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1.
Chem Biol Interact ; 324: 109093, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32298659

RESUMO

Polycystic Ovary Syndrome (PCOS), as a common endocrine disorder is accompanied by hyperandrogenism, insulin resistance, ovulation problems, and infertility. Various types of off-label drugs like metformin have been used for the management of targeted problems caused by PCOS such as insulin resistance and hyperandrogenism. Nicotinamide (NAM) acts as a substrate of visfatin and Nicotinamide N-Methyltransferase (NNMT) leading to the generation of Nicotinamide Adenine Dinucleotide (NAD) and N1-Methylnicotinamide (MNAM), respectively. MNAM is known as an anti-inflammatory, anti-thrombosis, and anti-diabetic agent. In this study, the effects of NAM and MNAM on metabolic and endocrine abnormalities were evaluated in the adipose and ovarian tissues of a letrozole-induced rat model of PCOS. Our results showed that MNAM and NAM reversed abnormal estrous cycle and reduced the serum testosterone levels and CYP17A1 gene expression. Furthermore, all therapeutic factors improved HOMA-IR after treatment and NAM significantly increased the expression of GLUT4 and decreased the gene expression of visfatin. Also, MNAM diminished the gene expression of visfatin and resistin. It is noteworthy that all the therapeutic factors successfully activated the AMPK. In summary, this study is the first study reported beneficial effects of NAM and MNAM on the treatment of PCOS. Additionally, the alleviative effects of our therapeutic factors may be partially mediated by the AMPK-dependent manner due to the contribution of the AMPK in the expression of CYP17A1, visfatin, resistin, and GLUT4. Although more studies are required to unravel the exact mode of actions of MNAM and NAM in the PCOS, the findings of the current study shed light on an urgent need for discovering novel therapeutic pharmaceuticals regarding the treatment of PCOS.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Ovário/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Citocinas/genética , Citocinas/metabolismo , Ciclo Estral/efeitos dos fármacos , Feminino , Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Hiperandrogenismo/tratamento farmacológico , Hormônio Luteinizante/metabolismo , Metformina/uso terapêutico , Nicotinamida Fosforribosiltransferase/genética , Nicotinamida Fosforribosiltransferase/metabolismo , Ratos Wistar , Resistina/genética , Resistina/metabolismo , Esteroide 17-alfa-Hidroxilase/genética , Esteroide 17-alfa-Hidroxilase/metabolismo , Testosterona/metabolismo
2.
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
3.
Anim Reprod Sci ; 210: 106200, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31635772

RESUMO

This aim of this study was to investigate the effectiveness of intravaginal devices (IVDs), containing medroxyprogesterone acetate (MPA), for controlling the estrous cycle in pubertal gilts. Gilts were assigned to four treatments: Control (no IVD); IVD containing 100 (IVD100), 200 (IVD200) or 400 mg (IVD400) of MPA. The IVDs were inserted on day 12 of the estrous cycle and maintained intra-vaginally for 14 days. The percentage of gilts in estrus, interval between IVD removal and estrous onset, adjusted farrowing rate (AFR), total number of piglets born (TPB), follicle size and serum progesterone (P4) were recorded. None of the gilts expressed estrus during the IVD treatment period. All gilts of the control group expressed estrus (15/15; 100%) which was greater (P =  0.03) than all IVD-treated gilts (33/44; 75%); however, there were no treatment differences (P =  0.09). The interval between IVD removal and estrous onset was shorter for IVD100 (3.8 ± 0.6 d) compared to IVD400 (5.3 ± 0.6 d; P = 0.05). The IVD400-treated gilts had smaller follicles than the IVD100-treated gilts (P =  0.05). The P4 concentrations were similar among treated groups (P =  0.99). The AFR did not differ among treatment groups (P = 0.37); however, the control group had a greater TPB than the other treatment groups (P =  0.04). The gilts treated with IVDs had longer interval to estrous expression. The most effective dosage was 400 mg of MPA, considering both the minimal follicular growth during the IVD treatment period and the lesser numbers of persistent follicles.


Assuntos
Ciclo Estral/efeitos dos fármacos , Acetato de Medroxiprogesterona/farmacologia , Suínos/fisiologia , Administração Intravaginal , Animais , Estro/fisiologia , Feminino , Acetato de Medroxiprogesterona/administração & dosagem , Folículo Ovariano/efeitos dos fármacos
4.
PLoS One ; 14(9): e0223274, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31568518

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-aged women that is comprised of two out of the following three features: hyperandrogenism, oligo- or amenorrhea, or polycystic ovaries. In addition to infertility, many women with PCOS have metabolic dysregulation that increases the risk of developing type 2 diabetes, hypertension, and non-alcoholic fatty liver disease. Changes in the gut microbiome are associated with PCOS and gut microbes may be involved in the pathology of this disorder. Since PCOS often manifests in the early reproductive years, puberty is considered to be a critical time period for the development of PCOS. Exposure to sex steroid hormones during development results in permanent, organizational effects, while activational effects are transient and require the continued presence of the hormone. Androgens exert organizational effects during prenatal or early post-natal development, but it is unclear whether androgen excess results in organizational or activational effects during puberty. We recently developed a letrozole-induced PCOS mouse model that recapitulates both reproductive and metabolic phenotypes of PCOS. In this study, we investigated whether letrozole treatment of pubertal female mice exerts organizational or activational effects on host physiology and the gut microbiome. Two months after letrozole removal, we observed recovery of reproductive and metabolic parameters, as well as diversity and composition of the gut microbiome, indicating that letrozole treatment of female mice during puberty resulted in predominantly activational effects. These results suggest that if exposure to excess androgens during puberty leads to the development of PCOS, reduction of androgen levels during this time may improve reproductive and metabolic phenotypes in women with PCOS. These results also imply that continuous letrozole exposure is required to model PCOS in pubertal female mice since letrozole exerts activational rather than organizational effects during puberty.


Assuntos
Inibidores da Aromatase/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Hiperandrogenismo/tratamento farmacológico , Letrozol/farmacologia , Síndrome do Ovário Policístico/tratamento farmacológico , Reprodução/fisiologia , Adulto , Fatores Etários , Androgênios/biossíntese , Animais , Técnicas de Tipagem Bacteriana , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Preparações de Ação Retardada/administração & dosagem , Modelos Animais de Doenças , Ciclo Estral/efeitos dos fármacos , Feminino , Humanos , Hiperandrogenismo/genética , Hiperandrogenismo/metabolismo , Hiperandrogenismo/patologia , Insulina/sangue , Hormônio Luteinizante/sangue , Camundongos , Camundongos Endogâmicos C57BL , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Maturidade Sexual/fisiologia , Testosterona/sangue
5.
Anim Reprod Sci ; 209: 106172, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31514929

RESUMO

This study was conducted to evaluate effects of two administrations of d-cloprostenol at different intervals to synchronize the time of estrus and ovulation among estrous cyclic goats. In Experiment 1, 32 does were treated with 30 µg d-cloprostenol at 7.5 (T7.5, n = 16) or 11.5-day (T11.5, n = 16) intervals. In Experiment 2, the same treatments were administered and there was AI of the does (T7.5, n = 40 and T11.5, n = 38). In Experiment 1, ultrasonic assessments of ovaries were conducted at the time of the second administration of d-cloprostenol, every 12 h until detection of ovulation, and 7 days after estrous onset to detect the corpora lutea, as well as for pregnancy diagnosis 40 days after AI. In Experiment 1, the estrous response (90.6%, 29/32) was similar (P > 0.05) in both groups. Diameter of the largest follicle at the time of administration of the second dose was larger (P = 0.01) in the T7.5 than T11.5 group (7.0 compared with 5.7 mm), while the values for ovarian variables were similar (P > 0.05). In Experiment 2, the greatest (P < 0.001) synchrony in timing of initiation of estrus in does (T7.5 = 83.3% and T11.5 = 50.0%) occurred after the second day (36-48 h). The pregnancy rate tended (P = 0.0836) to be greater for does in the T7.5 (71.4%, 40/56) than T11.5 (55.6%, 30/54) group. With use of both protocols, there were acceptable estrous synchronization and pregnancy rates in estrous cyclic dairy goats.


Assuntos
Cloprostenol/administração & dosagem , Sincronização do Estro/métodos , Cabras , Inseminação Artificial , Taxa de Gravidez , Prenhez , Animais , Indústria de Laticínios , Esquema de Medicação/veterinária , Ciclo Estral/efeitos dos fármacos , Feminino , Inseminação Artificial/métodos , Inseminação Artificial/veterinária , Masculino , Ovulação/efeitos dos fármacos , Gravidez , Prenhez/efeitos dos fármacos , Fatores de Tempo
6.
Anim Reprod Sci ; 209: 106142, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31514932

RESUMO

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


Assuntos
Técnicas de Ablação , Anovulação/cirurgia , Líquido Folicular/metabolismo , Cavalos , Hormônio Luteinizante/sangue , Luteólise/efeitos dos fármacos , Folículo Ovariano/cirurgia , Técnicas de Ablação/métodos , Técnicas de Ablação/veterinária , Animais , Anovulação/complicações , Anovulação/metabolismo , Anovulação/veterinária , Gonadotropina Coriônica/farmacologia , Estudos Cross-Over , Dinoprosta/farmacologia , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/metabolismo , Feminino , Líquido Folicular/química , Líquido Folicular/efeitos dos fármacos , Hemorragia/complicações , Hemorragia/cirurgia , Hemorragia/veterinária , Doenças dos Cavalos/metabolismo , Doenças dos Cavalos/cirurgia , Folículo Ovariano/diagnóstico por imagem , Folículo Ovariano/patologia , Ovulação/efeitos dos fármacos , Indução da Ovulação/métodos , Indução da Ovulação/veterinária , Punções/métodos , Punções/veterinária , Ultrassonografia de Intervenção/métodos , Ultrassonografia de Intervenção/veterinária
7.
Int J Mol Sci ; 20(18)2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31533319

RESUMO

Induced by a bacterial infection, an immune/inflammatory challenge is a potent negative regulator of the reproduction process in females. The reduction of the synthesis of pro-inflammatory cytokine is considered as an effective strategy in the treatment of inflammatory induced neuroendocrine disorders. Therefore, the effect of direct administration of acetylcholinesterase inhibitor-neostigmine-into the third ventricle of the brain on the gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretions under basal and immune stress conditions was evaluated in this study. In the study, 24 adult, 2-years-old Blackhead ewes during the follicular phase of their estrous cycle were used. Immune stress was induced by the intravenous injection of LPS Escherichia coli in a dose of 400 ng/kg. Animals received an intracerebroventricular injection of neostigmine (1 mg/animal) 0.5 h before LPS/saline treatment. It was shown that central administration of neostigmine might prevent the inflammatory-dependent decrease of GnRH/LH secretion in ewes and it had a stimulatory effect on LH release. This central action of neostigmine is connected with its inhibitory action on local pro-inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)α synthesis in the hypothalamus, which indicates the importance of this mediator in the inhibition of GnRH secretion during acute inflammation.


Assuntos
Inibidores da Colinesterase/administração & dosagem , Endotoxinas/efeitos adversos , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/metabolismo , Hormônio Liberador de Gonadotropina/biossíntese , Hormônio Luteinizante/biossíntese , Neostigmina/administração & dosagem , Fase Folicular/efeitos dos fármacos , Fase Folicular/metabolismo , Hidrocortisona/biossíntese , Hipotálamo/metabolismo , Lipopolissacarídeos/efeitos adversos , Receptor Nicotínico de Acetilcolina alfa7/metabolismo
8.
Am J Physiol Regul Integr Comp Physiol ; 317(6): R903-R911, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31553663

RESUMO

Sex differences are evident in the presentation of metabolic symptoms. A shift of sex hormones that signal the onset of puberty combined with a poor diet consumed in adolescence is likely to have sex-specific, long-term impacts on adult physiology. Here, we expanded on existing literature to elucidate the sex-specific mechanisms driving physiological deficits following high fructose consumption. Male and female Wistar rats were fed a high-fructose (55%) diet beginning immediately postweaning for 10 wk. Female rats fed the high-fructose diet displayed elevated weight gain and extensive liver pathology consistent with markers of nonalcoholic fatty liver disease (NAFLD). Male rats fed the high-fructose diet exhibited increased circulating glucose along with moderate hepatic steatosis. Levels of cytokines and gene expression of inflammatory targets were not altered by fructose consumption in either sex. However, circulating levels of markers for liver health, including alanine transaminase and uric acid, and markers for epithelial cell death were altered by fructose consumption. From the alterations in these markers for liver health, along with elevated circulating triglycerides, it was evident that liver health had deteriorated significantly and that a number of factors were at play. Both adult fructose-fed male and female rats displayed motor deficits that correlated with aberrant structural changes at the neuromuscular junction; however, these deficits were exacerbated in males. These data indicate that consumption of a high-fructose diet beginning in adolescence leads to adult pathology that is modified by sex. Identification of these sex-specific changes has implications for treatment of clinical presentation of metabolic syndrome and related disorders.


Assuntos
Frutose/administração & dosagem , Fígado/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Ração Animal/análise , Animais , Glicemia , Doença Hepática Induzida por Substâncias e Drogas , Citocinas/genética , Citocinas/metabolismo , Dieta/veterinária , Ciclo Estral/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Gravidez , Ratos , Caracteres Sexuais
9.
Endocrinology ; 160(11): 2558-2572, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31503316

RESUMO

Exposure to bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical (EDC), is known to produce variable effects on female puberty and ovulation. This variability of effects is possibly due to differences in dose and period of exposure. Little is known about the effects of adult exposure to environmentally relevant doses of this EDC and the differences in effect after neonatal exposure. This study sought to compare the effects of neonatal vs adult exposure to a very low dose or a high dose of BPA for 2 weeks on ovulation and folliculogenesis and to explore the hypothalamic mechanisms involved in such disruption by BPA. One-day-old and 90-day-old female rats received daily subcutaneous injections of corn oil (vehicle) or BPA (25 ng/kg/d or 5 mg/kg/d) for 15 days. Neonatal exposure to both BPA doses significantly disrupted the estrous cycle and induced a decrease in primordial follicles. Effects on estrous cyclicity and folliculogenesis persisted into adulthood, consistent with a disruption of organizational mechanisms. During adult exposure, both doses caused a reversible decrease in antral follicles and corpora lutea. A reversible disruption of the estrous cycle associated with a delay and a decrease in the amplitude of the LH surge was also observed. Alterations of the hypothalamic expression of the clock gene Per1 and the reproductive peptide phoenixin indicated a disruption of the hypothalamic control of the preovulatory LH surge by BPA.


Assuntos
Compostos Benzidrílicos/toxicidade , Estrogênios não Esteroides/toxicidade , Ciclo Estral/efeitos dos fármacos , Ovário/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Fenóis/toxicidade , Fatores Etários , Animais , Animais Recém-Nascidos , Compostos Benzidrílicos/administração & dosagem , Estrogênios não Esteroides/administração & dosagem , Feminino , Fenóis/administração & dosagem , Ratos Wistar
10.
J Ethnopharmacol ; 245: 112183, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31445134

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hydrocotyle umbellata var.bonariensis Lam. (Hb), popularly known in Brazil as acariçoba and outside Brazil Hb by a number of names including marsh-pennywort, and many-flower, has traditionally been used in Ayurvedic medicine in the retardation of aging (Rasayana effect). AIM OF THE STUDY: The present study evaluated the effect of Hb treatment before and during paradoxical sleep deprivation (PSD) and sleep restriction (SR) on learning, memory, and acetylcholinesterase (AChE) brain activity. MATERIAL AND METHODS: Adult Swiss nulliparous female mice were randomly distributed among the experimental groups. The treated groups received the aqueous solution of Hb leaves orally at concentrations of 500 and 1.000 mg/kg. PSD and SR were induced by the multiple platform method, in which the animals remained for 3-days in PSD or 15-days in SR for 22 h per day. The collection of the vaginal epithelium occurred daily to determine the estrous cycle. Body mass gain was determined. The animals were submitted to the passive avoidance test and were then euthanized for the collection of brain tissue and the determination of cerebral cholinesterase activity. RESULTS: The aqueous solution of Hb was associated with a significant reduction in cholinesterase activity at both doses in the SR model, and at the dose of 1.000 mg/kg in the PSD model. Regarding the learning and memory test, the PSD group treated with 1.000 mg/kg presented significant improvement, whereas in the SR experiment none of the treated-groups showed any improvement in learning and memory. In the analysis of SR/PSD interference and/or Hb treatment on the estrous cycle, it was possible to observe that the treatment acted as a protector in the SR group, maintaining a normal cycle. CONCLUSIONS: The analyses showed that Hb was safe to use during periods of SR or PSD, acting as an adaptogen for these situations, in addition to being able to reduce cholinesterase activity, which suggests its neuroprotective action. In relation to the estrous cycle, Hb can act as a protector in SR situations.


Assuntos
Araliaceae , Aprendizagem/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/uso terapêutico , Privação do Sono/tratamento farmacológico , Acetilcolinesterase/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ciclo Estral/efeitos dos fármacos , Feminino , Camundongos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta , Privação do Sono/metabolismo , Privação do Sono/fisiopatologia
11.
Reprod Biol ; 19(3): 230-236, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31399370

RESUMO

Saccharine sodium and rebaudioside A are low-calorie sweeteners, and the biologic effects of these sweeteners in rat ovaries are related to the activity of sweet taste receptors. Data on the impact and regulatory mechanisms underlying such sweeteners on the reproduction of aged animals are currently lacking. In the present study we assessed how the consumption of sweeteners affects the ovarian cycle, ovulation, biochemical indices, and other biologic functions. Thirty-six 1-year-old mice were randomly divided into 3 groups: a control (C) group receiving regular water, a saccharin sodium group receiving a 7.5 mM solution, and the rebaudioside A group receiving a 2.5 mM solution for 30 days. We observed no significant changes in body weights in any group. However, uterine weight in the rebaudioside A group significantly increased in diestrus, and we recorded a significant increase in the percentage of abnormal estrous cycles and the number of corpora lutea in the treatment groups. TUNEL staining and Immunoreactivity for the apoptosis-inducing factor (AIF) confirmed apoptosis in granulosa cells, oocyte, and corpus luteum. Serum glucose increased significantly in both treatment groups and there was a significant increase in cholesterol in the rebaudioside A group. Furthermore, the saccharin sodium-treated group exhibited elevated serum progesterone levels compared with the other groups. In conclusion, sweeteners manifested deleterious effects on reproductive indices in aged mice.


Assuntos
Envelhecimento/fisiologia , Diterpenos de Caurano/farmacologia , Ovário/efeitos dos fármacos , Receptores Acoplados a Proteínas-G/agonistas , Sacarina/farmacologia , Animais , Diterpenos de Caurano/administração & dosagem , Ciclo Estral/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Progesterona/sangue , Distribuição Aleatória , Sacarina/administração & dosagem
12.
J Reprod Dev ; 65(5): 451-457, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31406064

RESUMO

This study aimed at investigating the efficacy of two protocols of estrous synchronization on follicular changes and hemodynamics. Pluriparous Egyptian buffaloes (n = 36) were synchronized either with controlled internal drug release (CIDR)-PGF2α (7-days CIDR insert with PGF2α injected on the 6th day; n = 18) or Ovsynch-CIDR (Ovsynch protocol concurrent with 7-days CIDR insert; n = 18). Blood sampling and ovarian ultrasound examinations (Grayscale, color and power Doppler modes) were conducted on the Day of CIDR removal, estrus, and luteal phase. Mean follicle diameter (MFD), first (1st-LF) and second (2nd-LF) largest follicle diameters, and E2 levels significantly increased in the CIDR-PGF2α group at CIDR withdrawal. Ovsynch-CIDR markedly fortified higher follicle population, MFD, and 1st-LF diameter at estrus and corpus luteum (CL) volume at the luteal phase in concomitant with increases (P < 0.05) in E2 (at estrus) and P4 (at luteal phase). At CIDR removal, the blue pixels in the dominant follicle (DF) were higher (1.5 times; P = 0.054) in the Ovsynch-CIDR than in the CIDR-PGF2α. At estrus, total blood flow (TBF) and power Doppler pixels (PDP) to DF(s) were noticeably higher (seven and 1.6 times; respectively) in the Ovsynch-CIDR than in CIDR-PGF2α (5906 ± 237 vs. 830 ± 60 pixels, P < 0.01 and 5479 ± 322 vs. 3377 ± 19 pixels, P < 0.05; respectively). At the luteal phase, TBF and PDP to the CL increased in the Ovsynch-CIDR group than in the CIDR-PGF2α group (11060 ± 965 vs. 7963 ± 480 pixels, 1.4 times, P = 0.05 and 18900 ± 1350 vs. 13220 ± 568 pixels, 1.1 times, P = 0.005; respectively). In conclusion, based on the improvement in synchronized follicular activity and hemodynamics, the Ovsynch-CIDR regimen is persuaded in Egyptian buffaloes.


Assuntos
Dinoprosta/administração & dosagem , Sincronização do Estro/métodos , Inseminação Artificial/veterinária , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/fisiologia , Animais , Cruzamento , Búfalos , Ciclo Estral/efeitos dos fármacos , Estro/efeitos dos fármacos , Feminino , Hemodinâmica , Fase Luteal/efeitos dos fármacos , Folículo Ovariano/diagnóstico por imagem , Esteroides/sangue , Ultrassonografia Doppler
13.
Theriogenology ; 138: 24-30, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31280182

RESUMO

Non-steroidal anti-inflammatory drugs (NSAIDs) are a therapeutic option for the treatment of inflammation. However, negative effects of non-selective NSAIDs for treatment of mares with endometritis have been described, including delayed uterine clearance and impairment of ovulations. Firocoxib is a specific cyclooxygenase-2 (COX-2) inhibitor and has the ability to act in the uterus of mares. We investigated the effects of firocoxib on ovulation rate, numbers of polymorphonuclear neutrophils (PMNs), and COX-2 protein levels in the endometrial tissue of susceptible mares after insemination. Two experiments were conducted. In experiment 1, twenty mares were evaluated in two consecutive estrous cycles broken into the following groups: Control - no pharmacological interference; Treatment - mares were treated with 0.2 mg/kg of firocoxib orally. The treatment began on the day of ovulation induction, and firocoxib was administered until one day after artificial insemination (AI). Ovulation was induced with 1 mg of deslorelin acetate and the mares were inseminated 24 h after the injection. Ovulation was confirmed 48 h after induction, and embryos were collected eight days after ovulation. Experiment 2: Nine mares susceptible to persistent mating-induced endometritis (PMIE) were artificially inseminated. The mares were examined with ultrasound and inseminated with fresh semen in two consecutive cycles, control and treated, in a cross-over study design. The amount of intrauterine fluid was measured, and endometrial samples were collected 24 h after AI. The number of PMNs was determined by endometrial cytology and biopsy, and COX-2 labeling in endometrial samples was evaluated by immunohistochemistry. Firocoxib treatment did not induce ovulatory failure or affect embryo recovery rate in Experiment 1. In Experiment 2, firocoxib treatment reduced inflammation after AI in mares as evidenced with results regarding PMN numbers/percentage and endometrial COX-2 staining. In conclusion, the proposed treatment with firocoxib reduced endometrial inflammation in mares susceptible to PMIE after breeding, with no adverse effects.


Assuntos
4-Butirolactona/análogos & derivados , Anti-Inflamatórios não Esteroides/administração & dosagem , Endometrite/tratamento farmacológico , Doenças dos Cavalos/tratamento farmacológico , Inflamação/prevenção & controle , Ovulação/efeitos dos fármacos , Sulfonas/administração & dosagem , 4-Butirolactona/administração & dosagem , Animais , Cruzamento , Estudos Cross-Over , Esquema de Medicação , Endometrite/veterinária , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/fisiologia , Feminino , Cavalos , Inflamação/etiologia , Inflamação/veterinária , Inseminação Artificial/efeitos adversos , Inseminação Artificial/veterinária , Masculino , Gravidez , Taxa de Gravidez , Resultado do Tratamento
14.
Behav Neurosci ; 133(5): 517-526, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31246079

RESUMO

Prior studies suggest that levels of ovarian hormones may affect learning and memory in rats, including studies of fear conditioning and extinction. We previously showed that female rats show reduced retention of extinction compared to males when measuring fear-potentiated startle, but not when measuring freezing behavior. One commonly reported observation in studies of freezing behavior is that rats with increased levels of estradiol during extinction learning show better retention of extinction than rats given extinction training when levels of estradiol are low. Here, we tested the hypothesis that fear extinction retention in a fear-potentiated startle paradigm in females is influenced by levels gonadal hormones, which we had not accounted for in our original report. We used the fear-potentiated startle paradigm to test if extinction learning was affected by estrous phase, ovariectomy, or acute systemic injections of estradiol in ovariectomized rats. We report that neither the expression nor extinction of fear-potentiated startle differed in rats given extinction training in proestrus compared to those in metestrus. Removal of the ovaries had no effect on fear acquisition or extinction learning as assessed by fear-potentiated startle. Finally, systemic injections of estradiol given to ovariectomized rats before extinction training had no effect on the expression of fear or the retention of extinction. Our findings suggest that the effect of female gonadal hormones on fear conditioning and extinction may depend on the measure of fear employed or by the parameters used to study fear learning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Extinção Psicológica/efeitos dos fármacos , Medo/efeitos dos fármacos , Hormônios Gonadais/fisiologia , Animais , Estradiol/farmacologia , Estrogênios/farmacologia , Ciclo Estral/efeitos dos fármacos , Extinção Psicológica/fisiologia , Medo/fisiologia , Feminino , Hormônios Gonadais/metabolismo , Ovariectomia , Ratos , Ratos Sprague-Dawley , Reflexo de Sobressalto/fisiologia
15.
Cell Mol Neurobiol ; 39(8): 1139-1149, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31250245

RESUMO

We examined the role of the estrogen receptors alpha (ERα) and beta (ERß) in of the preoptic-anterior hypothalamic area (POA-AHA) in the regulation of ovulation in rats. The number of ERα- and ERß-immunoreactive (-ir) cells was determined at 09:00, 13:00, and 17:00 h of each stage of the estrous cycle in intact rats. Additionally, the effects of blocking ERα and ERß on ovulation rate at 09:00 h on diestrus-2 or proestrus day through the microinjection of methyl-piperidino-pyrazole (MPP) or cyclofenil in either side of POA-AHA were evaluated. The number of ERα-ir and ERß-ir cells in POA-AHA varied in each phase of estrous cycle. Either MPP or cyclofenil in the right side of POA-AHA on diestrus-2 day reduced the ovulation rate, while at proestrus day it was decreased in rats treated in either side with MPP, and in those treated with cyclofenil in the left side. MPP or cyclofenil produced a decrease in the surge of luteinizing hormone levels (LH) and an increase in progesterone and follicle stimulating hormone (FSH). Replacement with synthetic luteinizing hormone-releasing hormone in non-ovulating rats treated with MPP or cyclofenil restored ovulation. These results suggest that activation of estrogen receptors on the morning of diestrus-2 and proestrus day asymmetrically regulates ovulation and appropriately regulates the secretion of FSH and progesterone in the morning and afternoon of proestrus day. This ensures that both, the preovulatory secretion of LH and ovulation, occur at the right time.


Assuntos
Núcleo Hipotalâmico Anterior/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Ovulação , Área Pré-Óptica/metabolismo , Animais , Núcleo Hipotalâmico Anterior/efeitos dos fármacos , Estradiol/sangue , Receptor alfa de Estrogênio/antagonistas & inibidores , Receptor beta de Estrogênio/antagonistas & inibidores , Ciclo Estral/efeitos dos fármacos , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ovulação/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Óvulo/metabolismo , Área Pré-Óptica/efeitos dos fármacos , Progesterona/sangue , Ratos
16.
Environ Toxicol ; 34(10): 1105-1113, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31240815

RESUMO

The aim of the present study was to evaluate the effects of maternal exposure to triclosan (TCS) during pregnancy and lactation on the uterine morphology of rat offspring. For this, 32 Wistar rat dams were distributed into four dose groups (eight mothers per group), and gavage daily, throughout pregnancy and lactation, as follows: Group I-control (GI): corn oil; Group II (GII): TCS diluted in corn oil at a dose of 75 mg/kg/d; Group III (GIII): TCS diluted in corn oil at a dose of 150 mg/kg/d; Group IV (GIV): TCS diluted in corn oil at a dose of 300 mg/kg/d. A female pup of each mother was selected, and at 90 days the pups were euthanized for weighing and collection of the uterus for histomorphometric analysis. The results showed that the mean litter weight was minor in all the groups treated with TCS, when compared with control. The levels thyroid hormones thyroxine (T4) and triiodothyronine (T3) in TCS mother rats were reduced; however the levels of thyroid stimulating hormone (TSH) were increases. The offspring of all groups exposed to TCS presented deregulation of the estrous cycle, compared with control. Analysis of the uterine histological structure demonstrated that all layers of the uterus were affected by the administration of TCS, and the morphometric analysis showed increased uterine layers thickness in the treated groups. We concluded that maternal exposure to TCS during pregnancy and lactation causes intrauterine development restriction, deregulation of the oestrous cycle, and alters uterine tissue in rat offspring.


Assuntos
Anti-Infecciosos Locais/efeitos adversos , Retardo do Crescimento Fetal/etiologia , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Triclosan/efeitos adversos , Útero/crescimento & desenvolvimento , Animais , Ciclo Estral/efeitos dos fármacos , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Retardo do Crescimento Fetal/fisiopatologia , Humanos , Lactação/efeitos dos fármacos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Ratos , Ratos Wistar , Hormônios Tireóideos/metabolismo , Útero/efeitos dos fármacos , Útero/fisiologia
17.
J Agric Food Chem ; 67(25): 7073-7081, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31240927

RESUMO

Obesity has been demonstrated as a disruptor of female fertility. Our previous study showed the antiobesity effects of calcium on HFD-fed male mice. However, the role of calcium in alleviating reproductive dysfunction of HFD-fed female mice remains unclear. Here, we found that HFD led to estrus cycle irregularity (longer cycle duration and shorter estrus period) and subfertility (longer conception time, lower fertility index, and less implantations) in mice. However, the HFD-induced reproductive abnormality was alleviated by calcium supplementation. Additionally, calcium supplementation enhanced activation/thermogenesis of BAT and browning of WAT in HFD-fed mice. Consequently, the abnormality of energy metabolism and glucose homeostasis induced by HFD were improved by calcium supplementation, with elevated metabolic rates and core temperature. In conclusion, these data showed that calcium supplementation alleviated HFD-induced estrous cycle irregularity and subfertility associated with concomitantly enhanced BAT thermogenesis and WAT browning, suggesting the potential application of calcium in improving obesity-related reproductive disorders.


Assuntos
Tecido Adiposo Marrom/fisiopatologia , Tecido Adiposo Branco/fisiopatologia , Cálcio/administração & dosagem , Ciclo Estral/efeitos dos fármacos , Doenças dos Genitais Femininos/tratamento farmacológico , Infertilidade/tratamento farmacológico , Obesidade/complicações , Termogênese/efeitos dos fármacos , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais/análise , Metabolismo Energético/efeitos dos fármacos , Feminino , Doenças dos Genitais Femininos/etiologia , Doenças dos Genitais Femininos/metabolismo , Doenças dos Genitais Femininos/fisiopatologia , Humanos , Infertilidade/etiologia , Infertilidade/metabolismo , Infertilidade/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
18.
J Ethnopharmacol ; 241: 112006, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31153863

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Montanoa tomentosa Cerv. (MT) is a native plant from Mexico used in traditional medicine as a remedy for reproductive impairments and relaxing effects. In previous studies, it has been shown that the endocrine state could modify the antianxiety-like actions of anxiolytic compounds. Although women are the primary user of MT, no studies have evaluated the potential impact of the endocrine milieu on its anti-anxiety actions. AIMS OF THE STUDY: Ascertain the antianxiety effects of M. tomentosa in rats with different hormonal conditions, and to analyze the participation of the GABAA receptor in ovariectomized rats treated with MT. MATERIALS AND METHODS: The animal model of anxiety used was the elevated plus-maze (EPM). Rats' endocrine conditions were: a) Low hormone levels (rats in diestrus I and II phases); b) High hormone levels (proestrus/estrus phases); c) No hormones (ovariectomized rats); and d) Rats under progesterone withdrawal (PW). To evaluate the participation of the GABAA receptor in the anxiolytic-like action of MT the antagonist picrotoxin was used. RESULTS: Results showed that MT induced dose-dependent anxiolytic-like actions in rats with low hormone level conditions. Also, MT reduced anxiety-like behavior in female rats under PW, in contrast to diazepam which was ineffective. MT's anxiolytic-like effect was blocked by picrotoxin, suggesting the participation of the GABAA receptor complex. However, increased anxiety-like behavior was observed in rats with a high hormone level condition and low doses of MT. CONCLUSIONS: Beneficial anxiolytic-like actions of MT are observed under low hormone conditions, particularly in the PW challenge (a condition that can be related to a premenstrual period). Furthermore, the participation of the GABAA receptor is evidenced. However, hormonal variations could induce the opposite effects, hence women should be cautious.


Assuntos
Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Montanoa , Extratos Vegetais/uso terapêutico , Animais , Ansiolíticos/farmacologia , Ansiedade/sangue , Ansiedade/fisiopatologia , Comportamento Animal/efeitos dos fármacos , Ciclo Estral/efeitos dos fármacos , Feminino , Locomoção/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta , Progesterona/sangue , Ratos Wistar , Receptores de GABA-A/fisiologia
19.
J Pharmacol Exp Ther ; 370(2): 337-349, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31197018

RESUMO

Our previous report examined the pharmacokinetics (PK) of methylprednisolone (MPL) and adrenal suppression after a 50 mg/kg IM bolus in male and female rats, and we described in detail the development of a minimal physiologically based pharmacokinetic/pharmacodynamic (mPBPK/PD) model. In continuation of such assessments, we investigated sex differences in genomic MPL responses (PD). Message expression of the glucocorticoid-induced leucine zipper (GILZ) was chosen as a multitissue biomarker of glucocorticoid receptor (GR)-mediated drug response. Potential time-dependent interplay between sex hormone and glucocorticoid signaling in vivo was assessed by comparing the enhancement of GILZ by MPL in the uterus [high estrogen receptor (ER) density] and in liver (lower ER density) from male and female rats dosed within the proestrus (high estradiol/progesterone) and estrus (low estradiol/progesterone) phases of the rodent estrous cycle. An expanded-systems PD model of MPL considering circadian rhythms, multireceptor (ER and GR) control, and estrous variations delineated the determinants controlling receptor/gene-mediated steroid responses. Hepatic GILZ response was ∼3-fold greater in females, regardless of estrous stage, compared with males, driven predominantly by increased MPL exposure in females and a negligible influence of estrogen interaction. In contrast, GILZ response in the uterus during proestrus in females was 60% of that observed in estrus-phased females, despite no PK or receptor differences, providing in vivo support to the hypothesis of estrogen-mediated antagonism of glucocorticoid signaling. The developed model offers a mechanistic platform to assess the determinants of sex and tissue specificity in corticosteroid actions and, in turn, reveals a unique PD drug-hormone interaction occurring in vivo. SIGNIFICANCE STATEMENT: Mechanisms relating to sex-based pharmacodynamic variability in genomic responses to corticosteroids have been unclear. Using combined experimental and systems pharmacology modeling approaches, sex differences in both pharmacokinetic and pharmacodynamic mechanisms controlling the enhancement of a sensitive corticosteroid-regulated biomarker, the glucocorticoid-induced leucine zipper (GILZ), were clarified in vivo. The multiscale minimal physiologically based pharmacokinetics/pharmacodynamic model successfully captured the experimental observations and quantitatively discerned the roles of the rodent estrous cycle (hormonal variation) and tissue specificity in mediating the antagonistic coregulation of GILZ gene synthesis. These findings collectively support the hypothesis that estrogens antagonize pharmacodynamic signaling of genomic corticosteroid actions in vivo in a time- and estrogen receptor-dependent manner.


Assuntos
Ciclo Estral/efeitos dos fármacos , Metilprednisolona/farmacologia , Metilprednisolona/farmacocinética , Modelos Biológicos , Receptores Estrogênicos/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Animais , Estradiol/sangue , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Metilprednisolona/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Caracteres Sexuais , Fatores de Transcrição/genética
20.
Reprod Toxicol ; 87: 1-7, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31055052

RESUMO

Metformin (MET) is a widely-used drug for the treatment of type 2 diabetes mellitus and gestational diabetes. It is known that metformin crosses the placenta and can to be transferred through milk. In vitro studies show that MET decreases gonadotropin-releasing hormone and gonadotropins release in rat neurons, and decreases progesterone and estradiol in rat granulosa cells and androstenedione synthesis in human theca cells. This study evaluated whether MET maternal exposure might interfere with reproductive parameters of female offspring. Wistar female rats were treated with MET 293 mg/kg/day, by gavage, from gestational day (GD) 0 to GD 21 (METG) or GD 0 until lactation day (LD) 21 (METGL). Controls groups received water. An increase in plasmatic estradiol levels was observed during the estrus stage in the METGL group. This result suggests that exposure to MET during gestational and lactational periods might be related to programming in theca and/or granulosa cells during development.


Assuntos
Hipoglicemiantes/toxicidade , Troca Materno-Fetal , Metformina/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Animais , Comportamento Animal/efeitos dos fármacos , Estradiol/sangue , Ciclo Estral/efeitos dos fármacos , Feminino , Fertilidade/efeitos dos fármacos , Lactação , Comportamento Materno/efeitos dos fármacos , Ovário/efeitos dos fármacos , Gravidez , Ratos Wistar , Maturidade Sexual/efeitos dos fármacos , Útero/efeitos dos fármacos
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