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1.
Int J Mol Sci ; 22(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34502044

RESUMO

Implantation consists of a complex process based on coordinated crosstalk between the endometrium and trophoblast. Furthermore, it is known that the microenvironment of this fetal-maternal interface plays an important role in the development of extravillous trophoblast cells. This is mainly due to the fact that tissues mediate embryonic signaling biologicals, among other molecules, prostaglandins. Prostaglandins influence tissue through several cell processes including differentiation, proliferation, and promotion of maternal immune tolerance. The aim of this study is to investigate the potential pathological mechanism of the prostaglandin E2 receptor 4 (EP4) in modulating extravillous trophoblast cells (EVTs) in unexplained recurrent marriage (uRM). Our results indicated that the expression of EP4 in EVTs was decreased in women experiencing uRM. Furthermore, silencing of EP4 showed an inhibition of the proliferation and induced apoptosis in vitro. In addition, our results demonstrated reductions in ß- human chorionic gonadotropin (hCG), progesterone, and interleukin (IL)-6, which is likely a result from the activation of the cyclic adenosine monophosphate (cAMP)- cAMP-dependent protein kinase A (PKA)-phosphorylating CREB (pCREB) pathway. Our data might provide insight into the mechanisms of EP4 linked to trophoblast function. These findings help build a more comprehensive understanding of the effects of EP4 on the trophoblast at the fetal-maternal interface in the first trimester of pregnancy.


Assuntos
Aborto Habitual/metabolismo , AMP Cíclico/metabolismo , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Transdução de Sinais , Trofoblastos/metabolismo , Aborto Habitual/patologia , Adulto , Apoptose , Linhagem Celular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Feminino , Gonadotropinas/metabolismo , Humanos , Interleucina-6/metabolismo , Pessoa de Meia-Idade , Gravidez , Progesterona/metabolismo
2.
Int J Mol Sci ; 22(18)2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34576245

RESUMO

Currently, infertility affects 8-12% of reproductive age couples worldwide, a problem that also affects women suffering from recurrent implantation failure (RIF). RIF is a complex condition resulting from many physiological and molecular mechanisms involving dynamic endometrium-blastocyst interaction. The most important are the endometrial receptivity process, decidualization, trophoblast invasion, and blastocyst nesting. Although the exact multifactorial pathogenesis of RIF remains unclear, many studies have suggested the association between hormone level imbalance, disturbances of angiogenic and immunomodulatory factors, certain genetic polymorphisms, and occurrence of RIF. These studies were performed in quite small groups. Additionally, the results are inconsistent between ethnicities. The present review briefly summarizes the importance of factors involved in RIF development that could also serve as diagnostic determinants. Moreover, our review could constitute part of a new platform for discovery of novel diagnostic and therapeutic solutions for RIF.


Assuntos
Implantação do Embrião/fisiologia , Endométrio/patologia , Infertilidade Feminina/genética , Adulto , Biomarcadores , Blastocisto , Endométrio/metabolismo , Estrogênios/metabolismo , Feminino , Glicodelina/metabolismo , Humanos , Sistema Imunitário , Fatores Imunológicos , Infertilidade Feminina/metabolismo , Fator Inibidor de Leucemia/metabolismo , Microbiota , Neovascularização Patológica , Progesterona/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Recidiva , Fatores de Risco , Vagina/microbiologia
3.
Life Sci ; 285: 119994, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34592236

RESUMO

AIM OF THE STUDY: Breast cancer is caused by abnormal growth of the cells and progressed due to the over-expression of estrogen (ER) and progesterone (PR). The current study was designed to evaluate the anti-tumor activity of 2,4,6 tris-methyphenylamino1,3,5-triazine compound (MPAT) in N-nitroso, N-methyl urea (NMU)-induced mammary gland cancer. METHODS: Molecular docking and in-vitro studies were conducted before the in-vivo analysis. Female Albino rats were divided into 5 groups (n = 6). Group I received Carboxymethylcellulose (CMC) (1 mL/100 g). Group II (diseased group) received NMU 50 mg/kg. Group III (standard group) received tamoxifen (5 mg/kg). Group IV-V received MPAT at doses of 30 and 60 mg/kg respectively. All groups received NMU intraperitoneally except the control group at 3 weeks intervals for 12 weeks. After 12 weeks of NMU dosing, MPAT was given for 15 consecutive days. Biochemical, oxidative stress markers, hormonal profile, and inflammatory mediators were analyzed. KEY FINDINGS: MPAT showed significant interaction with the selected targets in docking studies. An over-expression of ER and PR was observed in NMU-treated rats which were restored significantly after MPAT administration. Nitrite and MDA levels were high in the diseased group and MPAT treatment attenuated the oxidative damage after treatment. Antioxidants such as superoxide dismutase (SOD), Catalase (CAT), total sulfhydryl (TSH), glutathione (GSH), and Lactate dehydrogenase (LDH) values were low in NMU-treated rats. SIGNIFICANCE: This study concluded that MPAT can be used as an anticancer agent due to its significant effects on down-regulating the hormonal profile and oxidative stress markers.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Estrogênios/metabolismo , Mediadores da Inflamação/antagonistas & inibidores , Progesterona/metabolismo , Triazinas/farmacologia , Animais , Antineoplásicos/química , Regulação para Baixo , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Células MCF-7 , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo , Progesterona/antagonistas & inibidores , Ratos , Tamoxifeno/farmacologia , Triazinas/química
4.
Commun Biol ; 4(1): 954, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376799

RESUMO

Longitudinal menstrual cycle studies allow to investigate the effects of ovarian hormones on brain organization. Here, we use spectral dynamic causal modelling (spDCM) in a triple network model to assess effective connectivity changes along the menstrual cycle within and between the default mode, salience and executive control networks (DMN, SN, and ECN). Sixty healthy young women were scanned three times along their menstrual cycle, during early follicular, pre-ovulatory and mid-luteal phase. Related to estradiol, right before ovulation the left insula recruits the ECN, while the right middle frontal gyrus decreases its connectivity to the precuneus and the DMN decouples into anterior/posterior parts. Related to progesterone during the mid-luteal phase, the insulae (SN) engage to each other, while decreasing their connectivity to parietal ECN, which in turn engages the posterior DMN. When including the most confident connections in a leave-one out cross-validation, we find an above-chance prediction of the left-out subjects' cycle phase. These findings corroborate the plasticity of the female brain in response to acute hormone fluctuations and may help to further understand the neuroendocrine interactions underlying cognitive changes along the menstrual cycle.


Assuntos
Estradiol/metabolismo , Ciclo Menstrual/fisiologia , Vias Neurais/fisiologia , Progesterona/metabolismo , Adulto , Mapeamento Encefálico , Feminino , Humanos , Adulto Jovem
6.
Sci Rep ; 11(1): 16287, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381107

RESUMO

Hyperandrogenic women with PCOS show disrupted decidualization (DE) and placentation. Dihydrotestosterone (DHT) is reported to enhance DE in non-PCOS endometrial stromal cells (eSCCtrl); however, this has not been assessed in PCOS cells (eSCPCOS). Therefore, we studied the transcriptome profile of non-decidualized (non-DE) and DE eSCs from women with PCOS and Ctrl in response to short-term estradiol (E2) and/or progesterone (P4) exposure with/without (±) DHT. The non-DE eSCs were subjected to E2 ± DHT treatment, whereas the DE (0.5 mM 8-Br-cAMP, 96 h) eSCs were post-treated with E2 and P4 ± DHT, and RNA-sequenced. Validation was performed by immunofluorescence and immunohistochemistry. The results showed that, regardless of treatment, the PCOS and Ctrl samples clustered separately. The comparison of DE vs. non-DE eSCPCOS without DHT revealed PCOS-specific differentially expressed genes (DEGs) involved in mitochondrial function and progesterone signaling. When further adding DHT, we detected altered responses for lysophosphatidic acid (LPA), inflammation, and androgen signaling. Overall, the results highlight an underlying defect in decidualized eSCPCOS, present with or without DHT exposure, and possibly linked to the altered pregnancy outcomes. We also report novel factors which elucidate the mechanisms of endometrial dysfunction in PCOS.


Assuntos
Androgênios/metabolismo , Endométrio/metabolismo , Síndrome do Ovário Policístico/metabolismo , Células Estromais/metabolismo , Adulto , Di-Hidrotestosterona/metabolismo , Estradiol/metabolismo , Feminino , Humanos , Gravidez , Progesterona/metabolismo , Transdução de Sinais/fisiologia
7.
PLoS One ; 16(8): e0255368, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34343192

RESUMO

Most of our knowledge on reproductive biology of gray whales dates back to scientific research conducted during commercial whaling in the late 1950s and 1960s. The goal of the present study was to provide updated insights on reproductive physiology of gray whales, using progesterone and testosterone as biomarkers. We measured hormone concentrations using enzyme immunoassay (EIA) techniques in blubber biopsies collected from 106 individual whales from March to November over a span of 12 years (2004-2016) between California and Alaska. We found testosterone concentrations in males to increase significantly with age (P = 0.03). Adult males showed significantly elevated testosterone concentrations when sampled in the fall compared to the summer (P = 0.01), likely indicating physiological preparation for mating. We measured testosterone concentrations in females of different age classes, but no statistical differences were found. We found significantly higher progesterone concentrations in pregnant females compared to non-pregnant females and adult males (P< 0.001), indicating progesterone is a valid biomarker for pregnancy in gray whales. Both female and male calves had elevated progesterone concentrations, suggesting maternal transfer via lactation. We fit a mixture of two normal distributions to progesterone data from all non-calf females to identify clusters of high and low progesterone and estimated the probability of being pregnant for whales of unknown reproductive status. With this approach we identified likely pregnant and non-pregnant animals. This study represents an important milestone on reproductive profiles in this population, that can be used to estimate more accurate and precise reproductive parameters to be used for better understanding population dynamics of gray whales.


Assuntos
Biomarcadores/metabolismo , Progesterona/metabolismo , Comportamento Sexual Animal/fisiologia , Testosterona/metabolismo , Baleias/fisiologia , Fatores Etários , Alaska , Animais , California , Feminino , Lactação/metabolismo , Masculino , Gravidez
8.
Front Immunol ; 12: 677870, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220823

RESUMO

Background: 16S sequencing results are often used for Machine Learning (ML) tasks. 16S gene sequences are represented as feature counts, which are associated with taxonomic representation. Raw feature counts may not be the optimal representation for ML. Methods: We checked multiple preprocessing steps and tested the optimal combination for 16S sequencing-based classification tasks. We computed the contribution of each step to the accuracy as measured by the Area Under Curve (AUC) of the classification. Results: We show that the log of the feature counts is much more informative than the relative counts. We further show that merging features associated with the same taxonomy at a given level, through a dimension reduction step for each group of bacteria improves the AUC. Finally, we show that z-scoring has a very limited effect on the results. Conclusions: The prepossessing of microbiome 16S data is crucial for optimal microbiome based Machine Learning. These preprocessing steps are integrated into the MIPMLP - Microbiome Preprocessing Machine Learning Pipeline, which is available as a stand-alone version at: https://github.com/louzounlab/microbiome/tree/master/Preprocess or as a service at http://mip-mlp.math.biu.ac.il/Home Both contain the code, and standard test sets.


Assuntos
Bactérias/classificação , Bactérias/genética , Colite/microbiologia , Microbioma Gastrointestinal/genética , Aprendizado de Máquina , Mucosite/microbiologia , Adulto , Animais , Colite/metabolismo , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Interleucina-1alfa/metabolismo , Camundongos , Mucosite/metabolismo , Redes Neurais de Computação , Filogenia , Gravidez , Progesterona/metabolismo , RNA Ribossômico 16S/genética
9.
Pol J Vet Sci ; 24(2): 183-190, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34250776

RESUMO

The aim of this study was to evaluate the possibility to predict outcomes of artificial insemi- nation (AI) in dairy cows based on in-line milk progesterone (P4) concentration. The research was carried out on the herd of loose housing 245 dairy cows of 2-4 lactations, with average milk yielding 11.000 kg per cow. Milk sampling, measuring, and recording of milk P4 concentration was carried out using the Herd Navigator (HN). The grouping was performed according to the following three indices: the first by reproductive condition - pregnant or not pregnant after AI, the second by P4 concentration from day 20 before AI to day 20 after AI, and the third by P4 concentration at AI time. There was a significant difference in P4 concentration in the group of pregnant cows from day 15 to day 9 before AI, and it was by 18.3% higher com- pared to that in the group of non-pregnant cows in the said period (p⟨0.01). The milk P4 concen- trations began to differ mostly from day 10 after AI. At that time, the average P4 concentration in the group of pregnant dairy cows was by 36.8% higher compared to that in the group of non-pregnant cows (p⟨0.01). A statistically significant difference between the ratio of the cows with high, medium, and low P4 concentration on days 20-16 before AI (p⟨0.01) was determined. The highest number of cows with up to 2-3 ng/ml P4 concentration became pregnant at the AI time. In-line milk P4 records captured on day 10-15 before AI can be used to predict the proper for reproduction period. By P4 concentrations on day10 after AI, the ratio of pregnant cows in herd can be assessed.


Assuntos
Bovinos , Inseminação Artificial/veterinária , Leite/química , Prenhez , Progesterona/química , Progesterona/metabolismo , Animais , Feminino , Masculino , Gravidez , Prenhez/fisiologia
10.
Sci Rep ; 11(1): 14839, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290309

RESUMO

Objective was to elucidate the effects of heat stress (HS) on embryo development during first 16 gestational days (GD) and circulating hormone concentrations on GD-16 in lactating Holstein cows. Cows in HS and control (CON) groups were exposed to temperature humidity index (THI) of ≥ 73 and < 73, respectively, for 3 weeks before the experiment. GD-7 (67 vs 49%) and GD-16 (52 vs. 31%) conception rates following single insemination were greater (P < 0.01) for CON compared with HS cows. Control cows produced more GD-7 transferrable embryos following superovulation compared with HS cows (84.8 vs 53.1%; P < 0.001). Mean (± SEM) length (45.2 ± 10.6 vs. 59.2 ± 9.1 mm) and weight (31.4 ± 4.3 vs. 42.4 ± 6.2 mg) of GD-16 conceptus were greater for CON compared with HS cows (P < 0.05). Control cows yielded more filamentous conceptus (≥ 25 mm) compared with HS cows (71 vs 45%; P < 0.05). Progesterone (2.09-fold) was higher, and cortisol (1.86-fold), prolactin (1.60-fold), substance-P (1.55-fold), Isoprostane-8 (1.34-fold) and prostaglandin F metabolites (1.97-fold) were lower in CON compared with HS cows (P < 0.05). Progesterone positively, and substance-P, isoprostane-8 and the THI negatively were associated with GD-16 conceptus length (P < 0.05). In conclusion, altered hormones concentrations in heat-stressed cows plausibly resulted in lower GD-7 and GD-16 conception rates, fewer GD-7 transferable embryos, and stunted GD-16 conceptus elongation.


Assuntos
Bovinos/embriologia , Bovinos/fisiologia , Desenvolvimento Embrionário/fisiologia , Resposta ao Choque Térmico/fisiologia , Gravidez/fisiologia , Animais , Bovinos/metabolismo , Feminino , Idade Gestacional , Hidrocortisona/metabolismo , Isoprostanos/metabolismo , Lactação , Progesterona/metabolismo , Prolactina/metabolismo , Prostaglandinas F/metabolismo , Substância P/metabolismo
11.
Ecotoxicol Environ Saf ; 220: 112389, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34082246

RESUMO

Triclosan (TCS) is an endocrine-disrupting chemical (EDC), which is used ubiquitously as an antimicrobial ingredient in healthcare products and causes contamination in the environment such as air, water, and biosolid-amended soil. Exposure to TCS may increase the risk of reproduction diseases and health issues. Several groups, including ours, have proved that TCS increased the biosynthesis of steroid hormones in different types of steroidogenic cells. However, the precise mechanism of toxic action of TCS on increased steroidogenesis at a molecular level remains to be elucidated. In this study, we try to address the mode of action that TCS affects energy metabolism with increased steroidogenesis. We evaluated the adverse effects of TCS on energy metabolism and steroidogenesis in human ovarian granulosa cells. The goal is to elucidate how increased steroidogenesis can occur with a shortage of adenosine triphosphate (ATP) whereas mitochondria-based energy metabolism is impaired. Our results demonstrated TCS increased estradiol and progesterone levels with upregulated steroidogenesis gene expression at concentrations ranging from 0 to 10 µM. Besides, glucose consumption, lactate level, and pyruvate kinase transcription were increased. Interestingly, the lactate level was attenuated with increased steroidogenesis, suggesting that pyruvate fate was shifted away from the formation of lactate towards steroidogenesis. Our study is gathering evidence suggesting a mode of action that TCS changes energy metabolism by predominating glucose flow towards the biosynthesis of steroid hormones. To the best of our knowledge, this is the first report that TCS presents such toxic action in disrupting hormone homeostasis.


Assuntos
Anti-Infecciosos/toxicidade , Disruptores Endócrinos/toxicidade , Células da Granulosa/efeitos dos fármacos , Triclosan/toxicidade , Anaerobiose , Animais , Estradiol/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células da Granulosa/metabolismo , Humanos , Progesterona/metabolismo
12.
Ecotoxicol Environ Saf ; 221: 112418, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34146982

RESUMO

BACKGROUND: Bisphenol A (BPA), a widely used plastic monomer and plasticizer, is detectable in blood, urine and semen of a healthy people, with concentrations ranging from 0.1 nM to 10 nM. It has been shown that in vitro exposure of BPA as low as 0.001 nM could significantly inhibited mouse sperm motility and acrosome reaction. However, it is still unclear whether BPA at those physiologically detectable concentration affects human sperm. METHODS: The effects of different concentrations of BPA (0, 10-3, 10-2, 10-1, 10, 103 nM) on sperm functions were examined, including human sperm viability, kinematic parameters, hyperactivation and capacitation. RESULTS: BPA caused a remarkable decline in human sperm viability, motility and progressive motility, hyperactivation, capacitation and progesterone-induced acrosome reaction. Mechanism studies showed that BPA could suppress the protein tyrosine phosphorylation level of human sperm, but had no effect on sperm calcium signaling. CONCLUSIONS: Physiologically detectable concentrations of BPA may impair human sperm functions via suppressing protein tyrosine phosphorylation of human sperm, implying that environmental pollution of BPA might be a factor contributing to male infertility.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Plastificantes/toxicidade , Espermatozoides/efeitos dos fármacos , Reação Acrossômica/efeitos dos fármacos , Humanos , Masculino , Fosforilação/efeitos dos fármacos , Progesterona/metabolismo , Proteínas/metabolismo , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/fisiologia , Tirosina/metabolismo
13.
Am J Physiol Endocrinol Metab ; 321(2): E281-E291, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34191631

RESUMO

Hypothalamic-pituitary-gonadal (HPG) axis suppression in exercising women can be caused by low energy availability (EA), but the impact of a real-world, multistressor training environment on reproductive and metabolic function is unknown. This study aimed to characterize reproductive and metabolic adaptation in women undertaking basic military training. A prospective cohort study in women undertaking 11-month initial military training (n = 47) was carried out. Dynamic low-dose 1-h gonadotrophin-releasing hormone (GnRH) tests were completed after 0 and 7 mo of training. Urine progesterone was sampled weekly throughout. Body composition (dual X-ray absorptiometry), fasting insulin resistance (homeostatic modeling assessment 2, HOMA2), leptin, sex steroids, anti-Müllerian hormone (AMH), and inhibin B were measured after 0, 7, and 11 mo with an additional assessment of body composition at 3 mo. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responses were suppressed after 7 mo (both P < 0.001). Among noncontraceptive users (n = 20), 65% had regular (23-35 days) cycles preenrollment, falling to 24% by 7 mo of training. Of women in whom urine progesterone was measured (n = 24), 87% of cycles showed no evidence of ovulation. There was little change in AMH, LH, and estradiol, although inhibin B and FSH increased (P < 0.05). Fat mass fluctuated during training but at month 11 was unchanged from baseline. Fat-free mass did not change. Visceral adiposity, HOMA2, and leptin increased (all P < 0.001). HPG axis suppression with anovulation occurred in response to training without evidence of low EA. Increased insulin resistance may have contributed to the observed pituitary and ovarian dysfunction. Our findings are likely to represent an adaptive response of reproductive function to the multistressor nature of military training.NEW & NOTEWORTHY We characterized reproductive endocrine adaptation to prolonged arduous multistressor training in women. We identified marked suppression of hypothalamic-pituitary-gonadal (HPG) axis function during training but found no evidence of low energy availability despite high energy requirements. Our findings suggest a complex interplay of psychological and environmental stressors with suppression of the HPG axis via activation of the hypothalamic-pituitary adrenal (HPA) axis. The neuroendocrine impact of nonexercise stressors on the HPG axis during arduous training should be considered.


Assuntos
Adaptação Fisiológica , Fenômenos Reprodutivos Fisiológicos , Estresse Psicológico/metabolismo , Adulto , Composição Corporal , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Progesterona/metabolismo , Estudos Prospectivos , Adulto Jovem
14.
Reprod Domest Anim ; 56(9): 1235-1242, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34173284

RESUMO

Ghrelin is a gut hormone related to energy balance and reproductive functions. The aim of this study was to evaluate the effect of ghrelin antagonist D-Lys3-GHRP-6 (GA) as a potential agent that prevents ghrelin effects during bovine oocyte maturation on progesterone production, cumulus cell (CC) viability, CC DNA damage and embryo development and hatching rates. Ghrelin's potential to induce oxidative stress in cumulus-oocyte complexes (COC) was also evaluated. COCs were cultured for 24 hr in medium without supplementation (C) or supplemented with 60 pM ghrelin (Ghrelin60), Ghrelin60 + 20 pM GA (GA20), Ghrelin60 + 60 pM GA (GA60) or Ghrelin60 + 100 pM GA (GA100) for experiment I. For experiment II, C and Ghrelin60 treatments were used. Differences between C and Ghrelin60 and the linear or quadratic association between GAs on Ghrelin60 were evaluated. Results demonstrated that Ghrelin60 increased progesterone concentration, reduced CC viability, induced CC DNA damage and decreased blastocyst and hatching rate compared with C (p < .05). GA20, GA60 and GA100 had a linear effect on CC genetic damage index (p ≤ .05) and a quadratic effect on CC viability (p < .01). GA20 counteracted the low hatching rate produced by Ghrelin60. However, GAs did not counteract progesterone concentration and blastocyst rate (p ≥ .21). GRH60 did not differ from C in the oxidative status (p ≥ .19). Our study highlights that GA could prevent the negative effects of ghrelin during bovine IVM.


Assuntos
Células do Cúmulo/efeitos dos fármacos , Técnicas de Maturação in Vitro de Oócitos/veterinária , Oligopeptídeos/farmacologia , Oócitos/efeitos dos fármacos , Animais , Blastocisto/efeitos dos fármacos , Bovinos , Dano ao DNA , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Grelina/farmacologia , Técnicas de Maturação in Vitro de Oócitos/métodos , Estresse Oxidativo , Progesterona/metabolismo
15.
Biochem Biophys Res Commun ; 559: 56-61, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-33932900

RESUMO

To elucidate the impact of glucocorticoids on ovarian steroidogenesis and its molecular mechanism by focusing on bone morphogenetic proteins (BMPs), we examined the effect of dexamethasone (Dex) on estradiol and progesterone synthesis by using primary culture of rat granulosa cells. It was revealed that Dex treatment dose-dependently decreased estradiol production but increased progesterone production induced by follicle-stimulating hormone (FSH) by granulosa cells. In accordance with the effects of Dex on estradiol synthesis, Dex suppressed P450arom mRNA expression and cAMP synthesis induced by FSH. Dex treatment in turn enhanced basal as well as FSH-induced levels of mRNAs encoding the enzymes for progesterone synthesis including P450scc and 3ßHSD but not StAR and 20αHSD. Of note, Dex treatment significantly upregulated transcription of the BMP target gene Id-1 and Smad1/5/9 phosphorylation in the presence of BMP-15 among the key ovarian BMP ligands. It was also found that Dex treatment increased the expression level of BMP type-I receptor ALK-6 among the type-I and -II receptors for BMP-15. Inhibitory Smad6/7 expression was not affected by Dex treatment. On the other hand, BMP-15 treatment upregulated glucocorticoid receptor (GR) expression in granulosa cells. Collectively, it was revealed that glucocorticoids elicit differential effects on ovarian steroidogenesis, in which GR and BMP-15 actions are mutually enhanced in granulosa cells.


Assuntos
Proteína Morfogenética Óssea 15/metabolismo , Dexametasona/farmacologia , Estradiol/metabolismo , Glucocorticoides/farmacologia , Ovário/efeitos dos fármacos , Progesterona/metabolismo , Animais , Células Cultivadas , Feminino , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Ovário/metabolismo , Ratos
16.
Sci Rep ; 11(1): 9666, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33958648

RESUMO

The steroid hormone progesterone accounts for immune tolerance in pregnancy. Enhanced progesterone metabolism to 6α-OH-pregnanolone occurs in complicated pregnancies such as in preeclampsia with preterm delivery or intrauterine growth restriction, and in cancer. As lymphatic endothelial cells (LECs) promote tumor immunity, we hypothesized that human LECs modify progesterone bioavailability. Primary human LECs and mice lymph nodes were incubated with progesterone and progesterone metabolism was analyzed by thin layer chromatography and liquid chromatography-mass spectrometry. Expression of steroidogenic enzymes, down-stream signal and steroid hormone receptors was assessed by Real-time PCR. The placental cell line HTR-8/SV neo was used as reference. The impact of the progesterone metabolites of interest was investigated on the immune system by fluorescence-activated cell sorting analysis. LECs metabolize progesterone to 6α-OH-pregnanolone and reactivate progesterone from a precursor. LECs highly express 17ß-hydroxysteroid dehydrogenase 2 and are therefore antiandrogenic and antiestrogenic. LECs express several steroid hormone receptors and PIBF1. Progesterone and its metabolites reduced TNF-α and IFN-γ production in CD4+ and CD8+ T cells. LECs modify progesterone bioavailability and are a target of steroid hormones. Given the global area represented by LECs, they might have a critical immunomodulatory control in pregnancy and cancer.


Assuntos
Células Endoteliais/metabolismo , Progesterona/metabolismo , Animais , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular , Cromatografia em Camada Delgada , Feminino , Citometria de Fluxo , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Interferon gama/metabolismo , Linfonodos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Placenta/citologia , Placenta/metabolismo , Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Fator de Necrose Tumoral alfa/metabolismo
17.
J Histochem Cytochem ; 69(6): 373-388, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33985378

RESUMO

Grainyhead-like 2 (Grhl2) is a transcription factor regulating cell adhesion genes. Grhl2 acts as an epithelial-mesenchymal transition suppressor, and it is a proto-oncogene involved in estrogen-stimulated breast cancer proliferation. However, its expression during ovarian hormone-dependent mammary ductal development remains obscure. We here examined Grhl2 expression in the mammary gland of normal and steroid-replaced ovariectomized mice. Grhl2 protein signals were detected in both the mammary luminal epithelial and myoepithelial nuclei. The ratio and density of Grhl2-positive nuclei increased after the onset of puberty and progressed with age, whereas Grhl2-negative epithelial cells were detected in mature ducts. Claudin 3, claudin 4, claudin 7, and E-cadherin gene expression in the mammary gland was upregulated, and their expression was highly correlated with Grhl2 gene expression. Furthermore, Grhl2 mRNA expression and ductal lumen width were significantly increased by the combined treatment of estrogen and progesterone compared with estrogen alone. These results suggest that Grhl2 expressed in the luminal epithelial and myoepithelial cells from the early phase of ductal development, controlling the expression of cell adhesion molecules to establish functional ducts.


Assuntos
Glândulas Mamárias Animais/crescimento & desenvolvimento , Fatores de Transcrição/genética , Animais , Estrogênios/metabolismo , Feminino , Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/ultraestrutura , Camundongos Endogâmicos C57BL , Progesterona/metabolismo , RNA Mensageiro/genética
18.
Eur J Pharmacol ; 903: 174134, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33940031

RESUMO

Ischemia-reperfusion (IR) injury is a major limitation of ovarian transplantation which threatens the follicular and graft survival. Taurine as a potent anti-oxidant, anti-apoptotic and anti-inflammatory agent, can prevent graft damages due to IR. We aimed to investigate the effect of taurine on the follicular survival and function of autotransplanted mouse ovaries. Female mice (4-5 weeks old) were divided into: control, autograft and autograft + taurine (200 mg/kg/day). The level of CD31 expression was evaluated two days (48 h) post transplantation. In addition, on day 7 post transplantation the serum levels of malondialdehyde (MDA) and the total antioxidant capacity (TAC) were assessed. Also, 28 days post transplantation; ovaries were studied stereologically and the percentage of apoptotic follicles, level of GDF9 expression and the serum concentrations of progesterone and estradiol were measured. Data were analyzed using one-way ANOVA and Tukey's test and the means were considered significantly different at P < 0.05. The total volume of the ovary (P < 0.01), volume of the cortex (P < 0.01) and medulla (P < 0.04), total number of different types of follicles, expression of GDF9 and CD31 and also the levels of progesterone, estradiol and TAC increased significantly in the autograft + taurine group compared to the autograft group (P < 0.001). The MDA level and apoptosis rate decreased significantly in the autograft + taurine group compared to the autograft group (P < 0.001). Taurine could significantly improve follicular survival and the function of grafted ovaries by accelerating the angiogenesis and reducing oxidative stress and apoptosis.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Fator 9 de Diferenciação de Crescimento/metabolismo , Folículo Ovariano/efeitos dos fármacos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Taurina/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Estradiol/metabolismo , Feminino , Malondialdeído/metabolismo , Camundongos , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Folículo Ovariano/transplante , Estresse Oxidativo/efeitos dos fármacos , Progesterona/metabolismo , Taurina/uso terapêutico , Transplante Autólogo
19.
Anim Reprod Sci ; 229: 106760, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33962315

RESUMO

Effects of nutrition on insulin-like growth factor-I (IGF-I), IGF binding proteins (IGFBP), and insulin in plasma and dominant follicles were evaluated at day 72 and 56 (Exp. 1, n = 12 and Exp. 2, n = 28, respectively) postpartum in anovulatory primiparous beef cows. Cows were stratified based on body condition score at calving and randomly assigned to nutritional treatments: maintain (M), 2.27 kg of a 40 % CP supplement per day and ad libitum hay; or gain (G), ad libitum access to a 50 % concentrate diet and ad libitum hay. Blood samples were collected twice weekly starting 30 days postpartum. Ovarian follicles were evaluated using ultrasonography commencing 42 (Exp. 1) or 30 (Exp. 2) days postpartum. Body weight and condition score were greater (P < 0.05) for cows of G than M groups and postpartum interval to luteal function was longer for cows of the M than G group. Insulin and IGF-I concentrations in follicular fluid (FF) and plasma were greater (P < 0.05) for cows of the G than M group at follicular aspiration. Plasma and FF IGFBP4 and IGFBP5 concentrations were greater (P <  0.05) in Exp. 2, and IGFBP5 was greater in Exp. 1 for cows of the G than M group. Treatment did not affect FF steroid concentrations or granulosal cell CYP19A1, PAPPA, IGFBP4, and IGFBP5 mRNA abundance. These results indicate concentrations of IGF-I, insulin, IGFBP4, and IGFBP5 in FF and plasma are affected by nutritional intake and may be related to follicular function.


Assuntos
Bovinos/fisiologia , Dieta/veterinária , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Folículo Ovariano/efeitos dos fármacos , Período Pós-Parto , Somatomedinas/metabolismo , Androstenodiona/química , Androstenodiona/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Composição Corporal , Peso Corporal , Bovinos/sangue , Estradiol/química , Estradiol/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Folículo Ovariano/metabolismo , Progesterona/química , Progesterona/metabolismo , Somatomedinas/genética
20.
Mol Med Rep ; 23(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33899118

RESUMO

Glioblastomas (GBMs) are the most frequent and malignant type of brain tumor. It has been reported that progesterone (P4) regulates the progression of GBMs by modifying the expression of genes that promote cell proliferation, migration and invasion; however, it is not fully understood how these processes are regulated. It is possible that P4 mediates some of these effects through changes in the microRNA (miRNA) expression profile in GBM cells. The present study investigated the effects of P4 on miRNAs expression profile in U­251MG cells derived from a human GBM. U­251MG cells were treated for 6 h with P4, RU486 (an antagonist of the intracellular progesterone receptor), the combined treatment (P4+RU486) and cyclodextrin (vehicle) and then a miRNA microarray analysis conducted. The expression analysis revealed a set of 190 miRNAs with differential expression in the treatments of P4, RU486 and P4+RU486 in respect to the vehicle and P4 in respect to P4+RU486, of which only 16 were exclusively regulated by P4. The possible mRNA targets of the miRNAs regulated by P4 could participate in the regulation of proliferation, cell cycle progression and cell migration of GBMs. The present study provided insight for understanding epigenetic modifications regulated by sex hormones involved in GBM progression, and for identifying potential therapeutic strategies for these brain tumors.


Assuntos
Glioblastoma/genética , MicroRNAs/genética , Progesterona/metabolismo , Linhagem Celular Tumoral , Glioblastoma/metabolismo , Humanos , MicroRNAs/metabolismo , Mifepristona/farmacologia , Receptores de Progesterona/antagonistas & inibidores , Transcriptoma/efeitos dos fármacos
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