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2.
Zhonghua Fu Chan Ke Za Zhi ; 55(1): 9-14, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-32074767

RESUMO

Objective: To explore and compare the preventive effect of using letrozole and gonadotropin-releasing hormone (GnRH) antagonist during luteal phase of patients at high risk for ovarian hyperstimulation syndrome (OHSS). Methods: A total of 99 infertile women undergoing in vitro fertilization and embryo transfer or intracytoplasmic sperm injection with high risk for OHSS were enrolled in this randomized controlled trial.The letrozole group (n=51) received letrozole of 7.5 mg daily for 3 days;the GnRH antagonist group (n=48) were given cetrorelix of 0.25 mg subcutaneously daily for 3 days. Both groups received support therapy combined with embryo cryopreservation. The incidence of OHSS was surveyed. And the serum concentration of estradiol, LH and progesterone on days 3, 5 and 8 after oocytes retrieval were measured. Results: There were no statistical differences in terms of baseline characteristics of patients and outcomes of controlled ovarian hyperstimulation between the two groups.The incidence of moderate and severe OHSS was found no significantly difference between letrozole group [11.8%(6/51)] and GnRH antagonist group [10.4%(5/48);P>0.05]. The estradiol concentration of the indicated days on days 3,5 and 8 after oocytes retrieval in letrozole group and GnRH antagonist group were (1 417±3 543) versus (15 210±9 921) pmol/L, (1 692±4 330) versus (18 680±11 567) pmol/L, (239±336) versus (3 582±5 427) pmol/L, respectively;compared with GnRH antagonist group, the estradiol level was significantly lower in the letrozole group (all P<0.01). The luteinizing hormone level in the letrozole group were (0.46±0.40), (0.56±0.55)and (0.67±0.58) U/L on days 3,5 and 8 after oocytes retrieval, which were significantly higher than those of GnRH antagonist group [(0.28±0.28), (0.30±0.19) and (0.45±0.37) U/L, respectively; all P<0.05]. There was no obvious differences on progesterone levels between letrozole group and GnRH antagonist group (all P>0.05),and on days 8 after oocytes retrieval,the level of progesterone in each group were significantly lower than those on day 3 and 5 after oocytes retrieval (P<0.05). Conclusion: Letrozole has the same efficiency as GnRH antagonist for the prevention of OHSS, faster and cheaper to use, but its efficacy seems not to be related to the suppression of steroidogenic during the luteal phase.


Assuntos
Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Infertilidade Feminina/terapia , Letrozol/uso terapêutico , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Indução da Ovulação , Estradiol/sangue , Feminino , Fertilização In Vitro , Humanos , Fase Luteal , Hormônio Luteinizante/sangue , Progesterona/sangue
3.
Gen Physiol Biophys ; 39(1): 27-36, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32039822

RESUMO

The G protein-coupled estrogen receptor (GPER) was proved to be a new type of estrogen receptor (ER). It is unknown that whether estrogen can regulate the secretion of gonadotrophin releasing hormone (GnRH) in GT1-7 cells through the mechanism with the involvement of GPER. The GnRH, estradiol (17ß-estradiol, E2) and GPER in peripheral blood of precocious puberty children were detected by ELISA and RT-qPCR assays. After E2 treatment, the levels of GPER and GnRH in GT1-7 cells were detected. Following G1 treatment, cell proliferation was examined using a CCK-8 assay. The levels of GnRH, KISS1, GPR54, nNOS, c-FOS in GT1-7 cells were assessed following GT1-7 cells were induced by E2 combined with G1 or G15. GnRH, E2 and GPER were significantly increased in precocious puberty children. After E2 treatment, GT1-7 cells expressed more GnRH and GPER was markedly elevated and reached a peak at 8 h. The KISS1, GPR54 and nNOS in GT1-7 cells were significantly increased with G1 induction, but were significantly decreased with G15 induction compared with E2 induction alone. Collectively, GPER cannot promote the release of GnRH via affecting the proliferation of GT1-7 cells, but it may regulate GnRH through KISS1/GPR54 pathway, which provides novel ideas for precocious puberty children treatment.


Assuntos
Puberdade Precoce , Animais , Linhagem Celular , Estradiol , Estrogênios , Hormônio Liberador de Gonadotropina , Camundongos , Receptores Estrogênicos , Receptores Acoplados a Proteínas-G
4.
Br J Radiol ; 93(1108): 20190577, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31944823

RESUMO

OBJECTIVE: It has been established that survival and toxicity outcomes in some cancer types could be influenced by haemoglobin (Hb) levels. This study aims to determine if pre-treatment Hb is associated with late toxicity or survival outcomes in prostate cancer. METHODS: Data from one Phase III randomised controlled trial and one single arm translational trial were analysed. Patients had localized prostate cancer and received ≥70 Gy radiotherapy and neo-adjuvant androgen deprivation between 1997 and 2013. RESULTS: 302 males were included. Median follow-up was 6.8 years for toxicity and 10.3 years for survival outcomes. Patients with Hb below the reference range were more likely to experience Grade 2-3 late gastrointestinal toxicity than patients with Hb within the range (p = 0.050). Neither late genitourinary toxicity, erectile function toxicity, prostate-specific antigen relapse free survival nor overall survival of patients were statistically significantly different between groups. CONCLUSION: Anaemia in prostate cancer is found in the minority of patients and is usually mild. Prostate cancer patients undergoing radiotherapy with low Hb were more likely to experience Grade 2-3 late gastrointestinal toxicity. ADVANCES IN KNOWLEDGE: This study is one of the first in the published literature to investigate the role of Hb in prostate cancer toxicity and survival. We have found an association between Hb below the reference range and late GI toxicity. Consideration should be given to further investigating patients with iron deficiency anaemia to guide management options and outrule underlying GI pathology before proceeding with radiotherapy treatment.


Assuntos
Anemia/sangue , Hemoglobina A/análise , Órgãos em Risco/efeitos da radiação , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Trato Gastrointestinal/efeitos da radiação , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Ereção Peniana , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/tratamento farmacológico , Valores de Referência , Estudos Retrospectivos
6.
N Engl J Med ; 382(4): 328-340, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31971678

RESUMO

BACKGROUND: Uterine fibroids are hormone-responsive neoplasms that are associated with heavy menstrual bleeding. Elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, may reduce fibroid-associated bleeding. METHODS: We conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to evaluate the efficacy and safety of elagolix at a dose of 300 mg twice daily with hormonal "add-back" therapy (to replace reduced levels of endogenous hormones; in this case, estradiol, 1 mg, and norethindrone acetate, 0.5 mg, once daily) in women with fibroid-associated bleeding. An elagolix-alone group was included to assess the impact of add-back therapy on the hypoestrogenic effects of elagolix. The primary end point was menstrual blood loss of less than 80 ml during the final month of treatment and at least a 50% reduction in menstrual blood loss from baseline to the final month; missing data were imputed with the use of multiple imputation. RESULTS: A total of 412 women in UF-1 and 378 women in UF-2 underwent randomization, received elagolix or placebo, and were included in the analyses. Criteria for the primary end point were met in 68.5% of 206 women in UF-1 and in 76.5% of 189 women in UF-2 who received elagolix plus add-back therapy, as compared with 8.7% of 102 women and 10% of 94 women, respectively, who received placebo (P<0.001 for both trials). Among the women who received elagolix alone, the primary end point was met in 84.1% of 104 women in UF-1 and in 77% of 95 women in UF-2. Hot flushes (in both trials) and metrorrhagia (in UF-1) occurred significantly more commonly with elagolix plus add-back therapy than with placebo. Hypoestrogenic effects of elagolix, especially decreases in bone mineral density, were attenuated with add-back therapy. CONCLUSIONS: Elagolix with add-back therapy was effective in reducing heavy menstrual bleeding in women with uterine fibroids. (Funded by AbbVie; Elaris UF-1 and Elaris UF-2 ClinicalTrials.gov numbers, NCT02654054 and NCT02691494.).


Assuntos
Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hidrocarbonetos Fluorados/uso terapêutico , Leiomioma/complicações , Menorragia/tratamento farmacológico , Pirimidinas/uso terapêutico , Adulto , Densidade Óssea/efeitos dos fármacos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Fogachos/induzido quimicamente , Humanos , Hidrocarbonetos Fluorados/efeitos adversos , Menorragia/etiologia , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários
8.
J Korean Med Sci ; 35(4): e47, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31997617

RESUMO

BACKGROUND: The objective of this study was to investigate whether androgen deprivation therapy (ADT) with gonadotropin-releasing hormone agonist (GnRHa) in prostate cancer (Pca) patients is associated with cardiovascular disease in the cohort based from the entire Korean population. METHODS: Using the Korean National Health Insurance database, we conducted an observational study of 579,377 men who sought treatment for Pca between January 1, 2012 and December 31, 2016. After excluding patients with previously diagnosed cardiovascular disease or who had undergone chemotherapy, we extracted the data from 2,053 patients who started GnRHa (GnRHa users) and 2,654 men who were newly diagnosed with Pca (GnRHa nonusers) between July 1, 2012, and December 31, 2012, with follow-up through December 31, 2016. The primary outcomes were cerebrovascular attack (CVA) and ischemic heart disease (IHD). RESULTS: GnRHa users were older, were more likely to reside in rural areas, had lower socioeconomic status, and had more comorbidities than nonusers (all P < 0.050). Although GnRHa users had an increased incidence of CVA and IHD (P = 0.013 and 0.048, respectively) in univariate analysis, GnRHa use was not associated with the outcomes in multivariate analysis. Furthermore, the cumulative duration of ADT was not associated with the outcomes whereas the associations between age at diagnosis with all diseases were significant. CONCLUSION: Our complete enumeration of the Korean Pca population shows that ADT is not associated with increased risks of cardiovascular disease.


Assuntos
Antagonistas de Androgênios , Doenças Cardiovasculares , Hormônio Liberador de Gonadotropina , Neoplasias da Próstata , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/tratamento farmacológico , Fatores de Risco
9.
Food Chem Toxicol ; 135: 110897, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31654709

RESUMO

The mechanisms of prenatal cadmium (Cd) exposure cause adverse effect transmission to future generations that remain unclear. In this study, pregnant SD rats were orally dosed with Cd (0, 0.5, 2.0, and 8.0 mg/kg/day) from gestation day 1 until birth. F1 female rats were mated with untreated males for F2 generation. In both generations, after prenatal Cd exposure, histopathological examinations showed testicular development disorder. A significant decrease in serum testosterone (T) was observed in the F1 rats, but a significant increase in serum T was observed in the F2 rats. Moreover, both the F1 and F2 rats had different patterns of mRNA and protein expression for testicular steroidogenic factor 1 (SF-1) and steroidogenic enzymes at postnatal days (PNDs) 21 and 56. We also found that rno-miR-328a-5 and rno-miR-10b-5p significantly changed and TargetScan software showed that both of these microRNAs targeted SF-1 and steroidogenic acute regulatory (StAR), respectively. Overall, the results indicate that prenatal Cd exposure causes male reproductive problems in a multigenerational manner. In addition, SF-1 signaling was disrupted and the expressions of microRNAs were affected, which may be an important target for Cd-induced reproductive toxicity in offspring.


Assuntos
Cádmio/toxicidade , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator Esteroidogênico 1/metabolismo , Testosterona/metabolismo , Animais , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Luteinizante/metabolismo , Masculino , Exposição Materna/efeitos adversos , MicroRNAs/metabolismo , Gravidez , Progesterona/metabolismo , Ratos Sprague-Dawley , Testículo/patologia
10.
Zoo Biol ; 39(1): 23-28, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31617256

RESUMO

The objective of this study was to investigate variation in sperm quality metrics (motility, velocity, and concentration) in the critically endangered Mississippi gopher frog (Lithobates sevosus) over three sampling time points after a luteinizing hormone-releasing hormone analog (LHRHa) induction injection. Sperm was repeatedly collected from 11 individuals over three sampling times (30, 60, and 120 min) after injection. Variation in sperm quality was investigated using a repeated-measures mixed model approach. Repeated measures analyses of variance showed a significant effect of sampling time for percent motility and velocity. Concentration was found to be marginally related to sampling time, while progressive motility was not significantly related to time after injection. Our findings are important for optimizing assisted reproduction-related fertilization success and increasing the successful propagation of endangered species of imperiled frogs in captive breeding programs.


Assuntos
Hormônio Liberador de Gonadotropina/farmacologia , Ranidae/fisiologia , Espermatozoides/efeitos dos fármacos , Animais , Espécies em Perigo de Extinção , Hormônio Liberador de Gonadotropina/administração & dosagem , Masculino , Espermatozoides/fisiologia
11.
Gen Comp Endocrinol ; 285: 113250, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31445009

RESUMO

Seasonally breeding animals initiate gonadal recrudescence when mechanisms that suppress reproduction give way to mechanisms that stimulate it. However, knowledge of mechanistic changes in hormonal regulation during this transition is limited. Further, most studies of reproductive timing have focused on males, despite the critical role of females in determining breeding phenology. Closely related populations that live in the same environment but differ in reproductive timing provide an opportunity to examine differences in mechanisms during the transition from the pre-reproductive to reproductive state. We studied closely related migrant and resident populations of dark-eyed juncos (Junco hyemalis) that reside in the same environment in spring but differ in breeding phenology. Residents initiate breeding earlier than migrants, which do not breed until after they have migrated. To directly study differences in the hypothalamic mechanisms of reproduction, we captured 16 migrant and 13 resident females from the field on March 25-April 11. We quantified expression of mRNA transcripts and show that resident females had higher abundance of gonadotropin-releasing hormone transcripts than migrant females, indicating greater reproductive development in resident than migrant females living in the same environment. We also found higher transcript abundance of estrogen receptor and androgen receptor in migrant than resident females, suggesting that negative feedback may delay reproductive development in migrant females until after they migrate. These differences in hypothalamic mechanisms may help to explain differences in reproductive timing in populations that differ in migratory strategy.


Assuntos
Migração Animal/fisiologia , Sistemas Neurossecretores/metabolismo , Estações do Ano , Aves Canoras/fisiologia , Simpatria/fisiologia , Animais , Feminino , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Modelos Lineares , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
12.
Theriogenology ; 141: 211-218, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31387698

RESUMO

Castration reduces aggressive and sexual behaviour and provides better carcass quality in bull calves. Vaccination against gonadotrophin-releasing hormone (GnRH) is used as an alternative to surgical castration for the purposes of reducing pain and distress in the animals. Currently, no anti-GnRH vaccine has been authorized for use in cattle in the European Union. The aim of the present study was to assess the effect of an anti-GnRH swine-specific vaccine (Improvac®, Zoetis, USA) on the morphology, structure and function of bull testes. Animals were vaccinated at days 1, 21 and 104 of the experimental period and were classified based on their live weight into the following two groups: LIGHT (172.9 ±â€¯30.00 kg) and HEAVY (323.8 ±â€¯37.79 kg). The scrotal circumference was measured on day 1 and prior to slaughter (day 164). At slaughter, the sperm motility and concentration in the caudae epididymis were assessed. Testes were weighed, measured and examined using ultrasound, and then tissue samples were collected and fixed in formalin. Histological and immunohistochemical studies were performed on the testes to measure the diameter of the seminiferous tubules and assess the testicular cell populations. The results revealed that suppression of testicular development was associated with the use of the Improvac® vaccine, which resulted in a smaller size of the testes and impaired spermatid production. However, the effect of Improvac® was more pronounced and consistent in calves vaccinated at a low live weight than at a heavy live weight, which suggested that vaccination is more effective when calves are vaccinated before or early during puberty. However, testes from calves vaccinated at a low live weight were more prone to the development of intraluminal concretions in the seminiferous tubules.


Assuntos
Hormônio Liberador de Gonadotropina/imunologia , Orquiectomia/métodos , Testículo/anatomia & histologia , Vacinas Anticoncepcionais/imunologia , Animais , Bovinos , Masculino , Tamanho do Órgão/imunologia , Escroto/anatomia & histologia , Espermatozoides/fisiologia , Vacinação
13.
Theriogenology ; 141: 105-112, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31536859

RESUMO

We hypothesized that a shortened version of a modified Ovsynch program (OVS: GnRH-1 - 7 d - PGF2α-1 - 24 h - PGF2α-2 - 32 h - GnRH-2 - 16 h - AI) that excluded GnRH-1 to resynchronize ovulation in cows bearing a corpus luteum (CL) after a non-pregnancy diagnosis (NPD) or including progesterone supplementation with the OVS treatment for cows without a CL would produce shorter inter-insemination intervals and pregnancy per AI (P/AI) not different from that of cows treated with the OVS treatment. Of the 1697 lactating Holstein cows enrolled in this experiment, complete data were available for only 1584 cows because the remainder was not treated, inseminated per treatment design, left the herd before pregnancy diagnosis, or some other outcome was missing. Cows were enrolled in the study and assigned to either of three treatments at NPD (32 ±â€¯3 d after AI [Day 0]). Cows with a detected CL were assigned randomly to: (1) a modified Ovsynch (OVS; GnRH-1 - 7 d - PGF2α-1 - 24 h - PGF2α-2 - 32 h - GnRH-2 - 16 h - AI) or (2) Short Synch (SS; PGF2α-1 - 24 h - PGF2α-2 - 32 h - GnRH-2 - 16 h - AI). Cows with no CL were assigned to OVS plus a progesterone insert (CIDR). Blood was collected at NPD to measure progesterone concentration and determine accuracy of treatment assignment (progesterone ≥ 1 ng/mL for a functional CL). Overall progesterone concentration at NPD was less in OVS + CIDR cows (1.5 ± 0.3 ng/mL) than in OVS (5.2 ± 0.2 ng/mL) or SS cows (3.7 ± 0.3 ng/mL). No differences in luteolytic risk (progesterone < 0.5 ng/mL at 72 h after PGF2α-1) were detected after PGF2α (>96.7%) and ovulation risk after GnRH-2 was 93.8, 91.7, and 86.2% for SS, OVS, and OVS + CIDR, respectively. Mean and median inter-insemination interval were less in SS (mean = 34.3 ± 0.05 d [median = 35 d] than OVS cows (40.2 ± 0.05 d [42 d]), but that in OVS cows did not differ from OVS + CIDR cows (41.4 ± 0.05 d [42 d]). Technicians were more accurate in visually detecting a functional CL than a non-functional CL (81.2 vs. 61.1%). Sensitivity of detecting a functional CL by technicians averaged 91.2%, but specificity was 39.8%. Pregnancy per AI at 32 ± 3 d after AI was less for SS (16.5% [n = 115]) than OVS (29.3% [n = 133] when a functional CL was inaccurately detected, but did not differ when a functional CL was detected accurately (27.6% [n = 561] vs 30.3% [508]). Pregnancy per AI did not differ between OVS and OVS + CIDR cows regardless of CL status. Short synch is an alternative to the entire modified Ovsynch program to produce similar P/AI when the CL status was detected accurately, and regardless of functional CL status, SS reduced inter-insemination intervals by 7 d.


Assuntos
Bovinos , Corpo Lúteo , Dinoprosta/farmacologia , Sincronização do Estro/métodos , Hormônio Liberador de Gonadotropina/farmacologia , Inseminação Artificial/veterinária , Animais , Dinoprosta/administração & dosagem , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Gravidez
14.
Theriogenology ; 141: 197-201, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31563861

RESUMO

To minimize costs and labor for short-term ovulation synchronization protocol, we developed one wherein each treatment-drug administration and timed artificial insemination (TAI)-was performed 24 h apart. The objective of the present study was to evaluate this short-term ovulation synchronization protocol in lactating dairy cows. Data were derived from 133 inseminations performed in 120 cows (32 primiparous and 88 multiparous), and the ovaries of these cows were scanned using ultrasound. The cows detected to have a functional corpus luteum (CL) received prostaglandin F2α (PGF) as a luteolytic agent. The cows were randomly assigned to two treatment groups: (1) treatment with estradiol benzoate (EB) 24 h after PGF treatment, and TAI 24-28 h after EB treatment (EB group); and (2) treatment with gonadotropin-releasing hormone agonist (GnRH) 56 h after PGF treatment, and TAI 16-20 h after GnRH treatment (GnRH group). As a luteolytic agent, either dinoprost (DP; 25 mg) or D-cloprostenol (DCLP; 0.15 mg) was administered intramuscularly in each treatment group. Pregnancy per AI (P/AI) was significantly higher in the DP- or DCLP-treated cows in the EB group when compared with their counterparts in the GnRH group (64.5% vs. 33.3%, P = 0.03 in the DP-treated cows and 51.1% vs. 27.3%, P = 0.04 in the DCLP-treated cows, respectively). Regarding parity, multiparous cows had greater P/AI in the EB group than in the GnRH group (52.8% vs. 26.7%, P = 0.01), whereas primiparous cows showed no significant intergroup difference (65.2% vs. 41.7%, P = 0.28). To conclude, the use of a convenient synchronization protocol comprising the administration of PGF and EB 24 h apart, rather than PGF and GnRH 56 h apart, has greater potential to improve pregnancy rates after TAI in lactating dairy cows given that a functional CL was accurately detected. This beneficial effect of the protocol using EB was clearly demonstrated in multiparous cows.


Assuntos
Dinoprosta/farmacologia , Estradiol/análogos & derivados , Sincronização do Estro/efeitos dos fármacos , Inseminação Artificial/veterinária , Animais , Bovinos , Dinoprosta/administração & dosagem , Estradiol/administração & dosagem , Estradiol/farmacologia , Sincronização do Estro/métodos , Feminino , Hormônio Liberador de Gonadotropina/farmacologia , Inseminação Artificial/métodos , Paridade , Gravidez , Estações do Ano
15.
Theriogenology ; 141: 202-210, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31606718

RESUMO

The present study tested the hypothesis that administration of GnRH on day 5 of the estrous cycle in embryo transfer (ET) recipients would increase progesterone (P4) concentrations, embryo size, and improve fertility. Holstein and cross-bred Holstein heifers (n = 1562) were synchronized using a modified 5-day CIDR-Synch protocol as follows (All AM treatments): D-8, CIDR inserted; D-3, CIDR removed and PGF2α (500 µg cloprostenol) treatment; D-2, second PGF2α; D0, GnRH (G1, 100 µg gonadorelin acetate) to induce ovulation. On D5 in the afternoon, heifers were assigned in a completely randomized design to one of two treatments: Control (untreated) or GnRH (200 µg). Transfer of day 7 fresh IVP embryos was performed between D6 and D8 after G1. Data collected from each heifer included: embryo stage and quality, body condition score, technician performing ET, interval from G1 to ET, and number of previous transfers. All heifers were evaluated by transrectal ultrasonography on D5, D33, and D60 and a subset of heifers was scanned on D12 (n = 718; to determine ovulation to treatment) and another subset on D33 (n = 295; 16 s video to determine embryo and amniotic vesicle size). Serum P4 was determined from a subset of heifers on D12 (n = 467) and on D21 (n = 837) and pregnancy specific protein B (PSPB) on D28 (n = 843). Pregnancies per ET (P/ET) were analyzed by logistic regression and continuous outcomes by ANOVA. Ovulation to D5 GnRH, defined by the presence of an accessory CL on D12, was 83.9% (302/360) in GnRH-treated heifers vs. 3.3% (12/358) in Controls (P < 0.001). On D12, P4 was greater (P < 0.001) in GnRH-treated heifers (7.2 ±â€¯0.1 ng/ml) vs Controls (6.0 ±â€¯0.1 ng/ml). There was greater P/ET at D33 and D60 of pregnancy for Stage 7 than Stage 6 embryos. Treatment with GnRH did not alter P/ET with either embryo stage but decreased pregnancy loss between D33 and D60 in heifers receiving Stage 7 embryos. Presence of an accessory CL at the D33 pregnancy diagnosis was associated with a larger reduction in pregnancy loss from D33 to D60 in recipients of Stage 7 embryos (11.6 vs 27.6%). Although there was no GnRH effect on embryo size, the presence of an accessory CL was associated (P < 0.05) with larger amniotic vesicle volume in recipients of Stage 7 embryos. In addition, greater PSPB was linked to greater amniotic vesicle volume (P = 0.01) and to reduced pregnancy loss (P < 0.0001). In conclusion, treatment with GnRH on D5 caused ovulation and formation of an accessory CL, increased circulating P4, and reduced pregnancy loss in heifers receiving a Stage 7 but not a Stage 6 IVP embryo.


Assuntos
Aborto Animal/prevenção & controle , Blastocisto/fisiologia , Bovinos , Transferência Embrionária/veterinária , Hormônio Liberador de Gonadotropina/farmacologia , Ovulação/efeitos dos fármacos , Animais , Dinoprosta/administração & dosagem , Dinoprosta/farmacologia , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Ovulação/fisiologia , Gravidez , Proteínas da Gravidez/sangue , Progesterona/sangue
16.
Ecotoxicol Environ Saf ; 188: 109898, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31711775

RESUMO

Gamma-aminobutyric acid (GABA) plays a critical role in regulation of gonadotropin-releasing hormone (GnRH) through GABAA receptor (GABAAR). Nitric oxide (NO) production has correlation with GABA and regulates GnRH secretion. This study was performed to examine the mechanisms by which manganese (Mn) accelerate puberty onset involves GABAAR/NO pathway in the preoptic area-anterior hypothalamus (POA-AH) in immature female rats. First, female rats received daily dose of MnCl2 0 (saline), 2.5, 5 and 10 mg/kg b.w by oral gavage during postnatal day (PND) 21-32. Animals administered with 10 mg/kg MnCl2 exhibited earlier puberty onset age and advanced ovary and uterus development than these in saline-treatment group. Furthermore, we found that decrease of GABAAR result in elevated production of nitric oxide synthase1 (NOS1), NO and GnRH in the POA-AH. Second, we recorded the neuronal spikes alternation after perfusion with GABAAR inhibitor bicuculline (BIC), GABAAR agonist isoguvacine (isog), and MnCl2 from the POA-AH in acute brain slices of PND21 rats. Spontaneous firing revealed a powerful GABAAR-mediated action on immature POA-AH and confirm that MnCl2 has a significant effect on GABAAR. Third, we revealed that decrease in NOS1 and NO production by treatment with isog-alone or isog+MnCl2 contribute to the decrease of GnRH in the POA-AH and a delayed puberty onset age compared to treatment with MnCl2-alone. Together, these results suggested that excessive exposure to MnCl2 stimulates NO production through decreased GABAAR in the POA-AH to advance puberty onset in immature female rats.


Assuntos
Envelhecimento/efeitos dos fármacos , Cloretos/toxicidade , Disruptores Endócrinos/toxicidade , Óxido Nítrico/metabolismo , Área Pré-Óptica/efeitos dos fármacos , Receptores de GABA-A/metabolismo , Maturidade Sexual/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Compostos de Manganês , Neurônios/efeitos dos fármacos , Ovário/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Área Pré-Óptica/crescimento & desenvolvimento , Área Pré-Óptica/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Útero/diagnóstico por imagem , Útero/efeitos dos fármacos , Desmame
17.
Endocrinology ; 161(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31875912

RESUMO

Changes in gonadotropin-releasing hormone (GnRH) release frequency from the brain help drive reproductive cycles. In polycystic ovary syndrome (PCOS), persistent high GnRH/luteinizing hormone (LH) frequency disrupts cycles and exacerbates hyperandrogenemia. Adult prenatally-androgenized (PNA) mice exhibit increased GnRH neuron firing rate, elevated ovarian androgens, and disrupted cycles, but before puberty, GnRH neuron activity is reduced in PNA mice compared with controls. We hypothesized that ovarian feedback mediates the age-dependent change in GnRH neuron firing rate in PNA vs control mice. Extracellular recordings of green fluorescent protein (GFP)-identified GnRH neurons were made 5 to 7 days after sham-surgery, ovariectomy (OVX), or, in adults, after OVX plus replacement of sub-male androgen levels with dihydrotestosterone implants (OVX + DHT). In 3-week-old mice, OVX did not affect GnRH neuron firing rate in either group. In adult controls, OVX increased GnRH neuron firing rate, which was further enhanced by DHT. In adult PNA mice, however, OVX decreased GnRH neuron firing rate, and DHT restored firing rate to sham-operated levels. In contrast to the differential effects of ovarian feedback on GnRH neuron firing rate, serum LH increased after OVX in both control and PNA mice and was not altered by DHT. Pituitary gene expression largely reflected changes expected with OVX, although in PNA but not control mice, DHT treatment increased Lhb expression. These results suggest prenatal androgen exposure programs marked changes in GnRH neuron regulation by homeostatic steroid feedback. PNA lowers GnRH neuron activity in low-steroid states (before puberty, OVX), and renders activity in adulthood dependent upon ongoing exposure to elevated ovarian androgens.


Assuntos
Androgênios/farmacologia , Hormônio Liberador de Gonadotropina/metabolismo , Neurônios/fisiologia , Ovário/metabolismo , Animais , Di-Hidrotestosterona/farmacologia , Eletrofisiologia , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ovariectomia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Maturidade Sexual/fisiologia
18.
Int J Gynaecol Obstet ; 148(1): 59-64, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31569274

RESUMO

OBJECTIVE: To compare the effect of gonadotropin-releasing hormone (GnRH) agonist microdose flare-up and GnRH agonist flare-up protocols among women with poor ovarian reserve undergoing intracytoplasmic sperm injection (ICSI) cycles. METHODS: Randomized controlled trial study among 131 women with poor ovarian reserve who underwent ICSI cycles at a single center in Tehran, Iran, between September 2008 and May 2014. Eligible women were randomly assigned to either the microdose flare-up (n=66) or flare-up (n=65) protocol. The primary outcome measure was live birth rate. RESULTS: Both groups were comparable in cycle cancellation, mean number of dominant follicles, retrieved oocytes, and metaphase II oocytes. Number of stimulation days (P=032) and endometrial thickness (P=0.001) were significantly higher, and gonadotropin dose was non-significantly higher (P=0.075) in the microdose flare-up group than in the flare-up group. No difference in clinical pregnancy, implantation, or abortion rate was observed between the two protocols. Live birth was higher in the microdose flare-up group than in the flare-up group (P=0.036). CONCLUSION: The microdose flare-up protocol seemed to be superior to the flare-up protocol, but it required a higher dose of gonadotropins and a longer duration of stimulation. Further prospective clinical trials of the microdose flare-up protocol are recommended. CLINICALTRIALS.GOV: NCT01006954.


Assuntos
Hormônio Liberador de Gonadotropina/agonistas , Antagonistas de Hormônios/administração & dosagem , Indução da Ovulação/métodos , Injeções de Esperma Intracitoplásmicas/métodos , Adulto , Coeficiente de Natalidade , Relação Dose-Resposta a Droga , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Antagonistas de Hormônios/farmacologia , Humanos , Irã (Geográfico) , Nascimento Vivo , Recuperação de Oócitos/estatística & dados numéricos , Gravidez
19.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(10): 1207-1212, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31801718

RESUMO

OBJECTIVE: To compare the effects of cetrorelix and ganirelix in gonadotropin-releasing hormone antagonist (GnRH-ant) cycles for preventing premature luteinizing hormone (LH) surges and on clinical outcomes of IVF-ET cycles. METHODS: We retrospectively analyzed 2572 GnRH-ant cycles of in vitro fertilization and embryo transfer from January, 2013 to December, 2016, including 1368 cycles with cetrorelix treatment and 1204 cycles with ganirelix treatment. The baseline characteristics of the patients and the clinical outcomes of the two groups were compared. RESULTS: Compared with those receiving ganirelix treatment, the patients with cetrorelix treatment had a significantly younger age (33.10 vs 33.89 years, P < 0.001) and a lower body mass index (21.57 vs 21.84 kg/m2, P=0.024). After adjustment for age and body mass index of the patients, no significant differences were found between the two groups in the levels of follicle-stimulating hormone (FSH), LH, estradiol (E2), progesterone (P) levels either at the baseline or on the day of hCG triggering, or in the number of oocytes retrieved (P > 0.05). The two groups also had comparable percentages of patients with LH > 10 U/L on the day of hCG triggering (3.7% vs 3.2%) and similar spontaneous ovulation rate (0.6% vs 0.5%), clinical pregnancy rate (47.7% vs 45.9%) and live birth rate (37.5% vs 33.6%) following fresh embryo transfer (P > 0.05). The incidence of moderate to severe ovarian hyperstimulation syndrome, however, was significantly higher in ganirelix group than in cetrorelix group (0.7% vs 0.1%, P=0.006). CONCLUSIONS: Cetrorelix and ganirelix can achieve comparable effects for preventing premature LH surges and can achieve similar clinical outcomes of GnRH-ant cycles, but ganirelix is associated with a significantly higher incidence of moderate to severe ovarian hyperstimulation syndrome.


Assuntos
Fertilização In Vitro , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Antagonistas de Hormônios/uso terapêutico , Hormônio Luteinizante/fisiologia , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Hormônio Luteinizante/sangue , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Resultado do Tratamento
20.
PLoS One ; 14(12): e0227095, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31887207

RESUMO

We hypothesized that heat-induced perturbations in cumulus cells surrounding the maturing oocyte may extend to the mural granulosa of the periovulatory follicle in the heat-stressed cow to subsequently the follicular fluid proteome. Lactating Holsteins were pharmacologically stimulated to have a dominant follicle that was capable of responding to a gonadotropin releasing hormone-induced luteinizing hormone surge. Following gonadotropin releasing hormone administration, cows were maintained at ~67 temperature humidity index (THI; thermoneutral conditions) or exposed to conditions simulating an acute heat stress event (71 to 86 THI; heat stress for ~12 h). Dominant follicle collection was conducted in the periovulatory period ~16 h after gonadotropin releasing hormone. Follicular fluid proteome from thermoneutral (n = 5) and hyperthermic (n = 5) cows was evaluated by quantitative tandem mass spectrometry (nano LC-MS/MS). We identified 35 differentially-abundant proteins. Functional annotation revealed numerous immune-related proteins. Subsequent efforts revealed an increase in levels of the proinflammatory mediator bradykinin in follicular fluid (P = 0.0456) but not in serum (P = 0.9319) of hyperthermic cows. Intrafollicular increases in transferrin (negative acute phase protein) in hyperthermic cows (P = 0.0181) coincided with a tendency for levels to be increased in the circulation (P = 0.0683). Nine out of 15 cytokines evaluated were detected in follicular fluid. Heat stress increased intrafollicular interleukin 6 levels (P = 0.0160). Whether hyperthermia-induced changes in the heat-stressed cow's follicular fluid milieu reflect changes in mural granulosa, cumulus, other cell types secretions, and/or transudative changes from circulation remains unclear. Regardless of origin, heat stress/hyperthermia related changes in the follicular fluid milieu may have an impact on components important for ovulation and competence of the cumulus-oocyte complex contained within the periovulatory follicle.


Assuntos
Células do Cúmulo/metabolismo , Líquido Folicular/metabolismo , Transtornos de Estresse por Calor/fisiopatologia , Ovulação/fisiologia , Proteoma/análise , Criação de Animais Domésticos , Animais , Bradicinina/análise , Bradicinina/metabolismo , Bovinos , Células do Cúmulo/efeitos dos fármacos , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Transtornos de Estresse por Calor/etiologia , Temperatura Alta/efeitos adversos , Lactação/fisiologia , Ovulação/efeitos dos fármacos , Proteoma/metabolismo , Proteômica , Tennessee , Transferrina/análise , Transferrina/metabolismo
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