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1.
BMC Med Genet ; 21(1): 11, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31918667

RESUMO

BACKGROUND: To investigated the role of miR-19b-3p in regulating bone marrow mesenchymal stem cell (BMSC) proliferation and osteoblast differentiation. METHODS: The expression of miR-19b-3p and lncRNA H19 were measured in postmenopausal osteoporosis patients and BMP-22 induced BMSCs using qRT-PCR. MiR-19b-3p mimic or inhibitor was transfected into BMP-2 induced BMSCs. Cell proliferation was measured by BrdU method. Protein expression of RUNX2 and COL1A1 were measured by western blot. PcDNA3.1-lncRNA H19 with or without miR-19b-3p mimic was transfected into BMP-2 induced BMSCs. RESULTS: The expression of miR-19b-3p was significantly up-regulated in postmenopausal osteoporosis patients and BMP-2 induced BMSCs. MiR-19b-3p overexpression dramatically elevated, while miR-19b-3p inhibition decreased cell proliferation of BMSCs. Additionally, protein expression levels of RUNX2 and COL1A1, as well as ALP activity were significantly promoted by miR-19b-3p mimic transfection and inhibited by miR-19b-3p inhibitor transfection. LncRNA H19 was obviously down-regulated in postmenopausal osteoporosis patients. H19 overexpression significantly decreased cell proliferation and differentiation by down-regulating miR-19b-3p. Moreover, the expression of miR-19b-3p was inhibited, while H19 elvated in 17ß-estradiol (E2) treated BMSCs in a dose-dependent manner. CONCLUSION: These data were the first to reveal the critical role of H19/miR-19b-3p in postmenopausal osteoporosis, and provided a new therapeutic target for OP.


Assuntos
MicroRNAs/genética , Osteogênese/genética , Osteoporose Pós-Menopausa/genética , RNA Longo não Codificante/genética , Proteína Morfogenética Óssea 2/genética , Diferenciação Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Colágeno Tipo I/genética , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Estradiol/administração & dosagem , Feminino , Humanos , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Osteoblastos/metabolismo , Osteoporose Pós-Menopausa/patologia
2.
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
3.
Gen Comp Endocrinol ; 285: 113272, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31525376

RESUMO

It is widely known that reproduction in vertebrates is regulated by the hypothalamus-pituitary-gonadal (HPG) axis. Although the mechanism of the HPG axis has been well documented in mammals, it cannot be always applied to that in non-mammalian species, which is a great disadvantage in understanding reproduction of vertebrates in general. Recently, transgenic and genome editing tools have rapidly been developed in small teleosts, and thus these species are expected to be useful for the understanding of general mechanism of reproduction in vertebrates. One of the major sex steroid hormones in female vertebrates 17ß-Estradiol (E2) plays crucial roles in the formation of sexual dimorphism and the HPG axis regulation. In spite of the importance of E2 in reproductive regulation, only a few studies have analyzed blood E2 levels in small teleosts that are easily amenable to genetic manipulation. In the present study, we analyzed blood E2 concentration in medaka and demonstrated that female medaka show diurnal changes in blood E2 concentration. We then examined the best method for manipulating the circulating E2. First, we found that ovariectomy (OVX) drastically removes endogenous E2 in a day in female medaka. We examined different methods for E2 administration and revealed that feeding administration of E2-containing food is the most convenient and physiological method for mimicking the diurnal E2 changes of female medaka. On the other hand, the medaka exposed to E2 containing water showed high blood E2 concentrations, which exceeds those of environmental water, suggesting that E2 may cause bioconcentration.


Assuntos
Estradiol/sangue , Oryzias/sangue , Testes Sorológicos/métodos , Animais , Estradiol/administração & dosagem , Feminino , Masculino , Oryzias/genética , Ovariectomia , Fatores de Tempo
4.
Braz J Med Biol Res ; 53(1): e8659, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31859912

RESUMO

Eosinophils are abundant in the reproductive tract, contributing to the remodeling and successful implantation of the embryo. However, the mechanisms by which eosinophils migrate into the uterus and their relationship to edema are still not entirely clear, since there are a variety of chemotactic factors that can cause migration of these cells. Therefore, to evaluate the role of CCR3 in eosinophil migration, ovariectomized C57BL/6 mice were treated with CCR3 antagonist SB 328437 and 17ß-estradiol. The hypothesis that the CCR3 receptor plays an important role in eosinophil migration to the mouse uterus was confirmed, because we observed reduction in eosinophil peroxidase activity in these antagonist-treated uteruses. The antagonist also influenced uterine hypertrophy, inhibiting edema formation. Finally, histological analysis of the orcein-stained uteruses showed that the antagonist reduced eosinophil migration together with edema. These data showed that the CCR3 receptor is an important target for studies that seek to clarify the functions of these cells in uterine physiology.


Assuntos
Movimento Celular/efeitos dos fármacos , Eosinófilos/efeitos dos fármacos , Estradiol/administração & dosagem , Estrogênios/administração & dosagem , Receptores CCR3/antagonistas & inibidores , Útero/citologia , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Ovariectomia
5.
Nat Commun ; 10(1): 4830, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645570

RESUMO

Central nervous system (CNS) injuries persist for years, and currently there are no therapeutics that can address the complex injury cascade that develops over this time-scale. 17ß-estradiol (E2) has broad tropism within the CNS, targeting and inducing beneficial phenotypic changes in myriad cells following injury. To address the unmet need for vastly prolonged E2 release, we report first-generation poly(pro-E2) biomaterial scaffolds that release E2 at nanomolar concentrations over the course of 1-10 years via slow hydrolysis in vitro. As a result of their finely tuned properties, these scaffolds demonstrate the ability to promote and guide neurite extension ex vivo and protect neurons from oxidative stress in vitro. The design and testing of these materials reported herein demonstrate the first step towards next-generation implantable biomaterials with prolonged release and excellent regenerative potential.


Assuntos
Astrócitos/efeitos dos fármacos , Materiais Biocompatíveis , Estradiol/farmacologia , Estrogênios/farmacologia , Gânglios Espinais/efeitos dos fármacos , Crescimento Neuronal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Fármacos do Sistema Nervoso Central/administração & dosagem , Fármacos do Sistema Nervoso Central/química , Fármacos do Sistema Nervoso Central/farmacologia , Implantes de Medicamento/química , Estradiol/administração & dosagem , Estradiol/química , Estrogênios/administração & dosagem , Estrogênios/química , Técnicas In Vitro , Macrófagos , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Polímeros/química , Cultura Primária de Células , Pró-Fármacos/administração & dosagem , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Ratos , Medula Espinal/citologia
6.
J Nutr Sci Vitaminol (Tokyo) ; 65(4): 357-361, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474686

RESUMO

Autophagy is a major intracellular proteolytic process that contributes to the maintenance of protein homeostasis. Recent studies reported the induction of autophagy in the uterus and proximal tibias of ovariectomized (OVX) rodents, which was blocked by the injection of ovarian hormones. However, whether OVX and ovarian hormone treatment can regulate autophagy in the liver has not been clarified. Recently, it was revealed that autophagy is closely involved in hepatic lipid metabolism. The purpose of this study was to investigate the influence of OVX on autophagy in the rat liver as a first step to clarify the relationship between hepatic fat accumulation and the change in autophagy caused by OVX. We found that hepatic autophagy tended to be lower in OVX rats than in sham-operated rats. In addition, hepatic autophagy in OVX rats was induced by short-term exposure to ovarian hormones, especially progesterone. This study suggests that autophagy in the rat liver is suppressed by OVX and activated by progesterone. However, the autophagy-promoting effect of ß-estradiol was not clarified.


Assuntos
Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Estradiol/administração & dosagem , Fígado/fisiologia , Ovariectomia , Progesterona/administração & dosagem , Animais , Feminino , Metabolismo dos Lipídeos/fisiologia , Ratos , Ratos Sprague-Dawley
7.
J Anim Sci ; 97(11): 4371-4385, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31541251

RESUMO

Predominately Angus steers (n = 24; initial BW = 435 ± 28.3 kg) were used to evaluate non-coated (NC) and coated implants (CI) containing equal amounts of trenbolone acetate (TBA; 200 mg) and estradiol benzoate (EB; 28 mg) in finishing steers on sera metabolite responses, gene expression, and immunohistochemical analyses of the Longissimus muscle (LM). Performance data were analyzed as a randomized complete block design, and all other data were analyzed as repeated measures for a completely randomized design. Treatments were no implant (NI), NC (Synovex-PLUS; Zoetis, Parsippany, NJ), and CI (Synovex-One Feedlot) implant. There were 2 pen replicates per treatment (n = 4 steers/pen). LM biopsies, blood, and BW were collected before feeding on days 0, 14, 28, 56, 84, 112, and 133, with final BW being captured on day 140. Genes of interest were determined by RT-qPCR using two housekeeping genes. Sera was analyzed for estradiol-17ß (E2),17ß-trenbolone (TbOH), insulin-like growth factor 1 (IGF-I), NEFA, and urea-N (SUN). An α of 0.10 determined significance for performance and sera data; α of 0.05 was used for gene and histology data. No performance differences (P ≥ 0.10) were detected. An implant × day interaction (P ≤ 0.10) for E2, IGF-I, and SUN was detected; implants elevated (P ≤ 0.10) E2, 17ß-TbOH, and IGF-I; and decreased SUN across day of the study, meaning sera metabolites are not altered with time on feed. An implant × day interaction was detected for myogenic factor 5 (MYF-5) positive cells and proportions of MHCIIX. In LM, CI had greater (P < 0.10) IGF-I in LM over NI. CI increased (P < 0.05) G protein-coupled estrogen receptor 1 (GPER1) expression, as well as, GPER1 semi-quantitative scores over NI and NC. An implant × day interaction (P ≤ 0.05) for estrogen and androgen receptor-positive nuclei was detected; implants had increased (P ≤ 0.05) estrogen and androgen receptor-positive nuclei compared to NI. CIs increase genes associated with muscle tissue growth.


Assuntos
Anabolizantes/administração & dosagem , Bovinos/fisiologia , Estradiol/análogos & derivados , Esteroides/administração & dosagem , Acetato de Trembolona/administração & dosagem , Anabolizantes/sangue , Ração Animal , Animais , Bovinos/sangue , Dieta/veterinária , Implantes de Medicamento/administração & dosagem , Ingestão de Alimentos , Estradiol/administração & dosagem , Estradiol/sangue , Imuno-Histoquímica/veterinária , Fator de Crescimento Insulin-Like I/análise , Masculino , Músculo Esquelético/metabolismo , Distribuição Aleatória , Carne Vermelha/análise , Acetato de Trembolona/sangue
9.
Emerg Microbes Infect ; 8(1): 1146-1156, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31364945

RESUMO

Estradiol, a major female steroid produced during pregnancy, has been reported to protect ovariectomized animals against H1N1 influenza infections via its anti-inflammatory effects. However, it remains unclear why pregnant women with high gestational estradiol levels are highly susceptible to influenza infections. This study was aimed to investigate the effects of pregnancy level of estradiol on female immunity against H5N1 infection in Balb/c mice. A sex-dependent susceptibility to H5N1 infection (higher morbidity and higher mortality) was observed in both pregnant and non-pregnant female mice as compared to male mice. Subcutaneous implantation of estradiol pellets increased serum estradiol concentrations of non-pregnant female mice to the pregnancy level. These mice were protected from H5N1 infection through downregulation of pulmonary pro-inflammatory cytokines. However, the production of virus-specific antibodies after infection was significantly delayed in estradiol-implanted mice when compared to placebos. Virus-specific IgG-secreting and IL-4-secreting cells were also reduced in estradiol-implanted mice. Similarly, lower antibody titers to seasonal vaccine antigens were found in pregnant women as compared to non-pregnant females without hormone usage. Our results indicate that estradiol levels equivalent to those found during pregnancy have divergent effects on female immunity against influenza, highlighting the importance of vaccination during pregnancy to prevent severe influenza infections.


Assuntos
Anti-Inflamatórios/sangue , Resistência à Doença , Estradiol/sangue , Imunidade Humoral , Virus da Influenza A Subtipo H5N1/imunologia , Infecções por Orthomyxoviridae/imunologia , Complicações Infecciosas na Gravidez/imunologia , Animais , Anti-Inflamatórios/administração & dosagem , Modelos Animais de Doenças , Estradiol/administração & dosagem , Feminino , Imunoglobulina G/sangue , Pulmão/patologia , Masculino , Camundongos Endogâmicos BALB C , Gravidez , Fatores Sexuais
10.
Expert Rev Clin Pharmacol ; 12(8): 729-739, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31282768

RESUMO

Introduction: Many women seek treatment to alleviate menopausal vasomotor symptoms (VMS). Numerous women use combination compounded hormone therapy (CHT) to achieve the benefits of estrogen/progesterone for endometrial protection. TX-001HR is a combination of bioidentical 17ß-estradiol (E2) and progesterone (P4) in a single capsule designed for continuous daily use to treat moderate to severe VMS. Areas covered: This drug profile describes the efficacy and safety of 4 doses of this E2/P4 (mg/mg: 1/100, 0.5/100, 0.5/50, 0.25/50) for treating moderate to severe VMS in menopausal woman with a uterus. Expert opinion: In REPLENISH (NCT01942668), the two highest doses of TX-001HR significantly reduced VMS frequency and severity at 4 and 12 weeks versus placebo (co-primary endpoints); all doses met the primary endpoint of endometrial safety. Rates of amenorrhea were high and improved over time; the Menopause Quality of Life and Medical Outcomes Study-Sleep instruments improved with E2/P4. TX-001HR was well tolerated and had no clinically significant impact on vital signs, metabolic or coagulation parameters, or breast safety. The combination bioidentical E2/P4 capsule (1 mg/100 mg dose was FDA-approved as Bijuva in October 2018) may provide a safe, effective, rigorously studied alternative for women with a uterus who prefer CHT for relief of VMS.


Assuntos
Estradiol/administração & dosagem , Menopausa , Progesterona/administração & dosagem , Qualidade de Vida , Administração Oral , Cápsulas , Relação Dose-Resposta a Droga , Estradiol/efeitos adversos , Estradiol/farmacologia , Feminino , Fogachos/tratamento farmacológico , Humanos , Progesterona/efeitos adversos , Progesterona/farmacologia , Índice de Gravidade de Doença , Sudorese/efeitos dos fármacos
11.
Reprod Biol ; 19(2): 210-217, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31262644

RESUMO

Clinical outcomes of fresh embryo transfer in non-hCG triggered in vitro maturation (IVM) cycles are inferior compared to vitrified-warmed embryo transfer. This is a prospective observational pilot study in a consecutive cohort of 31 polycystic ovary syndrome (PCOS) patients and 37 normo-ovulatory egg donors who underwent IVM without fresh embryo transfer between July 2009 and June 2014. All subjects received 150 IU of highly purified menotropin (HP-hMG) daily for three days. On cycle day 6, all patients started transdermal oestradiol (E2) at a daily dose of 9 mg. There was no human chorionic gonadotropin (hCG) trigger before oocyte retrieval (OR). Vaginal micronized progesterone was commenced on the evening after OR, at a daily dose of 600 mg. Additional luteal phase support (LPS) was administered as follows: Group A: no additional LPS; Group B: 1500 IU of hCG administered 4 h after OR and Group C: 5000 IU of hCG administered 4 h after OR + an additional injection of 5000 IU of hCG 1 day before endometrial biopsy. Endometrial biopsy for histology and immunohistochemistry (IHC) was performed on day 5 or 6 after OR. Instead of being downregulated, both PR-B and ERα in endometrial glands and stroma were moderately to strongly expressed in all three protocols, suggesting that the mid-luteal histological signature of endometrial receptivity is deficient in a non-hCG-triggered IVM cycle. Poor clinical outcomes after fresh embryo transfer following IVM are probably related to inappropriate endometrial development which may be linked to the short follicular phase of IVM cycles.


Assuntos
Gonadotropina Coriônica/farmacologia , Endométrio/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Síndrome do Ovário Policístico/metabolismo , Receptores de Esteroides/metabolismo , Adulto , Gonadotropina Coriônica/administração & dosagem , Estudos de Coortes , Estradiol/administração & dosagem , Estradiol/farmacologia , Feminino , Humanos , Técnicas de Maturação in Vitro de Oócitos , Projetos Piloto , Progesterona/administração & dosagem , Progesterona/farmacologia , Estudos Prospectivos , Receptores de Esteroides/genética , Adulto Jovem
12.
Ren Fail ; 41(1): 507-520, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31216906

RESUMO

Menopause is an important physiological event associated with structural and functional changes in the kidneys. An animal model of bilateral ovariectomy was used to study the effects of estrogen depletion, replacement and antiestrogen on renal structure and endocrine function. Sixty female rats were divided into six groups; group I was the control group, the remaining five groups underwent ovariectomy: group II received no treatment. The other groups received estradiol in group III, tamoxifen in group IV, estradiol followed by tamoxifen in group V and tamoxifen followed by estradiol in group VI. Serum creatinine, blood urea nitrogen, and endocrine functions of kidney were measured. Tissue samples were examined both microscopically for beta estrogen receptors and ultrastructurally for cell changes. Groups II, IV & VI showed a significant increase in creatinine, blood urea nitrogen, renal malondialdehyde, renal erythropoietin, plasma renin and plasma prostaglandin E2 and a significant decrease in renal antioxidants and serum vitamin D3. Groups III &V had a significant decrease in creatinine, blood urea nitrogen, renal malondialdehyde and renal erythropoietin with an increase in renal antioxidants, plasma prostaglandin E2 and serum vitamin D3. Histopathological and ultrastructural examinations revealed atrophic tubular changes in group II. The changes were less marked in groups III &V and more extensive in groups IV & VI. Estrogen receptor beta staining showed progressively increased expression in the absence of estrogen. Structural and most endocrine functions of the kidney were significantly affected by estradiol deficiency. Estradiol replacement exhibited a protective effect on renal tissue and endocrine functions.


Assuntos
Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios/métodos , Rim/metabolismo , Menopausa/efeitos dos fármacos , Animais , Antagonistas de Estrogênios/administração & dosagem , Feminino , Rim/efeitos dos fármacos , Rim/patologia , Menopausa/metabolismo , Modelos Animais , Ovariectomia/efeitos adversos , Ratos , Tamoxifeno/administração & dosagem
13.
Theriogenology ; 136: 43-46, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31242457

RESUMO

The effect of the continuous presence of sexually active Rasa Aragonesa rams on the plasma luteinizing-hormone (LH) concentrations of ewes was studied from November to May. Light-treated rams were rendered sexually active (SA rams) by exposure to 2 months of artificially long days (16 h light/8 h dark) in one of two groups from either 1 November (SAR1, n = 3) or 1 December (SAR2, n = 3). Rams (n = 6) in a Control group were kept under the natural photoperiod. Thirty ewes were ovariectomized in September and implanted with a subcutaneous implant (l = 15 mm) that contained estradiol-17ß. One group of ewes (SAR; n = 10) was housed with control rams from 1 October to 15 February before being housed with SAR1 rams from 16 February to 31 March, and with SAR2 rams from 1 April to 31 May. A second group of ewes (C; n = 10) remained with control rams throughout the experiment, and a third group was kept isolated from rams throughout the experiment (ISO; n = 10). Blood samples were collected weekly from November to May, and plasma LH concentrations were measured. In the breeding season (November-February), plasma LH concentrations of ewes did not differ significantly between groups (SAR: 2.00 ±â€¯0.34; C: 1.88 ±â€¯0.16; ISO: 1.67 ±â€¯0.51 ng/ml). From March to May (seasonal anestrus), however, LH plasma concentrations decreased in the C and ISO groups (1.30 ±â€¯0.20 and 0.48 ±â€¯0.04 ng/ml, respectively), but remained at the same level as in the breeding season in the SAR group (2.30 ±â€¯0.17 ng/ml; P < 0.001). Significant differences (P < 0.01) between groups were observed from March onwards: LH concentrations were highest in SAR ewes (P < 0.001) and lowest in the ISO ewes. In conclusion, the continuous presence of sexually active rams prevented the seasonal decrease in plasma LH concentrations, probably by preventing the seasonal negative feedback of estradiol on LH secretion.


Assuntos
Estradiol/farmacologia , Hormônio Luteinizante/metabolismo , Fotoperíodo , Estações do Ano , Comportamento Sexual Animal , Ovinos , Animais , Implantes de Medicamento , Estradiol/administração & dosagem , Feminino , Masculino , Ovariectomia
14.
J Assist Reprod Genet ; 36(8): 1639-1648, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31250175

RESUMO

PURPOSE: This study was undertaken to compare semen quality, hormonal status, and social factors in transgender women seeking fertility preservation with those of fertile cisgender men. Long-range goals are to establish standard practice measures ensuring optimum semen quality for cryopreservation and fertility preservation in transgender women. METHODS: This is a case-control study carried out at an academic medical center. Cases are transgender women seeking fertility preservation prior to initiation of hormone therapy. Controls are cisgender men recently fathering a child. All participants completed the Depression Anxiety Stress Scales 21 survey and additional survey questions related to personal behaviors. Complete semen analysis was carried out in a clinical andrology laboratory according to WHO guidelines, 5th edition. Serum follicle stimulating hormone, estradiol, and testosterone were measured at the time of semen analysis. RESULTS: Sperm concentration, total sperm per ejaculate, total motile sperm, volume, and normal sperm morphology were significantly lower in transgender females compared with fertile cisgender men. Other measures of semen parameters and hormone concentrations were not different between groups. Survey results indicated transgender women were more likely to have symptoms of depression, anxiety, and stress and utilize tucking and tight undergarments, compared with controls; however, both groups reported similar numbers of ejaculations per week. CONCLUSIONS: Although semen parameters were low, cryopreservation of sperm prior to hormone therapy is a viable fertility preservation option for most transgender women. The etiology of the differences in semen parameters is not known. Enhanced education related to personal behaviors or treatment to reduce effects of stressors prior to cryopreservation may improve future fertility potential.


Assuntos
Criopreservação , Estradiol/sangue , Preservação da Fertilidade , Motilidade Espermática/fisiologia , Testosterona/sangue , Pessoas Transgênero/estatística & dados numéricos , Adulto , Estudos de Casos e Controles , Ejaculação , Estradiol/administração & dosagem , Feminino , Humanos , Masculino , Projetos Piloto , Análise do Sêmen , Testosterona/administração & dosagem
15.
Methods Mol Biol ; 1997: 413-429, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31119637

RESUMO

Mouse models of infection are important tools in the study of infectious disease or host the development of products to prevent or treat infections. The estradiol-treated mouse model of Neisseria gonorrhoeae genital tract infection has proved to be a valuable system for determining the importance of gonococcal factors that mediate evasion of host innate effectors in vivo or host gonococcal adaptation to hormonally driven host factors in females. Examination of mechanisms that Neisseria gonorrhoeae uses to subvert the host immune response also has been greatly aided by this whole model system, as have studies on the consequence of antibiotic resistance mutations on gonococcal fitness in vivo and the search for new antibiotics to treat antibiotic-resistant infections. The strict human specificity of N. gonorrhoeae limits the ability of experimental murine infection to mimic human infection. However, in recent years, the development of transgenic mice and protocols for supplementing mice with human factors has improved animal modeling of gonorrhea. To date, however, because the mouse estrous cycle is much shorter than the human reproductive cycle, all reported gonorrhea mouse models require treatment with estradiol and antibiotics to maintain an estrus-like state and suppress the overgrowth of inhibitory commensal flora that occurs under the influence of estrogen to allow sustained N. gonorrhoeae infection. In this chapter, we detail the methods used to (1) prepare the mice for experimental infection with N. gonorrhoeae, (2) inoculate mice and quantitatively culture vaginal swabs for noncompetitive and competitive infection experiments, and (3) monitor the host innate immune response to infection.


Assuntos
Modelos Animais de Doenças , Gonorreia/imunologia , Neisseria gonorrhoeae/imunologia , Animais , Antibacterianos/administração & dosagem , Estradiol/administração & dosagem , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/imunologia , Feminino , Gonorreia/microbiologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/patogenicidade , Vagina/imunologia , Vagina/microbiologia
16.
Reprod Domest Anim ; 54(8): 1149-1154, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31134689

RESUMO

We aimed to evaluate the reproductive performance of Nelore lactating cows submitted to a resynchronization 12 days after timed artificial insemination (TAI) with or without a long-acting progesterone (P4-LA) treatment. Nelore cows were submitted to a P4/oestradiol-based TAI protocol (D0 = insemination). On D12, cows in the control group (n = 184) received a new P4 intravaginal device (0.96 g), whereas cows in the P4-LA group (n = 192) received the P4 device and 75 mg P4-LA. Cows identified as non-pregnant (n = 120) by regression of corpus luteum using colour Doppler ultrasonography on D20 had the P4 device removed and received 500ug of sodium cloprostenol, 1 mg of oestradiol cypionate and 300 IU of eCG and were re-inseminated on D22. There was no difference (p > 0.10) in the pregnancy rate at D20, D30 and D60 after first TAI between the control (69%, 59.7% and 57%, respectively) and P4-LA (67%, 55.7%, and 55.2%, respectively) groups. Pregnancy losses were similar between both groups (p > 0.1). For cows submitted to the second TAI, the pre-ovulatory follicle size did not differ (p > 0.1), but the oestrous detection and pregnancy rates were greater (p < 0.05) in the P4-LA group (92.2% [59/64] and 60.9% [39/64], respectively) than in controls (75% [42/56] and 44.6% [25/56]). The cumulative pregnancy rate after two TAIs did not differ (p > 0.1) between control (73.3% [135/184]) and P4-LA (76% [146/192]) groups. The use of P4-LA at 12 days after TAI potentially increases the pregnancy rates for a new early resynchronization strategy associated with the Doppler imaging for pregnancy diagnosis and results in an alternative to perform two TAIs in 22 days in beef cows.


Assuntos
Bovinos , Sincronização do Estro/métodos , Inseminação Artificial/veterinária , Ovulação/fisiologia , Progesterona/farmacologia , Administração Intravaginal , Animais , Cloprostenol/administração & dosagem , Cloprostenol/farmacologia , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Femininos/farmacologia , Preparações de Ação Retardada , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Estradiol/farmacologia , Feminino , Luteolíticos/administração & dosagem , Luteolíticos/farmacologia , Gravidez , Progesterona/administração & dosagem , Progestinas/administração & dosagem , Progestinas/farmacologia
17.
Reprod Domest Anim ; 54(7): 1050-1053, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31095778

RESUMO

The aim of this study was to develop a resynchronization strategy before the return of oestrus in cows diagnosed as not pregnant after fixed-time artificial insemination (TAI). A total of 839 cows, approximately 45 days post-partum, were synchronized using TAI. On day 0, intravaginal progesterone-releasing devices were inserted and 2 mg of oestradiol benzoate was administered. Eight days later (D8), the progesterone-releasing devices were removed and oestradiol cypionate (0.5 mg, eCG [300 IU]) and prostaglandin (7.5 mg) were administered. All cows were inseminated between 48 and 56 hr after device removal (D10). Thirty days after TAI, cows that were not diagnosed as pregnant by ultrasound were immediately resynchronized and again inseminated at a fixed time. The hormonal protocol used in the first and second rounds of TAI was the same. The pregnancy rate after the first TAI was 52%, and after the second TAI, it was 49%. The increase in the total pregnancy rate (synchronization + second oestrous synchronization) compared to a single synchronization was 23.5%. In conclusion, resynchronization of oestrus and ovulation in zebu cows that had previously undergone TAI protocols is effective in increasing the reproductive efficiency.


Assuntos
Sincronização do Estro/métodos , Inseminação Artificial/veterinária , Animais , Bovinos , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Feminino , Inseminação Artificial/métodos , Ovulação/efeitos dos fármacos , Gravidez , Taxa de Gravidez , Progesterona/administração & dosagem
18.
Eur J Contracept Reprod Health Care ; 24(3): 209-215, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31066303

RESUMO

Purpose: Prior studies evaluating the effect of administered progestogens on peak cervical mucus have not controlled for the influence of endogenous hormones. To address this, we treated women with a gonadotropin-releasing hormone (GnRH) agonist to suppress the hypothalamus-pituitary-ovarian (HPO) axis and used transdermal oestradiol replacement to stimulate peak cervical mucus and then evaluated the effects of an oral progestin or oestradiol withdrawal. Materials and methods: We used a crossover design to examine cervical mucus changes in women receiving transdermal oestradiol replacement following intramuscular administration of leuprolide acetate. After increasing oestradiol patches to mid-cycle levels, subjects were assigned to either 0.35 mg oral norethindrone with continuation of the patches (NET) or oestradiol withdrawal by patch removal (E2WD). We collected serum and cervical mucus samples at 0, 2, 4, 6, 22 and 24 h following the intervention. Results: We analysed 12 cycles (6 NET, 6 E2WD) from three subjects. Baseline cervical mucus scores were favourable to sperm penetration [NET median 11, interquartile range (9-12), E2WD 13 (12-13)]. Two hours after removal of oestradiol patch or administration of norethindrone, cervical mucus scores declined [NET 8.5 (4-9), E2WD 10.5 (10-12)]. Low cervical mucus scores persisted at 24 h with NET [8.0 (7-8)] but not E2WD [10.5 (8-11)]. Conclusions: We observed a rapid decline in cervical mucus Insler scores following administration of a single dose of oral norethindrone, and scores remained lower and unfavourable through 24 h. Oestradiol withdrawal did not result in similar unfavourable changes.


Assuntos
Muco do Colo Uterino/efeitos dos fármacos , Colo do Útero , Anticoncepcionais Orais Hormonais/farmacologia , Estradiol/farmacologia , Leuprolida/farmacologia , Progestinas/farmacologia , Adulto , Estudos Cross-Over , Estradiol/administração & dosagem , Estradiol/sangue , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Humanos , Muco , Noretindrona/sangue , Noretindrona/farmacologia , Projetos Piloto , Progesterona/sangue , Adesivo Transdérmico , Adulto Jovem
19.
Animal ; 13(10): 2305-2312, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30982488

RESUMO

Expression of estrus near timed artificial insemination (TAI) is associated with greater fertility, and estrus detection could improve TAI fertility or direct TAI management, although accurate estrus detection can be difficult and time-consuming using traditional methods. The aim of this study is to evaluate influence of estrus on pregnancy (artificial insemination pregnancy rates (P/AI)) and to validate an alternative method to classify estrus/heat expression using tail chalking (HEATSC) in postpartum Bos indicus cows subjected to TAI in progesterone-estrogen-based protocols. In experiment 1 (Exp. 1), cows (5491) were subjected to visual observation of estrus after progesterone device removal, before TAI, and P/AI was evaluated according to estrus and body condition score (BCS). Cows received a progesterone device and 2 mg estradiol benzoate (EB). After 8 days, the device was removed and 150 µg of d-cloprostenol and 300 IU equine chorionic gonadotrophin was given. Later, animals in Exp. 1 received 1 mg EB and TAI 44 to 48 h. In the Exp. 2 - 3830 cows using similar protocol, received different ovulation inducers: 1 mg EB (n=1624) or 1 mg estradiol cypionate (EC; n=2206) on day 8 (D8). Cows were then marked with chalk, and HEATSC evaluated at TAI on D10 (HEATSC1 - no chalk removal=no estrus expression; HEATSC2 - partial chalk removal=low estrus expression; HEATSC3 - near complete/complete chalk removal=high estrus expression). In Exp. 1, cows showing estrus presented greater P/AI (48.4% v. 40.2%, P<0.05). In Exp. 2, P/AI (HEATSC1 - 40.0%; HEATSC2 - 49.7%; HEATSC3 - 60.9%; P<0.001), and larger follicle timed artificial insemination (LFTAI) (<0.001) varied according to HEATSC. There was no difference in P/AI (P=0.41) or LFTAI (P=0.33) according to ovulation inducer. Cows with greater BCS showed greater P/AI in both experiments (P<0.05). Estrus presence and greater HEATSC improved P/AI, and EC v. EB used promoted differential estrus manifestation (cows showing HEATSC2 and HEATSC3: 79.5% with EB v. 69.98% with EC use, P<0.001), however, with similar P/AI. The use of HEATSC in B. indicus cows subjected to TAI is useful to identify cows with greater estrus expression and consequently improved pregnancy rates in TAI, allowing the cows with low HEATSC to be targeted for additional treatments aimed at improving P/AI.


Assuntos
Bovinos/fisiologia , Estradiol/administração & dosagem , Estrogênios/administração & dosagem , Progesterona/administração & dosagem , Reprodução/efeitos dos fármacos , Animais , Estro/efeitos dos fármacos , Detecção do Estro , Feminino , Fertilidade/efeitos dos fármacos , Temperatura Alta , Inseminação Artificial/veterinária , Folículo Ovariano/efeitos dos fármacos , Indução da Ovulação , Gravidez , Taxa de Gravidez
20.
Fertil Steril ; 111(6): 1177-1185.e3, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31029432

RESUMO

OBJECTIVE: To investigate whether the duration of estrogen administration before euploid embryo transfer affects clinical outcome. DESIGN: Retrospective cohort study. SETTING: Private, academic fertility center. PATIENT(S): Patients (n = 1,439) undergoing autologous freeze-only in vitro fertilization with preimplantation genetic testing (PGT) followed by endometrial preparation with estrogen and progesterone in a frozen, euploid blastocyst transfer cycle. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcome was live birth, and secondary outcomes included implantation, clinical pregnancy, early pregnancy loss, live birth, infant birthweight, low birth weight, infant gestational age at delivery, and preterm birth. RESULT(S): The duration of estrogen administration (mean: 17.5 ± 2.9 days; range: 10-36 days) before frozen embryo transfer did not impact implantation (odds ratio [OR] 0.99; 95% confidence interval [CI], 0.95-1.03), clinical pregnancy (OR 0.98; 95% CI, 0.94-1.01), early pregnancy loss (OR 1.03; 95% CI, 0.95-1.12), or live birth (OR 0.99; 95% CI, 0.95-1.03). The duration of estrogen exposure did not affect infant birthweight (in grams) (ß= -10.65 ± 8.91) or the odds of low birth weight (OR 0.87; 95% CI, 0.68-1.13). For every additional day of estrogen administration, we observed a reduction in gestational age at delivery (in weeks) (ß= -0.07 ± 0.03), but the odds of preterm delivery were not affected (OR 1.05; 95% CI, 0.95-1.17). CONCLUSION(S): Variation in the duration of estradiol supplementation before progesterone initiation does not impact frozen, euploid blastocyst transfer outcome. The duration of estrogen administration was inversely correlated with gestational age at delivery, but this did not translate into an increase in preterm delivery. Further studies are required on the downstream effects of endometrial preparation on the placental-endometrium interface.


Assuntos
Blastocisto , Criopreservação , Implantação do Embrião/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Estradiol/administração & dosagem , Fármacos para a Fertilidade Feminina/administração & dosagem , Fertilização In Vitro , Infertilidade/terapia , Transferência de Embrião Único , Adulto , Esquema de Medicação , Endométrio/fisiopatologia , Estradiol/efeitos adversos , Feminino , Fármacos para a Fertilidade Feminina/efeitos adversos , Humanos , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Nascimento Vivo , Gravidez , Complicações na Gravidez/etiologia , Taxa de Gravidez , Estudos Retrospectivos , Fatores de Risco , Transferência de Embrião Único/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Vitrificação
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