was interpreted by radioimmunoassay. After weaning, ovaries of lambs (n = 10) were collected by ovariectomy and fixed for the assessment of follicular parameters as normality, classification, diameter, ultrastructure, stereology, and as well as immunoexpression of the α-estradiol receptor α (ER-α). The results showed that the cottonseed consumption altered neither the ovarian nor the hormonal follicular dynamics of Santa Inês ewes after calving and did not affect the normality, classification, diameter, stereology and follicular ultrastructure of offspring. Nevertheless, the offspring of ewes fed with cottonseed showed high ER-α immunoexpression in the ovarian structures. It is concluded that cottonseed did not affect the maternal-descendant follicular dynamics. However, lambs' ovaries had highest α-ER immunoexpression in oocytes, granulosa and theca cells and corpus luteum. This fact warns of a possible change in the future steroidogenic response of these lambs that had progenitors consuming cottonseed in their reproductive period.


Assuntos
Gossipol/farmacologia , Ovário/efeitos dos fármacos , Ovinos , Animais , Feminino , Gossipol/administração & dosagem , Lactação , Oócitos/metabolismo , Gravidez , Progesterona , Reprodução
8.
Biomed Pharmacother ; 135: 111204, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33548869

RESUMO

BACKGROUND: Progestational stress has been proven to be a risk for the neural development of offspring, especially in the hippocampus. However, whether Chaihu Shugan San (CSS) can ameliorate hippocampal neural development via the regulation of brain-derived neurotrophic factor (BDNF), and N-methyl-D-aspartate receptors (NMDAR) 2A (NR2A) and 2B (NR2B), and the mechanism of such action remains unclear. METHODS: Thirty-six female rats were randomly allocated into control, chronic immobilization stress (CIS) and CSS groups according to the random number table, respectively. The male offspring were fed for 21 days after birth then randomly divided into the same three groups (6 rats/group) as the female rats. Female rats, except for the control group, underwent 21-day CIS to established a progestational stress anxiety-like model which was evaluated by body weight, the elevated plus-maze (EPM) test and serum dopamine (DA) measured using an enzyme-linked immunosorbent assay (ELISA). The expression levels of estrogen receptors (ERα/ERß) and progesterone receptor (PR) in female rat ovaries were quantified by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. The hippocampal tissue in the 21-day offspring was observed by hematoxylin-eosin (HE) staining. The concentration of BDNF, NR2A, and NR2B were measured by RT-qPCR and immunohistochemistry in the CA3 and dentate gyrus (DG) regions of offsprings' hippocampus. RESULTS: Compared with the female control group, significant differences in body weight, EPM test and DA concentration were observed in the CIS group, meanwhile, the concentration of ERα (P < 0.05), PR (P < 0.05) and ERß in the ovaries were decreased. In the offsprings' hippocampus of the CIS group, the chromatin of the nucleus was edge set and with condensed and irregular morphology nucleus, and the cytoplasm was unevenly stained with spaces around the cells, moreover, the expression levels of BDNF, NR2A, and NR2B were also declined (P < 0.05). However, Chaihu Shugan San reversed these changes, especially the BDNF in the DG region (P < 0.05), and NR2A and NR2B in the CA3 and DG region (P < 0.05). CONCLUSIONS: CSS could ameliorate the neural development of the hippocampus in offspring damaged by anxiety-like progestational stress in female rats via regulating the expression levels of ERα, ERß, and PR in female rat ovaries and BDNF, NR2A, and NR2B in the hippocampus of their offspring.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Extratos Vegetais/farmacologia , Efeitos Tardios da Exposição Pré-Natal , Receptores de N-Metil-D-Aspartato/metabolismo , Estresse Psicológico/tratamento farmacológico , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Modelos Animais de Doenças , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Feminino , Idade Gestacional , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Ovário/efeitos dos fármacos , Ovário/metabolismo , Gravidez , Ratos Wistar , Receptores de N-Metil-D-Aspartato/genética , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Restrição Física , Transdução de Sinais , Estresse Psicológico/genética , Estresse Psicológico/metabolismo , Estresse Psicológico/patologia
9.
Aging (Albany NY) ; 13(5): 7084-7095, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33638949

RESUMO

Polycystic ovarian syndrome (PCOS) is one of the most common reproductive endocrine disorders which are involved in complicated and unknown pathogenic mechanisms. Paeoniflorin (PAE) plays a significant anti-fibrotic role according to previous studies. The aim of the present study was to investigate the effect of PAE on ovarian fibrosis and its underlying mechanism in PCOS development. An animal model of PCOS was established by subcutaneous injection of 60mg/kg/d dehydroepiandrosterone (DHEA) for 35 consecutive days. Rats in PAE-L, PAE-M and PAE-H groups were administrated by gavage with PAE (20, 40, 80 mg/kg/d) for 4 weeks. Our results indicated that DHEA-induced PCOS rats showed similar phenotypes with PCOS patients. PAE could significantly block the DHEA-induced decline of ovary weight and organ coefficient, shorten the prolonged diestrus period, and regulate the irregular estrous cycle of PCOS rats. Moreover, PAE regulated reproductive hormone levels and improved ovarian fibrosis induced by DHEA. PAE treatment could also reduce the expression levels of TGF-ß1 and Smad3, and increase the expression levels of Smad7 and MMP2. In conclusion, PAE significantly attenuated the ovarian fibrosis in PCOS, which could be mediated by TGF-ß1/Smads signaling pathway. Herein, PAE can be used for the treatment of ovarian fibrosis in PCOS progression.


Assuntos
Glucosídeos/uso terapêutico , Monoterpenos/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Desidroepiandrosterona/farmacologia , Modelos Animais de Doenças , Ciclo Estral/efeitos dos fármacos , Feminino , Ovário/efeitos dos fármacos , Ovário/metabolismo , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Ratos , Ratos Sprague-Dawley
10.
Ecotoxicol Environ Saf ; 212: 112012, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33550074

RESUMO

Microplastics (MPs) considered as a new persistent environmental pollutant could enter into the circulatory system and result in decrease of sperm quantity and quality in mice. However, the effects of Polystyrene MPs (PS MPs) on the ovary and its mechanism in rats remained unclear. In this present study, thirty-two healthy female Wistar rats were exposed to different concentrations of 0.5 µm PS MPs dispersed in deionized water for 90 days. Using hematoxylin-eosin (HE) staining, the number of growing follicles was decreased compared to the control group. In addition, the activity of glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) were decreased while the expression level of malondialdehyde (MDA) was increased in ovary tissue. Confirmed by immunohistochemistry, the integrated optical density of NLRP3 and Cleaved-Caspase-1 had been elevated by 13.9 and 14 in granulosa cells in the 1.5 mg/kg/d group. Furthermore, compared to the control group, the level of AMH had been decreased by 23.3 pg/ml while IL-1ß and IL-18 had been increased by 32 and 18.5 pg/ml in the 1.5 mg/kg/d group using the enzyme-linked immune sorbent assay (ELISA). Besides, the apoptosis of granulosa cells was elevated measured by terminal deoxyribonucleotide transferase-mediated nick end labeling (TUNEL) staining and flow cytometry. Moreover, western blot assays showed that the expressions of NLRP3/Caspase-1 signaling pathway related factors and Cleaved-Caspase-3 were increased. These results demonstrated that PS MPs could induce pyroptosis and apoptosis of ovarian granulosa cells via the NLRP3/Caspase-1 signaling pathway maybe triggered by oxidative stress. The present study suggested that exposure to microplastics had adverse effects on ovary and could be a potential risk factor for female infertility, which provided new insights into the toxicity of MPs on female reproduction.


Assuntos
Apoptose/efeitos dos fármacos , Caspase 1/metabolismo , Microplásticos/toxicidade , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ovário/efeitos dos fármacos , Poliestirenos/toxicidade , Piroptose/efeitos dos fármacos , Animais , Feminino , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Células da Granulosa/patologia , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Malondialdeído/metabolismo , Ovário/metabolismo , Ovário/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Transdução de Sinais
11.
Biomed Res Int ; 2021: 6660087, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33623786

RESUMO

Background: More than a third of women could develop ovarian cysts during their lifetime. Jingshu granules are used for the treatment of gynecological disease of primary dysmenorrhea. However, the molecular mechanisms of Jingshu granules in ovarian cysts are still unreported. We aimed to find the active ingredients, molecular targets, and potential signaling pathways of Jingshu granules in ovarian cysts by using the systemic pharmacological analysis. Methods: Firstly, the effect of Jingshu granules on female hormones and reproductive organs of young female rats was evaluated. Secondly, candidate pharmaceutical ingredients of Jingshu granules were retrieved from the traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform. Potential protein targets for the active ingredients in Jingshu granules were then identified according to the oral bioavailability and drug-likeness indices. Thirdly, ovarian cyst-related gene targets were screened based on different databases. Finally, enrichment analysis was used to analyze the potential biological function of intersection targets between Jingshu granules and ovarian cysts. Results: In young female rats, Jingshu granules reduced the secretion of estradiol, progesterone, and prolactin and could affect the development of the uterus. This suggested that Jingshu granules played roles in hormone secretion and reproduction. From the TCMSP, a total of 1021 pharmaceutical ingredients of Jingshu granules were retrieved. After further screening, a total of 166 active ingredients and 159 protein targets of Jingshu granules were identified. In addition, 4488 gene targets of ovarian cysts were screened out. After taking the intersection, a total of 110 intersection targets were identified between potential protein targets of Jingshu granules and gene targets of ovarian cysts. In the functional analysis of 110 intersection targets, 8 signaling pathways including progesterone-mediated oocyte maturation (MAPK8 and CDK1 involved), GnRH signaling pathway (JUN involved), T cell receptor signaling pathway and Toll-like receptor signaling pathway (MAPK1 involved), NOD-like receptor signaling pathway (TNF, IL6, and IL1B involved), p53 signaling pathway (CDK2 and CDK4 involved), VEGF signaling pathway (MAPK14 involved), and PPAR signaling pathway (PPARG involved) were obtained. Conclusion: Our study revealed that Jingshu granules could function in patients with ovarian cysts through a number of molecular targets and signaling pathways. Our study may provide a new field into the mechanisms of Jingshu granules in ovarian cysts, from the molecular to the signaling pathway level.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Cistos Ovarianos/metabolismo , Ovário/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Estrogênios/metabolismo , Feminino , Ovário/metabolismo , Ratos , Ratos Sprague-Dawley
12.
Chem Biol Interact ; 338: 109402, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33587916

RESUMO

Cisplatin is an important antineoplastic drug used in multiple chemotherapeutic regimens but unfortunately causes serious toxic effects as ovarian and uterine toxicity. This study aimed to investigate the potential protective effect of resveratrol (RSV) against cisplatin-induced ovarian and uterine toxicity in female rats. Thirty-two female Wistar rats were divided randomly into four groups (n = 8 in each). Control group received oral normal saline for 28 days; RSV group received RSV (10 mg/kg; daily) via oral gavage; CIS group received a single dose of CIS (7 mg/kg; i.p.) on the 21st day; (CIS + RSV) group received both RSV and CIS by the same schedules and doses of RSV and CIS groups, respectively. Results demonstrated a significant decrease in MDA level and a significant increase in both glutathione content and activity of the antioxidant enzymes GPx, SOD, and CAT in the tissues of the ovary and uterus of CIS + RSV group in comparison to that of CIS group (P<0.05), also there are significantly decreased tissue levels of the proinflammatory cytokines and enzymes (NF-κB, IL-1ß, IL-6, TNF-α, COX-2, and iNOS), increased estradiol, progesterone, prolactin and decreased FSH serum levels in CIS + RSV group compared to CIS group (P < 0.05). Moreover, there is downregulation of tissues Cleaved Caspase-3, NF-κB and Cox-2 proteins as shown in Western blot analysis, also apoptosis was significantly inhibited, evidenced by downregulation of Bax and upregulation of Bcl-2 proteins, and the ovarian and uterine histological architecture and integrity were maintained in CIS + RSV group compared to CIS group. In conclusion, these findings indicate that RSV has beneficial effects in ameliorating cisplatin-induced oxidative stress, inflammation, and apoptosis in the ovarian and uterine tissues of female rats.


Assuntos
Apoptose/efeitos dos fármacos , Cisplatino/efeitos adversos , Inflamação/patologia , Ovário/patologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Resveratrol/farmacologia , Útero/patologia , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Catalase/metabolismo , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Malondialdeído/metabolismo , Modelos Biológicos , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ovário/efeitos dos fármacos , Progesterona/sangue , Prolactina/sangue , Carbonilação Proteica/efeitos dos fármacos , Ratos Wistar , Superóxido Dismutase/metabolismo , Proteína X Associada a bcl-2/metabolismo
13.
Eur J Endocrinol ; 184(5): R177-R192, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33630753

RESUMO

Fertility and ovarian protection against chemotherapy-associated ovarian damage has formed a new field called oncofertility, which is driven by the pursuit of fertility protection as well as good life quality for numerous female cancer survivors. However, the choice of fertility and ovarian protection method is a difficult problem during chemotherapy and there is no uniform guideline at present. To alleviate ovarian toxicity caused by anticancer drugs, effective methods combined with an individualized treatment plan that integrates an optimal strategy for preserving and restoring reproductive function should be offered from well-established to experimental stages before, during, and after chemotherapy. Although embryo, oocyte, and ovarian tissue cryopreservation are the major methods that have been proven effective and feasible for fertility protection, they are also subject to many limitations. Therefore, this paper mainly discusses the future potential methods and corresponding mechanisms for fertility protection in chemotherapy-associated ovarian damage.


Assuntos
Antineoplásicos/efeitos adversos , Preservação da Fertilidade/métodos , Infertilidade Feminina/induzido quimicamente , Infertilidade Feminina/prevenção & controle , Antineoplásicos/uso terapêutico , Feminino , Preservação da Fertilidade/tendências , Humanos , Neoplasias/tratamento farmacológico , Reserva Ovariana/efeitos dos fármacos , Ovário/efeitos dos fármacos , Ovário/fisiologia , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/prevenção & controle , Insuficiência Ovariana Primária/terapia
14.
Artigo em Inglês | MEDLINE | ID: mdl-33418082

RESUMO

Since nano-quantum dots (QDs) are increasingly used as fluorescent dyes in biomedical sciences, the possibility of QDs contaminating aquatic environments is generally increasing. There is concern about potential toxicity of QDs. However, their risks in the aquatic environment are not entirely understood. In this study, the freshwater crab Sinopotamon henanense was exposed to cadmium telluride (CdTe) QDs by intraperitoneal injection to detect the reproductive toxicity of QDs (1/32, 1/16 and 1/4 LD50; Crab was exposed for 1, 3, 5, and 7 days). After CdTe QD exposure, no significant effect was detected on the body weight and gonadosomatic index. Additionally, morphological observations showed tissue vacuolation in the testis, and inflammatory cell infiltration in the ovary. The submicroscopic structure showed that exposure to CdTe QDs damaged the organelles and cell structures of the gonads of S. henanense. Among the adverse effects, pathological changes in the nuclear membrane, mitochondria and lysosomes were particularly significant. Antioxidant enzymes responded differently to different doses of QDs. The 0.5-mg/kg dose induced superoxide dismutase activity in the testes. And in the 1-mg/kg and 4-mg/kg dose QD exposure test, the testis responded by activating glutathione peroxidase and inducing reduced glutathione and overconsuming glutathione peroxidase. Respectively, the ovaries responded by overconsuming superoxide dismutase and glutathione peroxidase and reduced glutathione. Thus, we conclude that the gonads of S. henanense were injured by CdTe QD, and male are better indicators of the toxicity of QDs than female crabs according to greater alterations in tissue structure and antioxidant enzyme in the analyses.


Assuntos
Braquiúros , Compostos de Cádmio/toxicidade , Ovário/efeitos dos fármacos , Pontos Quânticos/química , Telúrio/toxicidade , Testículo/efeitos dos fármacos , Animais , Compostos de Cádmio/química , Feminino , Glutationa/metabolismo , Dose Letal Mediana , Peróxidos Lipídicos , Masculino , Pontos Quânticos/toxicidade , Reprodução , Telúrio/química
15.
Ecotoxicol Environ Saf ; 208: 111566, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396095

RESUMO

Androgens and estrogens often co-exist in aquatic environments and pose potential risks to fish populations. However, little is known about the endocrine disrupting effects of the mixture of androgens and estrogens in fish. In this study, transcriptional level of target genes related to the hypothalamic-pituitary-gonadal-liver (HPGL) axis, sex hormone level, VTG protein concentration, histology and secondary sex characteristic were assessed in the ovaries and livers of adult female western mosquitofish (Gambusia affinis) exposed to 17ß-estradiol (E2), testosterone (T), and mixtures of E2 and T for 91 days. The results showed that the transcriptional expression of cytochrome P450, family 19, subfamily A, polypeptide 1a (Cyp19a1a) was suppressed in the 200 ng/L T treatment and the 50 ng/L E2 + 200 ng/L T treatment in the ovaries. Steroidogenic acute regulatory protein (Star) and Cyp11a1 showed a similar expression pattern in the T treatment to its corresponding T + E2 mixtures. In the ovaries, the concentrations of 17ß-estradiol and testosterone were decreased in most treatments compared with the solvent control. VTG protein was induced in all steroid treatment. However, exposure to T or E2 + T mixture did not cause the abnormal cells of the ovaries and livers and an extension of the anal fins in female G. affinis. This study demonstrates that chronic exposure to E2, T and their mixtures affects the transcripts of genes in the HPGL axis, steroid hormone level and VTG protein concentration in the ovaries and livers, but fails to cause the histopathological effect of the ovaries and livers and alter the morphology of the anal fins in G. affinis.


Assuntos
Ciprinodontiformes/fisiologia , Disruptores Endócrinos/toxicidade , Estradiol/toxicidade , Androgênios/metabolismo , Animais , Ciprinodontiformes/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Disruptores Endócrinos/metabolismo , Estradiol/metabolismo , Estrogênios/metabolismo , Feminino , Hormônios Esteroides Gonadais/metabolismo , Fígado/efeitos dos fármacos , Masculino , Ovário/efeitos dos fármacos , Testosterona/metabolismo , Vitelogeninas/metabolismo
16.
Toxicol Appl Pharmacol ; 413: 115409, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33476676

RESUMO

There is increasing evidence that bisphenols BPS and BPF, which are analogues of BPA, have deleterious effects on reproduction even at extremely low doses. Indirect exposure via the maternal route (i.e. across the placenta and/or by breastfeeding) is underestimated, although it can be assumed to be a cause of idiopathic female infertility. Therefore, we hypothesised the deleterious effects of exposure to BPA analogues during breastfeeding on the ovarian and oocyte quality of offspring. A 15-day exposure period of pups was designed, whilst nursing dams (N ≥ 6 per experimental group) were treated via drinking water with a low (0.2 ng/g body weight/day) or moderate (20 ng/g body weight/day) dose of bisphenol, mimicking real exposure in humans. Thereafter, female pups were bred to 60 days and oocytes were collected. Immature oocytes were used in the in-vitro maturation assay; alternatively, in-vivo-matured oocytes were isolated and used for parthenogenetic activation. Both in-vitro- and in-vivo-matured oocytes were subjected to immunostaining of spindle microtubules (α-tubulin) and demethylation of histone H3 on the lysine K27 (H3K27me2) residue. Although very low doses of both BPS and BPF did not affect the quality of ovarian histology, spindle formation and epigenetic signs were affected. Notably, in-vitro-matured oocytes were significantly sensitive to both doses of BPS and BPF. Although no significant differences in spindle-chromatin quality were identified in ovulated and in-vivo-matured oocytes, developmental competence was significantly damaged. Taken together, our mouse model provides evidence that bisphenol analogues represent a risk to human reproduction, possibly leading to idiopathic infertility in women.


Assuntos
Compostos Benzidrílicos/toxicidade , Fertilidade/efeitos dos fármacos , Infertilidade Feminina/induzido quimicamente , Lactação/metabolismo , Leite/metabolismo , Oócitos/efeitos dos fármacos , Ovário/efeitos dos fármacos , Fenóis/toxicidade , Sulfonas/toxicidade , Animais , Animais Lactentes , Compostos Benzidrílicos/metabolismo , Epigênese Genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Maturação in Vitro de Oócitos , Infertilidade Feminina/metabolismo , Infertilidade Feminina/patologia , Infertilidade Feminina/fisiopatologia , Exposição Materna , Camundongos Endogâmicos ICR , Oócitos/metabolismo , Oócitos/patologia , Reserva Ovariana/efeitos dos fármacos , Ovário/metabolismo , Ovário/fisiopatologia , Fenóis/metabolismo , Gravidez , Medição de Risco , Fuso Acromático/efeitos dos fármacos , Fuso Acromático/metabolismo , Fuso Acromático/patologia , Sulfonas/metabolismo
17.
J Steroid Biochem Mol Biol ; 208: 105823, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33484844

RESUMO

Polycystic ovarian syndrome (PCOS) is a multi-factorial gynecological endocrine disorder. It affects fertility in women and also predisposes to insulin resistance, type 2 diabetes mellitus, obesity etc. Earlier, significance of autophagy has been explored in PCOS-related metabolic disorders and during normal folliculogenesis. Increasing evidences reveal connection of autophagy with chronic inflammatory behaviour, an associated phenomena in polycystic ovaries. However, understanding of the association of autophagy with PCOS is still obscure. This study reveals that increased autophagy in mifepristone (RU486) treated KK-1 cells and in vivo PCO rat model is characterized by upregulated Androgen Receptor (AR) expression and downregulated PCO biomarker aromatase. The prevalence of autophagy has been observed to be concomitant with increased expression of two autophagic markers Beclin1 and MAP-LC3-II while the autophagy substrate p62/SQSTM1 was downregulated. Immunohistochemical staining revealed increased localization of MAP-LC3 in the compacted granulosa layers of the follicular cysts in the PCO model. The PCO rat models also demonstrated augmented levels of p65, the active subunit of NF-κB, which acts as a transcriptional regulator of several pro-inflammatory factors. NF-κB repressor and anti-inflammatory herbal drug thymoquinone, known to alleviate PCO condition, downregulated autophagy modules substantially. Pre-treatment with thymoquinone upregulated aromatase, reduced AR levels and decreased autophagic markers as well as p65 levels, simulating super-ovulated condition. In conclusion, the anti-inflammatory phytochemical thymoquinone alleviated PCO condition.


Assuntos
Autofagia/efeitos dos fármacos , Benzoquinonas/farmacologia , Mifepristona/farmacologia , Síndrome do Ovário Policístico/tratamento farmacológico , Receptores Androgênicos/genética , Androgênios/metabolismo , Animais , Autofagia/genética , Proteína Beclina-1/genética , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células da Granulosa/efeitos dos fármacos , Humanos , Resistência à Insulina/genética , Ovário/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Ovulação/efeitos dos fármacos , Ovulação/genética , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/patologia , Ratos , eIF-2 Quinase/genética
18.
J Environ Sci Health B ; 56(1): 30-40, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33052060

RESUMO

Clarias gariepinus juveniles were exposed to environmentally relevant concentrations of 0 (control), 2.5, 25, 250 and 500 µg L-1 atrazine in a quality-controlled 28-day laboratory procedure. Findings revealed a significant decrease in the levels of follicle-stimulating hormone, luteinizing hormone and prolactin relative to control (p < 0.05). Atrazine reduced the levels of testosterone while increasing the concentration of progesterone. Histologically, the control and treatments presented three stages of oocyte maturation: the chromatin nucleolar oocyte stage, early perinucleolar oocyte stage and the vitellogenic oocyte stage. However, in the ovaries of the treatment group with the lowest treatment concentration (2.5 µg L-1), atretic oocytes with broken membranes invaded many of the dead ova and empty spaces. In other treatments (25, 250 and 500 µg L-1), interfollicular spaces, vacuolation in oocyte formation, and dissolution of oocyte walls were observed. Disruption of the yolk vesicle and clumping of the cytoplasm in maturing oocytes was observed only at the highest atrazine concentration (500 µg L-1). Gross alterations in ovarian histoarchitecture and reproductive hormone levels observed in this study showed interference with oogenesis which may result in reduced egg viability and fecundity in fish with ecological implications in water bodies exposed to atrazine even at reduced concentrations.


Assuntos
Atrazina/toxicidade , Peixes-Gato/fisiologia , Herbicidas/toxicidade , Oogênese/efeitos dos fármacos , Ovário/efeitos dos fármacos , Animais , Feminino , Hormônios Gonadais/metabolismo , Hormônio Luteinizante/metabolismo , Oócitos/efeitos dos fármacos , Oócitos/crescimento & desenvolvimento , Ovário/patologia
19.
Biochem Biophys Res Commun ; 534: 780-786, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33162031

RESUMO

Ovarian tissue cryopreservation and transplantation (OCT) has been sufficiently proven effective and feasible to preserve fertility for women especially for prepubertal girls suffering from cancer with radiotherapy and chemotherapy. However, grafts' survival, significant follicle loss and a delay of revascularization during OCT still need to be resolved no matter what kind of cryopreserved method being used. Different from previous reports about additives treatment on recipient after ovarian transplantation, we here report a new vitrification protocol with pretreatment of rapamycin, an inhibitor of the mTOR signaling pathway. The rapamycin treatment has been shown to inhibit the activation of mTOR signaling pathway in fresh thawed ovaries or in ovaries shortly grafted in the recipient mice. Further study revealed increased percentage of primordial follicles and reduced apoptosis after 5 days of transplantation. Long-term follow up of ovarian development demonstrated the increase of ovarian survival rates in rapamycin treated ovaries after 2 weeks of transplantation. Although follicular development showed a slight delay with more secondary and early antral follicles found in rapamycin treated ovaries, follicular development was not blocked as manifested by the ovarian morphology after 5 weeks of transplantation. Taken together, the pretreatment of rapamycin before vitrification is a good method for clinical application with its effectiveness on preserving follicle reserve and promoting ovarian survival during the process of OCT.


Assuntos
Criopreservação/métodos , Preservação de Órgãos/métodos , Ovário/efeitos dos fármacos , Ovário/transplante , Sirolimo/farmacologia , Animais , Apoptose/efeitos dos fármacos , Crioprotetores/farmacologia , Feminino , Camundongos Endogâmicos ICR , Transplante de Órgãos/métodos , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/patologia , Ovário/citologia , Serina-Treonina Quinases TOR/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-33148510

RESUMO

Methoprene-tolerant (Met) belongs to the basic helix-loop-helix (bHLH)-Per-Arnt-Sim (PAS) family of nuclear transcriptional regulators and is a leading candidate receptor for juvenile hormone (JH III) in insects. Methyl farnesoate (MF) is a de-epoxide form of JH III that regulates many developmental processes in crustaceans, including reproduction, molting, and morphogenesis, much like JH III in insects. In this study, the full-length cDNA for Met was cloned from the Chinese mitten crab (Eriocheir sinensis) (EsMet). The amino acid sequence of EsMet contains three conserved domains (bHLH, PAS-A, and PASB) characteristic of the bHLH-PAS family, having six conserved amino acid residues specifically responsible for JH or MF binding. Tissue distribution analysis revealed that EsMet mRNA is highly expressed in the hepatopancreas. In addition, EsMet and EsVg expression in the hepatopancreas were found to be significantly increased in early endogenous vitellogenic oocytes (stage II) during ovarian development, and the hemolymph MF titer was significantly increased in late exogenous vitellogenic oocytes (stage III), indicating that EsMet is involved in vitellogenesis regulation. In vitro, MF addition markedly upregulated EsMet and EsVg expression in hepatopancreatic tissue, but only EsVg was induced in ovarian tissue. In vivo, EsMet and EsVg expression in the hepatopancreas were both significantly and synchronously increased after MF injection, but not in the ovaries. In addition, EsMet and EsVg expression were upregulated in the hepatopancreas after eyestalk ablation, while only EsVg expression was induced in the ovaries. Thus, our results indicate that Met may act as a receptor for MF in MF-mediated vitellogenesis in crustaceans.


Assuntos
Braquiúros/fisiologia , Ácidos Graxos Insaturados/farmacologia , Metoprene/farmacologia , Sequência de Aminoácidos , Animais , Braquiúros/efeitos dos fármacos , Clonagem Molecular/métodos , DNA Complementar/genética , Feminino , Hemolinfa/efeitos dos fármacos , Hemolinfa/metabolismo , Hepatopâncreas/efeitos dos fármacos , Hepatopâncreas/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Filogenia , Reprodução , Vitelogênese
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...