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1.
Adv Exp Med Biol ; 1191: 523-541, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32002944

RESUMO

Exposure therapy, a key treatment for anxiety disorders, can be modelled in the laboratory using Pavlovian fear extinction. Understanding the hormonal and neurobiological mechanisms underlying fear extinction in females, who are twice more likely than males to present with anxiety disorders, may aid in optimising exposure therapy outcomes in this population. This chapter will begin by discussing the role of the sex hormones, estradiol and progesterone, in fear extinction in females. We will also propose potential mechanisms by which these hormones may modulate fear extinction. The second half of this chapter will discuss the long-term hormonal, neurological and behavioural changes that arise from pregnancy and motherhood and how these changes may alter the features of fear extinction in females. Finally, we will discuss implications of this research for the treatment of anxiety disorders in women with and without prior reproductive experience.


Assuntos
Transtornos de Ansiedade/metabolismo , Transtornos de Ansiedade/terapia , Ansiedade/metabolismo , Ansiedade/terapia , Estradiol/metabolismo , Progesterona/metabolismo , Reprodução , Ansiedade/psicologia , Transtornos de Ansiedade/psicologia , Extinção Psicológica , Medo , Feminino , Humanos , Gravidez
2.
Gene ; 732: 144350, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31935505

RESUMO

THO complex is a multisubunit family with a function in transcription and mRNA export. In the present study, transcripts of THO complex (thoc) were identified in developing ovary of common carp and their role during ovarian development and growth has been characterized for the first time in a teleost using expression profiling and transient siRNA silencing. Thoc expression revealed a spatiotemporal pattern in the gonads with high levels at 120 days post-hatch, with moderately high levels thereafter. In situ hybridization and immunohistochemical localization revealed the presence of thoc3 in follicular layer of stage-III/IV oocytes. High levels of thoc3, thoc5, and thoc7 genes in the follicular layer suggest a possible role in ovarian growth. Reduced levels of serum estradiol-17ß and 17α, 20ß-dihydroxypregn-4-en-3-one after thoc3 transient silencing indicated differential action on steroidogenic enzyme, transcription factor, and growth factor genes. Furthermore, transient silencing of thoc3, in vivo and in vitro, downregulated ad4bp/sf1, amh, cyp19a1a, foxl2, hsd3b, hsd11b1, hsd20b, hsd17b1, rspo1, and vtg. Incidentally, gdf9 and igf1 were upregulated, while no change was seen in esr1/2, nanos, and vasa. These observations imply that thoc3 seems to regulate ovarian function including steroidogenesis, either directly or indirectly.


Assuntos
Carpas/genética , Perfilação da Expressão Gênica/veterinária , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Ovário/crescimento & desenvolvimento , Animais , Núcleo Celular/genética , Estradiol/metabolismo , Evolução Molecular , Feminino , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Folículo Ovariano , Ovário/química , RNA Interferente Pequeno/farmacologia , Diferenciação Sexual
3.
Life Sci ; 240: 117085, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759042

RESUMO

AIMS: Our study was designed to explore the function and mechanism of Tanshinone IIA in alleviating pain syndrome caused by endometriosis (EMs). MAIN METHODS: Female Sprague-Dawley rats went through autotransplantation operation to establish EMs model. The rats were randomly divided into five groups: sham, model, positive, Tanshinone IIA (L) (3 mg/kg/d) and Tanshinone IIA (H) (12 mg/kg/d) group. Volume of ectopic endometrium was measured after 21 days of continuous administration. Serum estradiol (E2) was detected by enzyme linked immunosorbent assay (Elisa). The protein expression of angiotensinogen (AGT), renin (REN), angiotensin converting enzyme (ACE), angiotensin II (ANGII) and angiotensin II type 2 receptor (AT2) in the dorsal root ganglion (DRG) neurons were measured by immunohistochemistry and Western Blotting. The mRNA expression levels of AGT and ANGII were measured by Real-time polymerase chain reaction (PCR). KEY FINDINGS: Tissue measurements showed that tanshinone IIA significantly inhibited the growth of ectopic endometrium. Tanshinone IIA could improve the paw withdrawal threshold thus reducing the mechanical hyperalgesia of EMs rats. Moreover, Tanshinone IIA regulated the DRG renin angiotensin system (RAS) by reducing the protein expression of AGT, REN, ACE, ANGII and AT2 in DRG neurons. Furthermore, Real-time PCR results also showed that the mRNA expression levels of AGT and ANGII in the DRG neurons were decreased. SIGNIFICANCE: The Tanshinone IIA inhibitory effect on the EMs associated pain in EMs rats might occur through decreasing the expression of E2, ANGII and AT2, thus halting DRG sprouting and promoting hyperalgesia threshold.


Assuntos
/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Axônios/patologia , Endometriose/tratamento farmacológico , Gânglios Espinais/patologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Angiotensina II/metabolismo , Animais , Endometriose/patologia , Estradiol/metabolismo , Feminino , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Ratos , Ratos Sprague-Dawley
4.
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
5.
Chemosphere ; 240: 124935, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31563720

RESUMO

Increasing studies have established the toxic effects of BPA on development and reproduction in animals. In present study, we investigated epigenetic effects on the transcription of several ovarian steroidogenic genes in rare minnows Gobiocypris rarus after BPA exposure at 15 µgL-1 for 21, 42 and 63 d. Results showed that short term BPA exposure (21 d) caused significant increase of both estradiol and testerone levels whereas long term exposure (63 d) led to significant decrease of them. The oocytes development was hindered after BPA exposure. BPA treatments for 21 and 42 d resulted in significant increase of genome DNA methylation in ovary while 63-d exposure caused marked decrease. The histone trimethylation levels (H3K4me3, H3K9me3 and H3K27me3) in the ovary were also disturbed by BPA. H3K9me3 was significantly decreased after 21 d whereas it was markedly increased after 42 and 63 d. The 42-d exposure caused significant decrease for H3K4me3. Meanwhile, 42- and 63-d BPA exposure led to significant decrease of H3K27me3. DNA methylation could involve in gene expression regulation of cyp17a1 and cyp19a1a after BPA exposure. After short (21 d) and long term (63 d) BPA exposure, the respective mRNA expression down-regulation and up-regulation of star, cyp11a1, and cyp17a1 were mediated by H3K9me3. This study suggests that epigenetic modulation including DNA and histone methylation could be responsible for the detrimental effects on ovary development upon BPA exposure in G. rarus. It is speculated that BPA exposures for short or long term duration could disturb the steroidogenesis in entirely different mechanisms.


Assuntos
Compostos Benzidrílicos/toxicidade , Cyprinidae/genética , Metilação de DNA/efeitos dos fármacos , Estrogênios não Esteroides/toxicidade , Oócitos/crescimento & desenvolvimento , Ovário/crescimento & desenvolvimento , Fenóis/toxicidade , Animais , Cyprinidae/metabolismo , DNA/metabolismo , Estradiol/metabolismo , Feminino , Regulação da Expressão Gênica , Histonas/genética , Diferenciação Sexual/efeitos dos fármacos , Esteroide 17-alfa-Hidroxilase/genética , Testosterona/metabolismo
6.
Life Sci ; 242: 117207, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31863777

RESUMO

Abdominal Aortic Aneurysm (AAA) is a severe cardiovascular disease, with high mortality rate after acute rupture of blood vessels. However, the underlying pathogenesis of different morbidity between men and women remains unclear. In the present study, we first selected four datasets including 68 AAA and 32 control samples from published data on GEO database, and analyzed them by data mining. The integrative analysis found a total of 368 differentially expressed genes in E2-related AAA. Next, regulatory mechanism networks among these target genes were predicted, and four genes were identified as key nodes in the network, which play a major role in the immune system. We focused on the role of monocytes/macrophages in the development of cardiovascular diseases to further explore the role of estrogen in the polarization of monocytes/macrophage, the mRNA level of the four genes was validated by RT-PCR in RAW264.7 cells treated with ß-estradiol (E2), diarylpropionitrile (DPN), 1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT), fulvestrant or vehicle. The results showed that the mRNA level and protein level of TROVE2 was significantly increased in estrogen or estrogen receptor agonist-treated groups. Moreover, estrogen affected the transformation of macrophages to M2 phenotype by detecting M1- and M2-related indicator genes at the mRNA level. Flow cytometry demonstrated that the TROVE2 deficiency led to a notable decrease in the level of M2 phenotype marker protein CD206. In conclusion, our results suggest that E2 can promote the expression of TROVE2, which is closely related to the M2-phenotype transformation of macrophages.


Assuntos
Aneurisma da Aorta Abdominal/fisiopatologia , Autoantígenos/fisiologia , Estradiol/metabolismo , Ativação de Macrófagos , RNA Citoplasmático Pequeno/fisiologia , Ribonucleoproteínas/fisiologia , Animais , Aneurisma da Aorta Abdominal/metabolismo , Autoantígenos/metabolismo , Western Blotting , Estradiol/fisiologia , Citometria de Fluxo , Humanos , Camundongos , Células RAW 264.7 , RNA Citoplasmático Pequeno/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Ribonucleoproteínas/metabolismo , Transcriptoma
7.
Environ Sci Process Impacts ; 22(1): 197-206, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31841122

RESUMO

17ß-estradiol (E2) ubiquitously exists in various water bodies with long-term endocrine-disrupting and carcinogenic impacts on wildlife even at the trace level of ng L-1. However, it remains unclear how easy-to-degrade carbon sources alter E2 biodegradation patterns. In this study, E2 biodegradation by Sphingomonas sp. MCCC 1A06484 was investigated with regard to alternative carbon sources. Results showed that the bacterium preferentially utilized glucose, sodium succinate and sodium acetate over E2. Interestingly, the presence of these preferred nutrients increased the E2 removal efficiency by 20.1%. Furthermore, a positive relation (p < 0.05) between the utilization of total organic carbon (TOC) and E2 was found. Using intracellular metabolomics by UHPLC-QTOF-MS, 11 up-regulated and 35 down-regulated metabolites (variable importance > 1, p < 0.05) were identified in the bacterium when cultivated with E2 under various carbon and nitrogen backgrounds. The E2 exposure contributed to metabolism changes of lipid, nucleotide, carbohydrate, amino acid and membrane transport, which were considered to play roles in the E2 metabolism. The up-regulated phosphatidylcholine might act as an indicator during the bacterial degradation of E2. Generally, this study contributes to an in-depth understanding of E2 biodegradation in complex environments with multiple carbon and nitrogen sources.


Assuntos
Estradiol , Metabolômica , Sphingomonas , Poluentes Químicos da Água , Biodegradação Ambiental , Carbono , Estradiol/metabolismo , Sphingomonas/metabolismo , Poluentes Químicos da Água/metabolismo
8.
Chemosphere ; 240: 124900, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31563099

RESUMO

Spirotetramat (SPT) is a new tetronic acid derivative insecticide used to control scales and aphids; the potential for endocrine disruptor effects in fish could not be finalized with the available data. In this study, zebrafish were selected to assess the endocrine-disrupting effects. Significant decrease of plasma estradiol (E2), testosterone (T) and 11-ketotestosterone (11-KT) were observed in both male and female following the spirotetramat exposure; the vitellogenin (VTG) level in females significantly decreased. The expression of the hypothalamic-pituitary-gonad (HPG) axis genes fshr, lhr and esr1 showed significant increase in the gonads, which expression in males is higher than in females. In addition, the activities of capspase-3 and caspase-9 significantly decreased in both males and females liver, while the capspase-3 and caspase-9 were increased in male testis, the mRNA expression levels of genes expression related to the apoptosis pathway were also significantly altered after the spirotetramat exposure. Additionally, we found the parental zebrafish exposed to spirotetramat induced the development delay of its offspring. Above all, the adverse effects induced by spirotetramat suggesting that spirotetramat is a potential exogenous hazardous agent.


Assuntos
Compostos Aza/toxicidade , Inseticidas/toxicidade , Compostos de Espiro/toxicidade , Animais , Apoptose , Disruptores Endócrinos/toxicidade , Estradiol/metabolismo , Estrogênios/farmacologia , Feminino , Expressão Gênica , Gônadas/efeitos dos fármacos , Fígado/metabolismo , Masculino , Testículo/efeitos dos fármacos , Testosterona/análogos & derivados , Vitelogeninas/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo
9.
Aquat Toxicol ; 217: 105335, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31706209

RESUMO

One of the categories of environmental contaminants possibly contributing to declining sockeye salmon (Oncorhynchus nerka) in the Fraser River, British Columbia, Canada is pesticides. In this 4-month study, the effects of environmentally relevant concentrations of a waterborne neonicotinoid, clothianidin (0.15, 1.5, 15 and 150 µg/L), on embryonic, alevin and early swim-up fry sockeye salmon derived from four unique genetic crosses of the Pitt River, BC stock were investigated. There were no significant effects of clothianidin on survival, hatching, growth or deformities, although genetic variation significantly affected these endpoints. Clothianidin caused a significant 4.7-fold increase in whole body 17ß-estradiol levels in swim-up fry after exposure to 0.15 µg/L, but no effects were observed on testosterone levels. In addition, hepatic expression of the gene encoding glucocorticoid receptor 2 was also impacted at the highest concentration of clothianidin tested, and was found to be ∼4-fold lower compared to the sockeye reared in control water. These results indicate additional examination of clothianidin and its effects on salmonid gonad development and the reproductive and stress endocrine axes in general, is warranted.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Guanidinas/toxicidade , Neonicotinoides/toxicidade , Rios/química , Salmão/crescimento & desenvolvimento , Tiazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Migração Animal/efeitos dos fármacos , Animais , Colúmbia Britânica , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/crescimento & desenvolvimento , Estradiol/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Fígado/metabolismo , Receptores de Glucocorticoides/genética , Reprodução/efeitos dos fármacos , Salmão/metabolismo , Natação
10.
Eat Behav ; 35: 101337, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31726420

RESUMO

OBJECTIVE: Eating disorder symptoms change in a predictable pattern over the menstrual cycle such that changes in symptoms are triggered by changes in the ovarian hormones estradiol (E2) and progesterone (P4). To date, work in this area has focused exclusively on young adult women. The objective of this pilot study was to examine the effect of E2 and P4 on eating disorder symptom change in midlife women during early perimenopause. METHOD: Participants included women aged 42-52 in early perimenopause (n=8). In-home self-assessments were completed for one menstrual cycle or 40-days, whichever occurred first. In-home self-assessments included collecting saliva samples each morning for E2 and P4 assays and completing online study questionnaires at the end of each day. Multilevel regression models examined the associations of E2 and P4 with daily symptoms of binge eating and body dissatisfaction. RESULTS: E2 was positively associated with binge eating when P4 was high, but not when P4 was low. E2 was inversely associated with body dissatisfaction when P4 was low, but positively associated with body dissatisfaction when P4 was high. However, the simple slopes for the effect of E2 at both high and low P4 were not significant for body dissatisfaction. CONCLUSIONS: Despite the pilot nature of this study, results are broadly consistent with the young adult literature indicating that P4 levels shape the impact of E2 on eating disorder symptoms. Larger studies with the inclusion of key moderators to account for individual heterogeneity are needed to confirm and extend these findings.


Assuntos
Bulimia/metabolismo , Estradiol/metabolismo , Menopausa/fisiologia , Ovário/metabolismo , Progesterona/metabolismo , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto
11.
Life Sci ; 239: 117082, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31756345

RESUMO

AIM: Investigating the impact of 17ß-Estradiol/estrogen receptors in gentamicin-induced nephrotoxicity. MAIN METHODS: Three weeks post-ovariectomy or sham surgery for the Wistar albino female rats, thirty sham rats were randomly grouped (n = 6), received either vehicle or gentamicin; the estrogen receptors down regulator (fulvestrant); gentamicin plus fulvestrant; gentamicin plus the phytoestrogen (genistein). Forty-eight ovariectomized rats were randomly grouped (n = 6), treated with either vehicle or gentamicin; fulvestrant; gentamicin plus fulvestrant; genistein; gentamicin plus genistein; estradiol benzoate; gentamicin plus estradiol benzoate. Just post-treatment termination, the traditional kidney injury biomarkers (serum creatinine and blood urea nitrogen) and novel biomarkers (serum Kidney injury molecule -1, cystatin C, lactate dehydrogenase and, gamma-glutamyl transferase) were determined. Bovine serum albumin labeled with fluorescence isothiocyanate assessed megalin expression/endocytic functionality in the proximal tubules epithelial cells (PTECs). The immunohistochemical investigation for the same-sectioned slides of PTECs assessed the correlation between estrogen receptors α and megalin receptors expression. Histopathological examination of PTECs and subjective scoring system graded the damage markers. KEY FINDINGS: Estrogen receptor α expression was markedly dimensioned post-ovariectomy, co-localized and inversely correlated to megalin expression. Serum levels of the novel biomarkers were directly proportional to megalin expression in the PTECs and inversely correlated with estrogen receptor α expression. The injury was exaggerated in ovariectomized and intact rats received fulvestrant. Supplementation with estrogen or genistein ameliorated this injury. SIGNIFICANCE: Estrogen/estrogen receptors have a protective impact on gentamicin-induced acute kidney injury. Estrogen receptors antagonist exacerbate the injury, and oppositely, estrogens or phytoestrogens improve it.


Assuntos
Lesão Renal Aguda/metabolismo , Estrogênios/metabolismo , Receptores Estrogênicos/metabolismo , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/patologia , Lesão Renal Aguda/prevenção & controle , Animais , Estradiol/metabolismo , Receptor beta de Estrogênio/metabolismo , Estrogênios/fisiologia , Feminino , Fulvestranto/metabolismo , Genisteína/farmacologia , Gentamicinas/efeitos adversos , Gentamicinas/farmacologia , Rim/metabolismo , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Ovariectomia , Fitoestrógenos/farmacologia , Ratos , Ratos Wistar , Receptores Estrogênicos/fisiologia
12.
Mar Pollut Bull ; 145: 418-428, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31590805

RESUMO

Pollution threats Antarctica and scientists blame xenobiotics and anthropic activities. Yet little is known about their effect on Antarctic ichthyofauna. Accordingly, we investigated the endocrine system of male fish Notothenia rossii and N. coriiceps (Perciformes, Nototheniidae) collected during Austral summer. For N. rossii, hormone levels of estradiol, testosterone, and 11-ketotestosterone were higher in fish collected during March than those of January; whereas for N. coriiceps estradiol and androgens levels were higher and lower in March, respectively. Histological analysis of the testes showed an unrestricted lobular type with no pathological alterations. However, detection of vitellogenin-like in plasma and skin mucus were seen in 75% of N. coriiceps males and 7% of N. rossii males. This is the first report of mucus vitellogenin-like detection as a non-invasive biomarker of endocrine disruption in notothenioid males and settles a baseline for future studies of reproductive biology and endocrine disruption in Antarctic fishes.


Assuntos
Sistema Endócrino/metabolismo , Perciformes/fisiologia , Reprodução/efeitos dos fármacos , Poluentes da Água/toxicidade , Animais , Regiões Antárticas , Ecotoxicologia , Sistema Endócrino/efeitos dos fármacos , Monitoramento Ambiental , Estradiol/metabolismo , Feminino , Masculino , Perciformes/crescimento & desenvolvimento , Testosterona/análogos & derivados , Testosterona/metabolismo
13.
Environ Sci Process Impacts ; 21(10): 1736-1744, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31498354

RESUMO

Steroid estrogens (SEs), especially 17ß-estradiol (E2), can be a serious threat to the health of organisms. The removal of E2 from the natural environment is mainly carried out by microbial degradation partly mediated by biochar, which contains quinone structures. In this study, reed straw biochar samples made at four different heat treatment temperatures (HTTs) were used to mediate E2 microbial degradation by Shewanella oneidensis MR-1. The removal efficiency of E2 (95%) was highest in the presence of HTT - 500 °C biochar under anaerobic conditions after 120 h of microbial degradation. The effect of biochar on promoting microbial degradation was far more superior under anaerobic conditions than under aerobic conditions. The redox-activity and types of surface functional groups of biochar reveal that biochar can accept electrons generated by microorganisms in a timely manner. This mechanism promotes the metabolic process of cells and microbial degradation of E2 (exponential increase). Biochar particles rather than biochar-derived water-soluble organic compounds are responsible for this stimulating effect. These results highlight the impact that biochar has on microbial degradation of trace pollutants in a natural environment.


Assuntos
Carvão Vegetal/química , Estradiol/metabolismo , Shewanella/metabolismo , Poluentes Químicos da Água/metabolismo , Biodegradação Ambiental , Estradiol/análise , Estrogênios/metabolismo , Microscopia Eletrônica de Varredura , Oxirredução , Shewanella/efeitos dos fármacos , Acetato de Sódio/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Poluentes Químicos da Água/análise
14.
J Ovarian Res ; 12(1): 82, 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31472696

RESUMO

Polycystic ovary syndrome (PCOS) is an endocrine disease that is common in women in their reproductive period. Patients with this disease suffer from anovulation and hyperandrogenism. Ovulation induction with exogenous gonadotropin often causes ovarian hyperstimulation syndrome because many small antral follicles pause in their growth. Treatment with insulin sensitizers is reportedly effective for both anovulation associated with PCOS, and suppression of excessive follicular growth; however, the underlying mechanism of action remains unknown. Although pioglitazone is known as an insulin sensitizer, it also has a potent modulator of cell growth and apoptosis irrespective of insulin resistance. To clarify the effect of pioglitazone on follicular growth, we performed in vitro culture of murine preantral follicles. Secondary follicles (100-160 µm in diameter) isolated from 6-week-old ICR mice were individually cultured for 13 days. Culture conditions were as follows: 1) follicle-stimulating hormone (FSH; 33 mIU/mL; control), 2) FSH plus dihydrotestosterone (DHT; 500 ng/mL), 3) FSH plus pioglitazone (5 ng/mL), and 4) FSH plus DHT/pioglitazone. Survival rate and follicle diameter were evaluated, and concentrations of estradiol (E2) and vascular endothelial growth factor (VEGF) in culture media were measured. mRNA expression of various growth-promoting factors and Vegf within follicles were also assessed. Although no significant differences were observed with regard to survival rate, follicle diameters on day 13 were significantly different.Compared with the control group, the DHT group showed enhanced growth, while groups administered pioglitazone showed stagnation of the accelerated growth induced by DHT. Although DHT treatment enhanced the expression of bone morphogenetic protein 2 (Bmp2) mRNA, pioglitazone exposure suppressed induction of Bmp2 mRNA by DHT. Vegf mRNA and protein expression were also significantly reduced when pioglitazone was added to culture media containing DHT.Administration of pioglitazone negatively affected follicular growth and VEGF levels, which may suppress excessive follicular growth and prevent ovarian hyperstimulation syndrome.


Assuntos
Hipoglicemiantes/farmacologia , Folículo Ovariano/efeitos dos fármacos , Pioglitazona/farmacologia , Androgênios/farmacologia , Animais , Proteína Morfogenética Óssea 2/genética , Di-Hidrotestosterona/farmacologia , Estradiol/metabolismo , Feminino , Camundongos Endogâmicos ICR , Folículo Ovariano/crescimento & desenvolvimento , Folículo Ovariano/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
15.
Anim Sci J ; 90(11): 1444-1452, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31486226

RESUMO

The aim was to evaluate in female roe deer: (a) PAG mRNA relative abundance in endometrial uterine tissue for determination of the duration of embryonic diapause, (b) mRNA relative abundance of progesterone, estradiol, and prolactin (P4, E2, and PRL) receptors (PGR, ESR, and PRLR) during diapause and after implantation in the endometrium; (c) concentration of P4, E2, and PRL in the blood, and (d) a noninvasive method of hormone detection by measurement of P4 and E2 concentrations in feces. A total of fifteen individuals were obtained post mortem during hunting seasons and divided into three experimental groups (November, December, January). The results did not reveal mRNA relative abundance for PAGs in the endometrium or detectable PAG concentrations in the serum of all examined females. Concentration of PRL and mRNA relative abundance for PRLR long isoform in the endometrium was the highest in January (p < .01). mRNA relative abundance for PGR, P4 concentration in the endometrium, serum, and feces was the highest in January (p < .01). Endometrial origin PRL and P4 may be responsible for the termination of this process and pregnancy development after implantation.


Assuntos
Cervos/metabolismo , Cervos/fisiologia , Implantação do Embrião/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Endométrio/metabolismo , Estradiol/genética , Estradiol/metabolismo , Feminino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Gravidez , Progesterona/genética , Progesterona/metabolismo , RNA Mensageiro/metabolismo , Receptores da Prolactina/genética , Receptores da Prolactina/metabolismo
16.
Artigo em Inglês | MEDLINE | ID: mdl-31386905

RESUMO

Gonadotropin-releasing hormones (GnRH) regulate gonadal growth of teleosts. Benzo(a)pyrene (BaP) functions as a reproductive endocrine disruptor. Furthermore, endocrine regulation on brood pouch growth of Syngnathidaes is elusive. To better understand the role of GnRH in brood pouch growth and effects of BaP on reproductive endocrine in lined seahorse (Hippocampus erectus), gnrh2 and gnrh3 genes were identified. Results showed that lined seahorse GnRH2 and GnRH3 precursors included the conservative tripartite structure and their transcripts highly expressed in brain as other teleosts. Expression profiles of gnrh2 and gnrh3 transcripts were detected during brood pouch growth. Results indicated that brain gnrh2 transcripts remarkably increased at the middle-stage and late-stage of brood pouch growth, while brain gnrh3 transcripts significantly raised at the early-stage and middle-stage. These suggested that GnRH2 and GnRH3 regulated brood pouch growth at different stages. Short-term BaP exposure in lined seahorse was performed. Transcripts of gnrh2 and gnrh3 remarkably increased in females and males exposed to BaP. Besides, plasma 17-beta estradiol (E2) levels presented a reduced trend during female fish exposed to BaP. This revealed that BaP functioned as anti-estrogenic effects and it may result in high expression of gnrh mRNA. However, plasma 11-ketone testosterone (11-KT) levels showed an increased trend during male fish exposed to BaP. Taken together, these indicated interesting results of BaP on reproduction in each sex of seahorse. These observations contribute to provide novel information of regulation on brood pouch growth and effects of BaP on reproductive endocrine in Syngnathidaes.


Assuntos
Benzo(a)pireno/farmacologia , Estradiol/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Gônadas/metabolismo , Ácido Pirrolidonocarboxílico/análogos & derivados , Smegmamorpha/metabolismo , Testosterona/análogos & derivados , Animais , Feminino , Masculino , Ácido Pirrolidonocarboxílico/metabolismo , RNA Mensageiro/metabolismo , Reprodução/fisiologia , Testosterona/metabolismo
17.
J Assist Reprod Genet ; 36(9): 1823-1835, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31376104

RESUMO

PURPOSE: Vitrification is a well-accepted fertility preservation procedure for cryopreservation of oocytes and embryos but little is known regarding ovarian tissue, for which slow freezing is the current convention. The aim of the present study was to assess the efficiency of non-equilibrium vitrification compared to conventional slow freezing for ovarian cortex cryopreservation. METHODS: Using prepubertal sheep ovaries, the capacity of the tissue to sustain folliculogenesis following cryopreservation and in vitro culture was evaluated. Ovarian cortex fragments were cultured in wells for 9 days, immediately or after cryopreservation by conventional slow freezing or non-equilibrium vitrification in straws. During culture, follicular populations within cortex were evaluated by histology and immunohistochemistry for PCNA and TUNEL. Steroidogenic activity of the tissue was monitored by assay for progesterone and estradiol in spent media. RESULTS: No significant differences in follicle morphology, PCNA, or TUNEL labeling were observed between cryopreservation methods at the initiation of culture. Similar decreases in the proportion of primordial follicle population, and increases in the proportion of growing follicles, were observed following culture of fresh or cryopreserved ovarian tissue regardless of cryopreservation method. At the end of culture, PCNA and TUNEL-positive follicles were not statistically altered by slow freezing or vitrification in comparison to fresh cultured fragments. CONCLUSIONS: Overall, for both cryopreservation methods, the cryopreserved tissue showed equal capacity to fresh tissue for supporting basal folliculogenesis in vitro. Taken together, these data confirm that both non-equilibrium vitrification and slow-freezing methods are both efficient for the cryopreservation of sheep ovarian cortex fragments.


Assuntos
Criopreservação/métodos , Folículo Ovariano , Ovário/fisiologia , Animais , Estradiol/metabolismo , Feminino , Preservação da Fertilidade/métodos , Folículo Ovariano/citologia , Folículo Ovariano/fisiologia , Progesterona/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Puberdade , Ovinos , Técnicas de Cultura de Tecidos , Vitrificação
18.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1126-1127: 121765, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31434025

RESUMO

The goal of this study was to develop and validate a high-throughput UHPLC-MS/MS method for simultaneous quantitation of three estradiol metabolites namely estradiol 3-ß-D-glucuronide (E3G), estradiol 17-ß-D-glucuronide (E17G) and estradiol 3-sulfate (E3S) in cell culture medium to support the characterization of metabolic function of induced pluripotent stem cell (iPSC) derived hepatocytes. To achieve this goal, a simple protein precipitation method was used for sample cleanup. All the metabolites were separated chromatographically using a C-18 column where 10 mM ammonium acetate and acetonitrile was used in gradient flow for 4 min. The analytes were quantitated by triple quadrupole mass spectrometer with the use of isotopically labeled internal standard (IS). This method was validated as per the U.S Food and Drug Administration's Bioanalytical Method Validation, Guidance for Industry. Linearity for E3G and E17G was in the range of 2-1500 ng/mL whereas for E3S it was 0.3-500 ng/mL. Inter-day and intra-day accuracy and precision of this method were in the acceptable limits. In addition, multiple stability tests (freeze thaw, autosampler, water bath (37 °C), bench top and long term) were performed for all the metabolites in cell culture medium. All the metabolites were stable up to 3 freeze thaw cycles at -20 °C and - 80 °C, 48 h in autosampler, 24 h at 37 °C, 48 h at room temperature and 173 days at -20 °C. Extraction recoveries for the metabolites were reproducible and were in the range of 94-108%. This method was used to quantitate estradiol metabolites generated by iPSC hepatocytes in-vitro studies.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Estradiol , Hepatócitos/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Espectrometria de Massas em Tandem/métodos , Estradiol/análogos & derivados , Estradiol/análise , Estradiol/metabolismo , Células Hep G2 , Humanos , Modelos Lineares , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
Biosci Trends ; 13(4): 334-341, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31434815

RESUMO

Histone acetylation has recently been implicated in gene transcription and estradiol (E2) actions in the hypothalamus. This study aims to determine the involvement of histone acetylation in mediating E2-induced luteinizing hormone (LH) surge to understand the mechanism underlying LH surge dysfunction in female reproductive aging. Young and middle-aged female rats were ovariectomized (OVX) and treated with hormone or oil once per day for two days. At the time of the expected LH surge, blood samples were taken for LH assay. The anterior and posterior hypothalami were dissected, histone H3/H4 acetylation and histone deacetylases (HDACs) 4, -5, -10 and -11 protein expressions were measured using Western blotting. Our results show that in the young females, E2 markedly increased histone H3 acetylation while significantly reducing HDAC10 protein expression in the anterior hypothalamus. Notably, E2-induced alterations of histone H3 acetylation and HDAC10 in the anterior hypothalamus were absent in middle-aged females, associated with a reduced LH release. However, age alters histone H4 acetylation in both the anterior and posterior hypothalamus and significantly increased HDAC 4 and -5 protein expression in the anterior hypothalamus. Taken together, these data suggest that histone H3 acetylation in the anterior hypothalamus may mediate E2 regulation of LH surge and the process possibly through decreasing HDAC10. The missed responsiveness of histone H3 acetylation and HDAC10 expression to E2 in the anterior hypothalamus may contribute to LH surge failure that occurs in female reproductive aging.


Assuntos
Histonas/metabolismo , Hipotálamo Anterior/metabolismo , Hormônio Luteinizante/sangue , Acetilação , Fatores Etários , Animais , Estradiol/metabolismo , Estradiol/fisiologia , Feminino , Ratos , Ratos Sprague-Dawley
20.
Oncogene ; 38(43): 6913-6925, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31406251

RESUMO

Metastatic, antiestrogen resistant estrogen receptor α positive (ER+) breast cancer is the leading cause of breast cancer deaths in USA women. While studies have demonstrated the importance of the stromal tumor microenvironment in cancer progression and therapeutic responses, effects on the responses of ER+ cancers to estrogen and antiestrogens are poorly understood, particularly in the complex in vivo environment. In this study, we used an estrogen responsive syngeneic mouse model to interrogate how a COL1A1-enriched fibrotic ECM modulates integrated hormonal responses in cancer progression. We orthotopically transplanted the ER+ TC11 cell line into wild-type (WT) or collagen-dense (Col1a1tm1Jae/+, mCol1a1) syngeneic FVB/N female mice. Once tumors were established, recipients were supplemented with 17ß-estradiol (E2), tamoxifen, or left untreated. Although the dense/stiff environment in mCol1a1 recipients did not alter the rate of E2-induced proliferation of the primary tumor, it fostered the agonist activity of tamoxifen to increase proliferation and AP-1 activity. Manipulation of estrogen activity did not alter the incidence of lung lesions in either WT or mCol1a1 hosts. However, the mCol1a1 environment enabled tamoxifen-stimulated growth of pulmonary metastases and further fueled estrogen-driven growth. Moreover, E2 remodeled peritumoral ECM architecture in WT animals, modifying alignment of collagen fibers and altering synthesis of ECM components associated with increased alignment and stiffness, and increasing FN1 and POSTN expression in the pulmonary metastatic niche. These studies demonstrate dynamic interactions between ECM properties and estrogen activity in progression of ER+ breast cancer, and support the need for therapeutics that target both ER and the tumor microenvironment.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Receptor alfa de Estrogênio/metabolismo , Estrogênios/metabolismo , Matriz Extracelular/metabolismo , Animais , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Estradiol/metabolismo , Antagonistas de Estrogênios/farmacologia , Matriz Extracelular/efeitos dos fármacos , Feminino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Camundongos , Tamoxifeno/farmacologia , Microambiente Tumoral/efeitos dos fármacos
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