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1.
Vet Clin North Am Food Anim Pract ; 37(1): 125-137, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33541694

RESUMO

Estrus synchronization and manipulation are a tool that has been used by producers to provide uniform lamb and kid meat production and dairy sheep and goat milk production, to concentrate work and labor cost, and to plan for the lambing and kidding time. Breeders can also use estrus synchronization to stimulate ewes and does to exhibit estrus and ovulate outside of the breeding season, although both the ovulation rate and pregnancy rate may be decreased. To increase the ovulation rate outside of the breeding season, a variety of estrus synchronization methods have been used.


Assuntos
Sincronização do Estro/métodos , Cabras/fisiologia , Ovinos/fisiologia , Criação de Animais Domésticos/métodos , Animais , Feminino , Ovulação/efeitos dos fármacos , Gravidez , Taxa de Gravidez , Estações do Ano
2.
J Steroid Biochem Mol Biol ; 208: 105823, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33484844

RESUMO

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


Assuntos
Autofagia/efeitos dos fármacos , Benzoquinonas/farmacologia , Mifepristona/farmacologia , Síndrome do Ovário Policístico/tratamento farmacológico , Receptores Androgênicos/genética , Androgênios/metabolismo , Animais , Autofagia/genética , Proteína Beclina-1/genética , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células da Granulosa/efeitos dos fármacos , Humanos , Resistência à Insulina/genética , Ovário/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Ovulação/efeitos dos fármacos , Ovulação/genética , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/patologia , Ratos , eIF-2 Quinase/genética
3.
Medicine (Baltimore) ; 99(20): e20199, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443342

RESUMO

INTRODUCTION: Resistance ovary syndrome (ROS) is a disease characterized by hypergonadotropic amenorrhea but with normal ovarian reserve. Currently, its pathogenesis is still unclear and the treatment methods are complex. Nevertheless, there are evident negative effects of this disease on females' physical and mental health such as gonadal dysplasia, infertility, anxiety, and depression. This article reports a case of successful ovulation induction and pregnancy with letrozole combined with HMG. This can provide clinical treatment guidelines for the disease. PATIENT CONCERNS: The patient underwent several hormone replacement cycles and ovulation induction cycles. But the dominant follicles were not extracted even after using large doses of gonadotropin. DIAGNOSIS: Resistant ovary syndrome; Primary infertility INTERVENTIONS:: Larger doses of letrozole combined with HMG were injected to stimulate ovulation and sensitize the ovaries during menstruation. This helped to examine the peripheral effects of letrozole in relation to gonadotropin. OUTCOMES: The patient displayed a dominant follicular growth and notable ovulation which resulted in a full-term pregnancy and successful delivery. CONCLUSIONS: The resistance ovary syndrome (ROS) can be treated and the findings from this case provides a possible treatment for ROS patients with infertility.


Assuntos
Inibidores da Aromatase/uso terapêutico , Letrozol/uso terapêutico , Insuficiência Ovariana Primária/tratamento farmacológico , Adulto , Inibidores da Aromatase/administração & dosagem , Quimioterapia Combinada/métodos , Feminino , Gonadotropinas/uso terapêutico , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/tratamento farmacológico , Injeções Intramusculares/métodos , Letrozol/administração & dosagem , Nascido Vivo , Ovulação/efeitos dos fármacos , Ovulação/fisiologia , Indução da Ovulação/métodos , Gravidez , Resultado do Tratamento
4.
Arch Gynecol Obstet ; 301(3): 845-850, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32112181

RESUMO

OBJECTIVE: To detect whether amlodipine could increase pre-ovulatory follicular blood flow, thus enhancing ovulation and creating a better chance of conception in women with PCOS. METHODS: 165 women were screened of which 124 were qualified and women were equally randomized to 62 receiving clomiphene citrate and amlodipine and 62 receiving clomiphene citrate and placebo. The primary outcome was to detect if amlodipine can improve pre-ovulatory follicle blood flow studied by colour and power Doppler Pulsatility index of ovarian arteries, with drug administration. The secondary outcomes were endometrial thickness and clinical pregnancy. RESULTS: The mean value of the ovarian arteries Pulsatility Index was significantly lower in the amlodipine group when compared to those of the placebo group (1.36 and 1.82, respectively, with P value 0.002). Mean endometrial thickness, for all women in both groups, on the day of detecting a mature follicle was significantly higher in the amlodipine group compared to the placebo group (8.99 and 7.0, respectively, with P value 0.003), and clinical pregnancy increased from 11% to 37% in the amlodipine group compared to the placebo group. CONCLUSION: Amlodipine improves ovarian blood flow and increases the chances of conception. TRIAL REGISTRATION: Pan African Clinical Trial Registry (http://www.pactr.org). Trial No: PAC TR201708002485292.


Assuntos
Anlodipino/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Clomifeno/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Hemodinâmica/efeitos dos fármacos , Infertilidade Feminina/tratamento farmacológico , Folículo Ovariano/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Adulto , Anlodipino/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Clomifeno/farmacologia , Método Duplo-Cego , Feminino , Humanos , Síndrome do Ovário Policístico/complicações , Gravidez , Estudos Prospectivos
5.
Endocrinology ; 161(4)2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32141513

RESUMO

Follicle-stimulating hormone (FSH)-induced growth of ovarian follicles is independent of follicular vascularization. Recent evidence has indicated that follicular vascularization is critical to ovarian follicle development and survival. FSH, a gonadotropin that induces follicular growth and development, also acts as the major survival factor for antral follicles. FSH has been reported to stimulate angiogenesis in the theca layers mediated in part by the vascular endothelial growth factor A (VEGFA) and the transcription factor hypoxia inducible factor 1α (HIF-1α). However, it remains largely undetermined whether FSH-dependent growth and survival of antral follicles relies on FSH-induced vascularization. Here, we first demonstrated that induction of angiogenesis through the FSH-HIF-1α-VEGFA axis is not required for FSH-stimulated follicular growth in mouse ovary. FSH increased the total number of blood vessels in mouse ovarian follicles, which was correlated with elevated expression of VEGFA and HIF-1α in granulosa cells. In contrast, blocking of follicular angiogenesis using inhibitors against the HIF-1α-VEGFA pathway repressed vasculature formation in follicles despite FSH administration. Interestingly, by measuring follicular size and ovarian weight, we found that the suppression of angiogenesis via HIF-1α-VEGFA pathway did not influence FSH-mediated follicular growth. However, inhibition of FSH-induced follicular vascularization by PX-478, a small-molecule inhibitor that suppresses HIF-1α activity, blocked ovulation and triggered atresia in large follicles. On the other hand, PX-478 injection reduced oocyte quality via impairing the meiotic apparatus, showing a prominently defective spindle assembly and actin dynamics. Collectively, our findings unveiled a vascularization-independent effect of FSH on follicular growth, whereas follicular survival, ovulation, and oocyte development relies on FSH-mediated angiogenesis in the follicles.


Assuntos
Hormônio Foliculoestimulante/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Oócitos/crescimento & desenvolvimento , Folículo Ovariano/crescimento & desenvolvimento , Ovulação/metabolismo , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Feminino , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/fisiologia , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/metabolismo , Ovulação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
6.
Fertil Steril ; 113(2): 400-407.e1, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32106993

RESUMO

OBJECTIVE: To evaluate the impact of lymphoma aggressiveness on ovarian response during fertility preservation treatment. DESIGN: Retrospective cohort study. SETTING: University-affiliated tertiary hospital. PATIENT(S): Women with lymphoma who underwent ovarian stimulation for fertility preservation in the period from 2009 to 2018. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcome: the number of mature oocytes; secondary outcomes: the number of retrieved oocytes, estradiol level, and number of follicles >14 mm on the day of oocyte maturation trigger. RESULT(S): Patients with stage I-II lymphoid neoplasms (localized disease) were compared with those with stage III-IV lymphomas (advanced disease). Women with favorable levels of biochemical prognostic markers were also compared with those with unfavorable levels. Women with favorable levels of biochemical prognostic markers (n = 74) had a higher number of mature oocytes compared with patients with unfavorable serum levels (n = 67): 11 (7.8-16) versus 9 (5-11), respectively. The number of mature oocytes was similar between patients with localized (n = 75) and advanced (n = 66) lymphomas. Women with unfavorable combination of stage and biochemical factors had lower number of mature oocytes compared to patients with favorable combination: 8 (5-10) versus 11 (7-16), respectively. Multivariate logistic regression showed that favorable levels of biochemical markers as well as a combination of extent and biochemical parameters were statistically significantly associated with the result of over 10 mature oocytes. CONCLUSION(S): Highly-aggressive lymphoid neoplasms have a negative impact on ovarian function and response during fertility preservation treatment.


Assuntos
Fármacos para a Fertilidade Feminina/uso terapêutico , Preservação da Fertilidade , Linfoma/complicações , Recuperação de Oócitos , Ovário/efeitos dos fármacos , Indução da Ovulação , Ovulação/efeitos dos fármacos , Adolescente , Adulto , Biomarcadores/sangue , Estradiol/sangue , Feminino , Humanos , Linfoma/patologia , Linfoma/fisiopatologia , Estadiamento de Neoplasias , Ovário/metabolismo , Ovário/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
7.
Int. j. morphol ; 38(1): 165-175, Feb. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1056416

RESUMO

An alternative hyper-ovulator inducer to replace clomiphene citrate (CC) is needed as it is unsuitable for women with polycystic ovarian syndrome and is associated with low pregnancy rates. Anastrozole is an effective hyper-ovulator inducer, but has not been well researched. In order to determine the effectiveness of anastrozole as a hyper-ovulator inducer and to an extent compare it with CC in similar situations, this study ascertained the effects of these drugs on the expression of the focal adhesion proteins, paxillin and FAK, which are uterine receptivity markers in the surface luminal uterine epithelial cells of day 1 and day 6 pregnant Wistar rats. The results show that paxillin is localized in focal adhesions at the base of the uterine epithelial cells at day 1 of pregnancy whereas at day 6, paxillin disassembles from the basal focal adhesions and localizes and increases its expression apically. FAK is faintly expressed at the basal aspect of the uterine epithelial cells while moderately expressed at the cell-to-cell contact at day 1 in all groups from where it disassembles and relocates apically and becomes more intensely expressed at day 6 of pregnancy in untreated and anastrozole treated rats. Although paxillin is localized apically at day 6, its expression is significantly down-regulated with CC treatment suggesting its interference with the implantation process. These findings seem to suggest that anastrozole could favor implantation.


Para reemplazar el citrato de clomifeno (CC) es necesario un inductor de hiperovulación alternativo, ya que no es adecuado para mujeres con síndrome de ovario poliquístico y está asociado con tasas bajas de embarazo. El anastrozol es un inductor eficaz del hiper-ovulador, pero no se ha investigado adecuadamente. Con el fin de determinar la efectividad del anastrozol como inductor del hiper-ovulador y, en cierta medida, compararlo con CC en situaciones similares, este estudio determinó los efectos de estos fármacos en la expresión de las proteínas de adhesión focal, paxillin y FAK, uterinas marcadores de receptividad en la superficie luminal de células uterinas epiteliales, del día 1 y día 6 en ratas Wistar preñadas. Los resultados muestran que la paxilina se localiza en adherencias focales en la base de las células epiteliales uterinas en el día 1 del embarazo, mientras que en el día 6, la paxilina se desmonta de las adherencias focales basales y localiza y aumenta su expresión apicalmente. FAK se expresa débilmente en el aspecto basal de las células epiteliales uterinas, mientras que se expresa moderadamente en el contacto de célula a célula en el día 1 en todos los grupos, donde se separa y se reubica apicalmente y se expresa con mayor intensidad el día 6 de la preñez, en pacientes no tratados y tratados. ratas tratadas con anastrozol. Aunque la paxillina se localiza apicalmente en el día 6, su expresión está significativamente disminuida con el tratamiento con CC, lo que sugiere su interferencia con el proceso de implantación. Estos hallazgos sugieren que el anastrozol podría favorecer el proceso de implantación.


Assuntos
Animais , Feminino , Ratos , Útero/efeitos dos fármacos , Anastrozol/farmacologia , Ovulação/efeitos dos fármacos , Ratos Wistar , Adesões Focais/efeitos dos fármacos , Epitélio/efeitos dos fármacos , Proteína-Tirosina Quinases de Adesão Focal/efeitos dos fármacos , Paxilina/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Microscopia de Fluorescência
8.
Medicine (Baltimore) ; 99(4): e18383, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977842

RESUMO

OBJECTIVE: To compare the effects of letrozole and human menopausal gonadotropin (HMG) in the treatment of patients with polycystic ovary syndrome (PCOS) resistant to clomiphene citrate (CC). METHODS: A total of 96 clomiphene resistance polycystic ovary syndrome patients infertility were randomly divided into an LE group, and HMG group (n = 48). LE group orally received letrozole at 5.0 mg/d on the 3rd-5th days of menstrual cycle for 5 consecutive days, and 75 U/d HMG was given through intramuscular injection for 5 days starting from the third day of menstrual cycle in HMG group. Number of growing and mature follicles, serum E2 (pg/mL), serum P (ng/mL), endometrial thickness, occurrence of pregnancy and miscarriage were observed. RESULTS: There was no significant difference in the number of ovulation cycles between the 2 groups (53.6% vs 64.7%, P > .05). The number of mature follicular cycles in the HMG group was higher than that of the letrozole group (P < .01). There were no significant differences in the clinical pregnancy rate (22.9% vs 27.1%, P > .05) and abortion rate (6.2% vs 10.4%, P > .05). There was no significant difference in the endometrial thickness between the 2 groups on the day of HCG injection [(9.1 ±â€Š0.2) mm vs (10.7 ±â€Š1.6) mm, P > .05]; the serum estradiol (E2) was lower in the letrozole group. The incidence of ovarian cysts was lower than that of HMG group (P < .05). There was2 ovarian hyperstimulation syndrome in the letrozole group; the incidence of ovarian hyperstimulation syndrome in the HMG group was 12.5%. CONCLUSION: Letrozole-induced ovulation can obtain ovulation rate and pregnancy rate similar to gonadotropin, but reduce the risk associated with treatment. It can be used as an effective ovulation option for patients with polycystic ovary syndrome who are resistant to clomiphene.


Assuntos
Infertilidade Feminina/tratamento farmacológico , Letrozol/uso terapêutico , Menotropinas/uso terapêutico , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/tratamento farmacológico , Aborto Espontâneo/epidemiologia , Adulto , Clomifeno/farmacologia , Endométrio/efeitos dos fármacos , Estradiol/sangue , Feminino , Humanos , Cistos Ovarianos/induzido quimicamente , Síndrome de Hiperestimulação Ovariana/induzido quimicamente , Ovulação/efeitos dos fármacos , Gravidez , Adulto Jovem
9.
Fertil Steril ; 113(2): 417-425.e1, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31973903

RESUMO

OBJECTIVE: To compare live birth and multiple gestation in patients diagnosed with unexplained infertility undergoing intrauterine insemination after ovarian stimulation (OS-IUI) with oral medications versus gonadotropins. DESIGN: Systemic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Patients undergoing OS-IUI for treatment of unexplained infertility. INTERVENTION(S): Clomiphene, letrozole, or gonadotropins for OS-IUI. MAIN OUTCOME MEASURE(S): Live birth and multiple gestation. RESULT(S): Eight total trials were identified that met the inclusion criteria and comprised 2,989 patients undergoing 6,590 cycles. One study reported a significant increase in both live births and multiple gestations with the use of gonadotropins, two studies found an increased likelihood of live birth with the use of gonadotropins, and two studies found an increased risk of twins with gonadotropins. The relative risk of live birth in subjects receiving gonadotropins was 1.09. The relative risk of multiple gestation in subjects receiving gonadotropins was 1.06. Clinical pregnancy was higher in protocols with lax cancellation policies or higher gonadotropin doses, with subsequent increased relative risks of multiple gestations of 1.20 and 1.15, respectively. Singleton births per subject were similar between the two groups. The results did not change in per-protocol, per cycle, or fixed-effect model sensitivity analyses. CONCLUSION(S): For every birth gained with the use of gonadotropins, a similar increased risk of multiple gestation occurs. The randomized data do not support the use of gonadotropin for OS-IUI in women with unexplained infertility. CLINICAL TRIAL REGISTRATION NUMBER: Prospero CRD4201911998.


Assuntos
Clomifeno/administração & dosagem , Fármacos para a Fertilidade Feminina/administração & dosagem , Gonadotropinas/administração & dosagem , Infertilidade/terapia , Letrozol/administração & dosagem , Ovário/efeitos dos fármacos , Indução da Ovulação , Ovulação/efeitos dos fármacos , Administração Oral , Adolescente , Adulto , Clomifeno/efeitos adversos , Feminino , Fertilidade/efeitos dos fármacos , Fármacos para a Fertilidade Feminina/efeitos adversos , Gonadotropinas/efeitos adversos , Humanos , Infertilidade/diagnóstico , Infertilidade/etiologia , Infertilidade/fisiopatologia , Inseminação Artificial , Letrozol/efeitos adversos , Nascido Vivo , Masculino , Ovário/fisiopatologia , Indução da Ovulação/efeitos adversos , Gravidez , Taxa de Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
10.
Cancer Res ; 80(5): 1210-1218, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31932455

RESUMO

Repeated exposure to the acute proinflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2,045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted HRs between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than women in the 10th percentile (<294) [HR (95% confidence interval): 1.92 (1.60-2.30)]. Risk increased 14% per 5-year increase in LOC (60 cycles) [(1.10-1.17)]; this association remained after adjustment for LOC components: number of pregnancies and oral contraceptive use [1.08 (1.04-1.12)]. The association varied by histotype, with increased risk of serous [1.13 (1.09-1.17)], endometrioid [1.20 (1.10-1.32)], and clear cell [1.37 (1.18-1.58)], but not mucinous [0.99 (0.88-1.10), P-heterogeneity = 0.01] tumors. Heterogeneity across histotypes was reduced [P-heterogeneity = 0.15] with adjustment for LOC components [1.08 serous, 1.11 endometrioid, 1.26 clear cell, 0.94 mucinous]. Although the 10-year absolute risk of ovarian cancer is small, it roughly doubles as the number of LOC rises from approximately 300 to 500. The consistency and linearity of effects strongly support the hypothesis that each ovulation leads to small increases in the risk of most ovarian cancers, a risk that cumulates through life, suggesting this as an important area for identifying intervention strategies. SIGNIFICANCE: Although ovarian cancer is rare, risk of most ovarian cancers doubles as the number of lifetime ovulatory cycles increases from approximately 300 to 500. Thus, identifying an important area for cancer prevention research.


Assuntos
Neoplasias Ovarianas/epidemiologia , Ovário/imunologia , Ovulação/imunologia , Idoso , Anticoncepcionais/administração & dosagem , Tubas Uterinas/imunologia , Tubas Uterinas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/prevenção & controle , Ovário/patologia , Ovulação/efeitos dos fármacos , Modelos de Riscos Proporcionais , Estudos Prospectivos , História Reprodutiva , Medição de Risco , Fatores de Risco
11.
Gen Comp Endocrinol ; 287: 113351, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31805285

RESUMO

A relaxin-like gonad-stimulating peptide (RGP), comprising two peptide chains (A- and B-chains) linked by two interchain bonds and one intrachain disulfide bond, acts as a gonadotropin in starfish. RGP orthologs have been identified in several starfish species, including Patiria pectinifera (PpeRGP), Asterias rubens (AruRGP) and Aphelasterias japonica (AjaRGP). To analyze species-specificity, this study examined the effects on oocyte maturation and ovulation in ovaries of A. rubens and A. japonica of nine RGP derivatives comprising different combinations of A- and B-chains from the three species. All nine RGP derivatives induced spawning in A. rubens and A. japonica ovaries. However, AruRGP, AjaRGP and their chimeric derivatives were more potent than peptides containing the A- or B-chain of PpeRGP. Three-dimensional models of the structures of the RGP derivatives revealed that residues in the B-chains, such as AspB6, MetB10 and PheB13 in PpeRGP and GluB7, MetB11, and TyrB14 in AruRGP and AjaRGP, respectively, are likely to be involved in receptor binding. Conversely, it is likely that ArgA18 in the A-chain of AruRGP and AjaRGP impairs binding of these peptides to the PpeRGP receptor in P. pectinifera. In conclusion, this study provides new insights into the structural basis of RGP bioactivity and RGP receptor activation in starfish.


Assuntos
Asterias/fisiologia , Hormônios de Invertebrado/farmacologia , Neuropeptídeos/farmacologia , Oogênese/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Hormônios Peptídicos/farmacologia , Animais , Asterias/efeitos dos fármacos , Feminino , Hormônios de Invertebrado/química , Neuropeptídeos/química , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Ovário/efeitos dos fármacos , Ovário/metabolismo , Hormônios Peptídicos/química , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/farmacologia , Relaxina/química , Estrelas-do-Mar/efeitos dos fármacos , Estrelas-do-Mar/fisiologia
12.
Life Sci ; 241: 117100, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31783052

RESUMO

AIMS: The present study aims to define maturation, yield, health, and ease of collection of murine immature oocytes recovered using the conventional method or from mice treated with cilostazol. MAIN METHODS: The conventional method included the superovulation of mice and the recovery of germinal vesicle (GV) or metaphase (MI) oocytes from preovulatory follicles. The cilostazol method included the oral treatment of superovulated mice with 7.5 mg cilostazol once or twice to result in the ovulation of MI or GV oocytes, respectively. KEY FINDINGS: The cilostazol method resulted in >95% of GV or MI oocytes with a diameter range of 60-90 µm or 50.1-70 µm in comparison to <60.0% of GV or MI oocytes resulting from the conventional method, respectively (P < 0.0001). The cilostazol method resulted in GV oocytes having higher levels of co-occurrence of peripheral cortical granules (CG) and chromatin configuration of surrounded nucleolus and MI oocytes having higher levels of co-occurrence of normally organized spindles/chromosomes and peripheral CG with free domains than did the conventional method (P < 0.001). The cilostazol method was more time and labor efficient and resulted in higher oocyte yields of normal morphology than did the conventional method (P < 0.01). SIGNIFICANCE: The presented method provides not only oocytes with uniform size and synchronized developmental maturation but also a technique of oocyte collection that is efficient and resourceful. It is possible that not all immature oocytes resulting from the conventional method are from preovulatory follicles nor have been developed adequately and consequently ovulated as opposed to the presented method.


Assuntos
Cilostazol/farmacologia , Recuperação de Oócitos/métodos , Oócitos/citologia , Oócitos/fisiologia , Inibidores da Fosfodiesterase 3/farmacologia , Animais , Nucléolo Celular , Núcleo Celular , Cromatina/ultraestrutura , Feminino , Técnicas de Maturação in Vitro de Oócitos/métodos , Metáfase , Camundongos , Ovulação/efeitos dos fármacos , Superovulação/efeitos dos fármacos
13.
J Reprod Dev ; 66(1): 93-96, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-31735733

RESUMO

To prevent twin pregnancies in cattle, a simple transvaginal device can be used for follicular drainage. This study examines embryo survival following follicular drainage of the smaller pre-ovulatory follicle at timed artificial insemination (AI) in cows with a pre-ovulatory follicle in each ovary. The study groups established were a control group of 289 monovular cows, a non-drainage group of 114 bi-ovular cows and a follicular drainage group of 113 bi-ovular cows. All cows undergoing drainage developed a corpus luteum (CL) in the drained ovary. Pregnancy loss was recorded 56 days post-AI in 19.5% of the 149 cows that became pregnant. Pregnancy loss in the drainage group cows not suffering heat stress (3.8%) was significantly lower (P < 0.05) than in control non-heat stressed cows (20.9%) and heat-stressed non-drainage group cows (25%). Results indicate that CL induction by follicular drainage for twin pregnancy prevention may reduce the incidence of pregnancy loss.


Assuntos
Indústria de Laticínios , Drenagem , Inseminação Artificial/veterinária , Folículo Ovariano/fisiologia , Animais , Bovinos , Corpo Lúteo/efeitos dos fármacos , Corpo Lúteo/fisiologia , Feminino , Fertilidade/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/farmacologia , Folículo Ovariano/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Gravidez , Gravidez Múltipla
14.
Am J Obstet Gynecol ; 222(5): 476.e1-476.e11, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31738897

RESUMO

BACKGROUND: Studies investigating the effects of pain-relieving medication use on conceiving a pregnancy have shown conflicting results. Furthermore, no previous study has examined medication use around ovulation or implantation and the associations with the probability of conception, fecundability. OBJECTIVE: The objective of the study was to explore the association between fecundability and analgesic use in 3 different menstrual cycle windows (preovulation, periovulation, and implantation) as well as across the entire menstrual cycle. STUDY DESIGN: We analyzed data from a prospective cohort study of women between 30 and 44 years of age who were trying to conceive naturally from 2008 through 2015. Using daily diaries, medication usage was classified as acetaminophen, aspirin, or nonaspirin nonsteroidal antiinflammatory drug during 4 time periods of interest (preovulatory, periovulatory, and implantation) as well as the overall nonmenstrual bleeding days of the cycle. Menstrual cycles during the prospective attempt to become pregnant were enumerated using daily diary menstrual bleeding information. Conception was defined as a positive home pregnancy test. Discrete time fecundability models were used to estimate the fecundability ratio and 95% confidence interval in each of the 4 time windows of interest and for each pain reliever (aspirin use, nonaspirin nonsteroidal antiinflammatory drug use, acetaminophen) compared with no medication use after adjustment for several covariates including age, race, education, body mass index, alcohol and caffeine use, frequency of intercourse, and a history of migraines or uterine fibroids. RESULTS: Medication use was infrequent in the 858 women and 2366 cycles in this analysis. Use of nonaspirin nonsteroidal antiinflammatory drugs or acetaminophen was not associated with fecundability in any of the time windows of interest. Although the sample size was small, aspirin use during the implantation window was associated with increased fecundability (adjusted fecundability ratio [confidence interval]: 2.05 [1.23-3.41]). This association remained when limiting the analysis to cycles with minimal missing data or when adjusting for gravidity. None of the other medications were associated with fecundability. CONCLUSION: Aspirin use around implantation was associated with increased fecundability. These results expand previous literature to suggest the following: (1) implantation may be an important target for the effects of aspirin on conception and (2) aspirin may be beneficial, regardless of pregnancy loss history. These observations should be tested with a clinical trial.


Assuntos
Acetaminofen/administração & dosagem , Analgésicos/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Implantação do Embrião/efeitos dos fármacos , Fertilidade/efeitos dos fármacos , Fertilização/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Acetaminofen/uso terapêutico , Adulto , Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Feminino , Humanos , Ciclo Menstrual/efeitos dos fármacos , Dor/tratamento farmacológico , Gravidez , Estudos Prospectivos
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.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31650182

RESUMO

CONTEXT: Elagolix is an oral gonadotropin-releasing hormone (GnRH) antagonist recently approved for the treatment of endometriosis-associated pain and being developed for heavy menstrual bleeding associated with uterine fibroids. OBJECTIVE: The objective was to evaluate the effects of elagolix on ovulation and ovarian sex hormones. DESIGN AND SETTING: This was a randomized, open-label, multicenter study. PARTICIPANTS: Participants were healthy ovulatory women aged 18 to 40 years. INTERVENTIONS: Elagolix was administered orally for 3 continuous 28-day dosing intervals at 100 to 200 mg once daily (QD), 100 to 300 mg twice daily (BID), and 300 mg BID plus estradiol/norethindrone acetate (E2/NETA) 1/0.5 mg QD. MAIN OUTCOME MEASURES: The main outcomes measures were ovulation rates measured by transvaginal ultrasound, progesterone concentrations, and hormone suppression. RESULTS: Elagolix suppressed ovulation in a dose-dependent manner. The percentage of women who ovulated was highest at 100 mg QD (78%), intermediate at 150 and 200 mg QD and 100 mg BID (47%-57%), and lowest at 200 and 300 mg BID (32% and 27%, respectively). Addition of E2/NETA to elagolix 300 mg BID further suppressed the ovulation rate to 10%. Elagolix also suppressed luteinizing hormone and follicle stimulating hormone in a dose-dependent manner, leading to dose-dependent suppression of estradiol and progesterone. Elagolix had no effect on serum biomarker of ovarian reserve, and reduced endometrial thickness compared to the screening cycle. CONCLUSION: Women being treated with elagolix may ovulate and should use effective methods of contraception. The rate of ovulation was lowest with elagolix 300 mg BID plus E2/NETA 1/0.5 mg QD.


Assuntos
Endométrio/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hidrocarbonetos Fluorados/administração & dosagem , Menorragia/tratamento farmacológico , Ovulação/efeitos dos fármacos , Pirimidinas/administração & dosagem , Adolescente , Adulto , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Antagonistas de Hormônios/administração & dosagem , Antagonistas de Hormônios/farmacologia , Humanos , Hidrocarbonetos Fluorados/farmacologia , Prognóstico , Pirimidinas/farmacologia , Fatores de Tempo , Adulto Jovem
17.
Trop Anim Health Prod ; 52(2): 503-509, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31392554

RESUMO

Twenty-eight pluriparous and non-lactating Santa Inês sheep were synchronized with vaginal sponge and an intramuscular (IM) injection of 37.5 µg of cloprostenol on random days of the estrous cycle (D0); day 6 (D6), at 7:00 am, the devices were removed, and after 24 h (D7), GnRH analog (25 µg of lecirelin) was administrated. Fixed-time artificial insemination (FTAI) with cervical traction by the transcervical route was performed 52 to 58 h after sponge removal. Doppler velocimetry of both uterine arteries was performed on D0, D2, D4, and the morning of D6 (every 48 h), and then every 12 h from D6 to D8 (7:00 a.m. and 7:00 p.m.). We analyzed the peak systolic velocity (PSV), end-diastolic velocity (EVD), time-averaged maximum and mean velocity (TAMAX, TAMEAN), pulsatility index (PI), resistance index (RI), systolic/diastolic ratio (S/D), arterial diameter (AD), and blood flow volume (BFV), with the objective of evaluating the hemodynamic behavior of blood flow velocity parameters of the uterine artery during a short-term progesterone synchronization protocol in ewes. With respect to phases, we noted increases in the means of TAMAX and TAMEAN and decreases of EDV, PI, and RI (P < 0.05). S/D, EDV, TAMEAN, PI, RI, SD, AD, and BFV showed differences between the time of progesterone insertion and the estimated time of ovulation (which was considered the last evaluation) (P < 0.05). The PI and RI values were different when comparing the times of insertion and withdrawal of the progesterone device (PI 2.53-1.54 and RI 0.76-0.68) (P < 0.05). The PI was different with respect to side (P < 0.001), but no side effect was seen in the RI. In conclusion, the two uterine arteries behave differently under the effect of progesterone (intravaginal sponges) and the effect of estradiol during the follicular phase, and estrous phase was responsible for increasing uterine blood flow.


Assuntos
Cloprostenol/farmacologia , Sincronização do Estro , Hemodinâmica , Luteolíticos/farmacologia , Carneiro Doméstico/fisiologia , Útero/irrigação sanguínea , Animais , Feminino , Inseminação Artificial/veterinária , Oligopeptídeos/administração & dosagem , Ovulação/efeitos dos fármacos , Progesterona , Artéria Uterina
18.
Theriogenology ; 142: 276-283, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31708195

RESUMO

The peroxisome proliferator-activated receptor gamma (PPARG, also called NR1C3) is a nuclear receptor of the peroxisome proliferator-activated receptor family (PPAR). PPARs are involved in the regulation of apoptosis, cell cycle, estradiol and progesterone synthesis, and metabolism. However, the role of PPARs and their regulation during follicular development and ovulation in monovular species remain poorly understood. In this study, a well-established intrafollicular injection model was used to investigate if the PPARG participates in the regulation of dominant follicle development and ovulation in cattle. Findings from this study revealed that the relative mRNA abundance of PPARG was similar between dominant and subordinate follicles around follicle deviation, decreased after the LH surge, and increased before ovulation. In addition, a quadratic correlation was found between PPARG mRNA levels in granulosa cells and progesterone concentration in the follicular fluid. Intrafollicular injection of 50 µM Troglitazone (TGZ; a PPARG agonist) inhibited follicular growth and decreased CYP19A1 mRNA abundance in granulosa cells. These findings indicate that PPARG is involved in the regulation of steroidogenesis, follicle growth and ovulation in cattle.


Assuntos
Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/fisiologia , PPAR gama/agonistas , Troglitazona/farmacologia , Animais , Bovinos , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Feminino , Expressão Gênica/efeitos dos fármacos , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/fisiologia , Oogênese/efeitos dos fármacos , Oogênese/genética , Ovulação/efeitos dos fármacos , Ovulação/genética , PPAR gama/genética , PPAR gama/metabolismo
19.
J Dairy Sci ; 103(3): 2743-2755, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31882220

RESUMO

Our objectives were to test the efficacy of intravaginal (IVG) administration of PGF2α to induce corpus luteum (CL) regression, compare circulating progesterone (P4) profiles in cows receiving IVG versus intramuscular (IM) treatment with PGF2α, and evaluate reproductive outcomes. Lactating Holstein cows were synchronized using a Double-Ovsynch protocol [GnRH, 7 d later PGF2α, 3 d later GnRH, 7 d later GnRH, 7 d later PGF2α, 1 d later PGF2α, 32 h later GnRH, 16 to 20 h timed artificial insemination (TAI)] to receive TAI at 67 ± 3 d in milk. Seven days after the first GnRH treatment (time 0), cows with at least 1 visible CL ≥15 mm were blocked by parity and randomly assigned to a treatment that consisted of IM injection (IM-PGF; n = 201) or IVG instillation (IVG-PGF; n = 201) of PGF2α. Cows in IM-PGF received a single 25-mg dose of PGF2α (dinoprost tromethamine) intramuscularly. Cows in IVG-PGF received two 25-mg doses of PGF2α 12 h apart delivered through a catheter in the cranial portion of the vagina. Blood samples were collected at 0, 12, 48, and 72 h after treatment. Ovulation to the first GnRH of Double-Ovsynch was determined through transrectal ultrasonography. Only cows with P4 ≥1 ng/mL (functional CL) at time 0 (IM-PGF = 169; IVG-PGF = 179) were included in the analyses. Binary and quantitative data were analyzed by logistic regression and ANOVA with repeated measures, respectively. Results are presented as least squares means. Concentrations of P4 and the proportion of cows with a new CL at time 0 did not differ. Overall, the proportion of cows with CL regression using 1 ng of P4/mL (IM-PGF = 89.0%; IVG-PGF = 86.7%) or 0.5 ng of P4/mL (IM-PGF = 82.2%; IVG-PGF = 82.1%) as the cutoff did not differ. Concentrations of P4 were affected by treatment, time, and treatment × time interaction. Cows in IVG-PGF had greater mean P4 at 12 h than cows in IM-PGF. Mean P4 did not differ at 48 or 72 h after treatment. The proportion of cows with estrus recorded within 3 d of treatment (IM-PGF = 45.4%; IVG-PGF = 48.9%), ovulation risk after treatment (IM-PGF = 88.5%; IVG-PGF = 85.1%), and pregnancies per artificial insemination after TAI (IM-PGF = 51.5%; IVG-PGF = 57.8%) did not differ. We concluded that 2 IVG doses of 25 mg of PGF2α 12 h apart were as effective as a single 25-mg IM dose of PGF2α for inducing luteal regression in lactating dairy cattle.


Assuntos
Bovinos/fisiologia , Dinoprosta/análogos & derivados , Luteólise/efeitos dos fármacos , Ocitócicos/administração & dosagem , Reprodução , Administração Intravaginal , Animais , Dinoprosta/administração & dosagem , Estro/efeitos dos fármacos , Sincronização do Estro , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Injeções Intramusculares/veterinária , Inseminação Artificial/veterinária , Lactação , Ovulação/efeitos dos fármacos , Paridade , Gravidez , Progesterona/sangue , Distribuição Aleatória
20.
Gen Comp Endocrinol ; 288: 113373, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31874135

RESUMO

Using medaka, we found that in vitro follicle ovulation, but not germinal vesicle breakdown, was inhibited by three gap junction blockers, carbenoxolone, mefloquine, and flufenamic acid. The blockers specifically inhibited follicular expression of matrix metalloproteinase-15 mRNA and the protein (mmp15/Mmp15), a protease indispensable for medaka ovulation, indicating that gap junctional communication may be required for successful ovulation and mmp15/Mmp15 expression. Further experiments using carbenoxolone as the representative of the gap junction blockers showed that expression of nuclear progestin receptor (Pgr), a transcription factor required for mmp15 expression, was not affected by carbenoxolone treatment, but the formation of phosphorylated Pgr was considerably suppressed. Carbenoxolone treatment caused a decrease in the Pgr binding to the promoter region of mmp15. mRNA expression of cyclin-dependent protein kinase-9 (cdk9) and cyclin I (ccni), whose translation products are demonstrated to be involved in Pgr phosphorylation in the medaka ovulating follicles, was suppressed by carbenoxolone treatment. Transcripts of connexin 34.5 (cx34.5) and connexin 35.4 (cx35.4) were dominantly expressed in the follicle cells of ovulating follicles. The results indicate that gap junctional communication plays an important role in medaka ovulation.


Assuntos
Disruptores Endócrinos/farmacologia , Junções Comunicantes/efeitos dos fármacos , Hormônio Luteinizante/farmacologia , Metaloproteinase 15 da Matriz/genética , Oryzias/fisiologia , Ovulação/efeitos dos fármacos , Animais , Carbenoxolona/farmacologia , Feminino , Ácido Flufenâmico/farmacologia , Junções Comunicantes/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Metaloproteinase 15 da Matriz/efeitos dos fármacos , Metaloproteinase 15 da Matriz/metabolismo , Mefloquina/farmacologia , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/metabolismo , Ovulação/genética , Ativação Transcricional/efeitos dos fármacos
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