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OBJECTIVE: To investigate the complete metabolic and phenotypic profiles of a large cohort of untreated, consecutively recruited Korean women with polycystic ovary syndrome (PCOS), for whom a registry for Korean women with PCOS was constructed. DESIGN: Observational study. SETTING: Three infertility clinics and 10 university hospitals. PATIENT(S): Eight hundred sixty-five women with PCOS were recruited using the Rotterdam criteria. INTERVENTION(S): Standardized evaluation protocol and web-based case report form. MAIN OUTCOME MEASURE(S): Metabolic and phenotypic profiles. RESULT(S): The subjects with PCOS mainly consisted of young and nonobese women. The most problematic subjective symptom was menstrual disturbance or infertility, and, on average, the patients seemed to menstruate every 2 months. PCO morphology was observed in 96.5% of the patients. Although few women visited hospitals owing to HA symptoms alone, hirsutism was observed in one-third of the patients (33.9%) and half (47.4%) of the patients had biochemical HA. About one-fifth (20.1%) of the patients had generalized obesity, and one-third (33.2%) had central obesity. Prevalence of dyslipidemia, diabetes, hypertension, and metabolic syndrome were 35.7%, 3.5%, 4.0%, and 13.7%, respectively. Prevalence of prediabetes was 20.8%, and a substantial proportion of additional subjects with normal fasting plasma glucose or oral glucose tolerance tests were identified as having prediabetes by hemoglobin A1C testing. CONCLUSION(S): Our well-defined cohort provided comprehensive estimates of the features of metabolic and phenotypic profiles related to PCOS in Korean women. Further longitudinal follow-up studies are needed to investigate the changes in phenotypic and metabolic markers in this PCOS cohort.
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Povo Asiático/genética , Metaboloma/genética , Fenótipo , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Adolescente , Adulto , Povo Asiático/etnologia , Estudos de Coortes , Feminino , Teste de Tolerância a Glucose/tendências , Humanos , Resistência à Insulina/fisiologia , Síndrome Metabólica/etnologia , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Metaboloma/fisiologia , Síndrome do Ovário Policístico/etnologia , República da Coreia/etnologia , Adulto JovemRESUMO
The study aimed to investigate the effect of imatinib coadministration on in vitro oocyte acquisition and subsequent embryo development in cyclophosphamide (Cp)-treated mice. Female BDF1 mice were injected with 5 IU equine chorionic gonadotropin (eCG) followed by 5 IU human chorionic gonadotropin 48 hours later and then oocytes were retrieved 14 hours later. Twenty-four hours prior to eCG administration, 25, 50, or 75 mg/kg Cp with or without 7.5 mg/kg imatinib was injected. In the 25 and 50 mg/kg Cp groups, imatinib coadministration significantly enhanced the percentage of mature oocytes (+16.4% and +10.4%) and significantly decreased the percentage of dead oocytes (-25.9% and -15.3%). Imatinib coadministration significantly enhanced the fertilization rate (FR) in the 50 mg/kg Cp group (+12.2%). Intraoocyte spindle integrity was significantly affected by Cp and was rescued by imatinib coadministration. Coadministration of imatinib prior to ovarian stimulation has the benefit of enhancing oocyte maturity and the in vitro FR in Cp-treated mice .
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OBJECTIVE: To assess the efficacies of once-weekly bisphosphonates on bone mineral density (BMD) gains in Korean women aged 50 years or more. METHODS: We selected 166 patients who received: alendronate 70 mg (n=48), alendronate 70 mg + cholecalciferol 2,800 IU (n=31) or risedronate 35 mg (n=87) for one year. The baseline BMD and the % changes of BMD at one-year were compared among the three medication groups. RESULTS: The menopausal status and number of women with osteoporosis was not different among the three groups, but mean age of women was significantly lower in alendronate group. Baseline BMD at L1-4 and femur neck (FN) was similar, but baseline BMD at femur total (FT) was significantly lower in alendronate group. After one-year use, the median % changes of BMD at three sites were similar among the three groups; however, the median values were highest in alendronate + cholecalciferol group (L1-4: 4.48%, 6.74%, and 4.50%; FT: 2.09%, 3.70%, and 2.31%; FN: 3.05%, 3.79%, and 2.03%). CONCLUSION: Among three once-weekly bisphosphonates, BMD gains were highest after one-year use of alendronate+cholecalciferol, although statistically not significant.
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OBJECTIVE: Metabolic disturbances are well-recognized clinical features of polycystic ovary syndrome (PCOS). Carotid intima-media thickness (CIMT) has been widely used as a surrogate marker of atherosclerosis and cardiovascular disease (CVD). CIMT in women with PCOS has been investigated in many studies, but there has been only one report in the Korean population. The aim of the present study was to compare the presence of subclinical atherosclerosis in young untreated Korean women with PCOS and age-matched controls, specifically by measuring their CIMT. METHODS: CIMT was measured by one radiologist in 56 PCOS patients and 56 controls. To compare the CIMT according to PCOS phenotypes, women with PCOS were divided into two subgroups according to the presence of hyperandrogenism. RESULTS: Although PCOS patients were more obese and had higher blood pressure and insulin resistance index than the age-matched controls, the CIMT was not different between the two groups (0.49 ± 0.09 mm in PCOS patients vs. 0.50 ± 0.11 mm in controls, respectively, p = 0.562). When the CIMT in the control group was compared with hyperandrogenic and non-hyperandrogenic PCOS groups, also no significant differences were found. CONCLUSION: Despite the significant differences in some vascular risk factors between women with PCOS and controls, PCOS patients did not have a significantly higher CIMT (even in the hyperandrogenic subgroups). Although our study did not show the increased risk of subclinical atherosclerosis in PCOS patients, the role of CIMT continues to be investigated considering the importance of screening and monitoring CVD risk factors in women with PCOS.
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STUDY QUESTION: Do microRNAs (miRNAs) in granulosa cells (GCs) affect oocyte maturation during ovarian follicle development? SUMMARY ANSWER: Sophisticated regulation by miRNAs in ovarian GCs may improve oocyte maturation efficiency during ovarian follicle development. WHAT IS KNOWN ALREADY: The meiotic competence of oocytes depends on the follicle's potential to undergo appropriate maturation and is an important factor in infertility therapies such as IVF. The exact function of the GCs during follicular development remains unknown. STUDY DESIGN, SIZE, DURATION: After in vitro maturation (IVM) and ovulation induction of isolated ovarian pre-antral follicles from 12-day-old female C57BL6 mice (n = 40), miRNA expression in the GCs was compared according to the maturity of the oocyte (metaphase I (MI) versus metaphase II (MII)). The miRNAs, which showed notable different expression, were modulated by transfection during IVM of follicles. MATERIALS, SETTING, METHODS: miRNA expression and candidate target gene expression in GCs of isolated murine ovarian pre-antral follicles were evaluated by real-time PCR after IVM. miR mimics and -inhibitors for selected miRNAs were transfected into the in vitro-maturated follicles, and ovulation, oocyte maturation and fertilization rates were compared. Candidate target gene expressions in GC were evaluated by quantitative PCR and immunohistochemistry using confocal microscopy. MAIN RESULTS AND THE ROLE OF CHANCE: The relative expression of mmu-let-7b (0.78 ± 0.10, P = 0.016), mmu-let-7c (0.78 ± 0.12, P = 0.029), mmu-miR-27a (0.57 ± 0.18, P = 0.016) and mmu-miR-322 (0.59 ± 0.14, P = 0.008) was significantly lower in the GCs of follicles containing MII oocytes compared with those of MI oocytes. Transfection with a mmu-miR-27a-mimic sequence decreased the oocyte maturation rate compared with that for the control (9.4 versus 18.9%, P = 0.042), and transfection with mmu-let-7c-, mmu-miR-27a- and mmu-miR-322-inhibitor sequences increased the oocyte maturation rate by 1.5- to 2.0-folds compared with that for the control (40.6, 31.6, and 30.5%versus 18.9%, P < 0.001, P = 0.013, P = 0.021, respectively). The expression of IGFBP-2 was higher in GCs of MII than in the GCs of MI, and higher in miR-inhibitor transfection groups than in miR-mimic transfection groups and controls. LIMITATIONS, REASONS FOR CAUTION: An in vitro model was used in lieu of an in vivo model because of the ease of performing miRNA transfection in cell culture. However, studies have shown similarities and differences in in vivo versus in vitro cultured follicles. The findings of the present study need to be confirmed using in vivo maturation models and extended to evaluate developmental competence. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that sophisticated miRNA regulation in GCs may improve oocyte maturation efficiency during ovarian follicle development. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A111539). None of the authors has any conflicts of interest to declare.
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Técnicas de Maturação in Vitro de Oócitos , Meiose/genética , MicroRNAs/fisiologia , Folículo Ovariano/crescimento & desenvolvimento , Animais , Gonadotropina Coriônica/farmacologia , Feminino , Fertilização in vitro , Células da Granulosa/metabolismo , Células da Granulosa/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , TransfecçãoRESUMO
OBJECTIVE: The aim of this study was to investigate the effect of insulin sensitizing agents on hormonal and metabolic parameters as well as menstrual patterns in women with polycystic ovary syndrome (PCOS). METHODS: One hundred and twenty-three patients with PCOS were included. Metformin was administered to patients at 1,500 mg or 1,700 mg daily for 3 months. If the patients had no improvement of the menstrual cycle or metformin-related adverse effects developed, the patients changed medication to a daily dose of either 15 mg pioglitazone or up to 45 mg. Then resumption of a regular menstrual cycle or recovery of ovulation was evaluated. Hormonal and metabolic profiles were compared between the response and non-response group to insulin sensitizing agents. RESULTS: One hundred and five patients with PCOS were treated with metformin for 3 months. Forty-eight patients (45.7%) showed improvement of menstrual cycle regularity after 3 months of metformin use, whereas 57 patients (54.3%) had no change. The mean free testosterone measured after 3 months of treatment was significantly lower in metformin responders than in non-responders. The other parameters did not differ between the groups. Of the 23 patients who used pioglitazone for 3 to 6 months, 19 patients (82.6%) showed improvement in their menstrual cycles. CONCLUSION: Metformin treatment seems to be effective for the improvement of menstrual cyclicity irrespective of insulin resistance in women with PCOS. When metformin related adverse effect occurred, pioglitazone would be effective for aiding the resumption of the menstrual cycle.
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OBJECTIVE: The aim of the present study was to examine the relationship among male age, strict morphology, and sperm chromatin structure and condensation. METHODS: Sperm samples from a total of 100 men underwent semen analysis, and sperm chromatin structure and condensation were assessed with toluidine blue (TB) and aniline blue (AB) tests. RESULTS: Prevalence of strict morphology of less than 4%, and abnormal sperm chromatin structure and condensation did not show any statistically significant differences according to male age (p=0.605, p=0.235, and p=0.080). No significant correlation was demonstrated among age of male partners, strict morphology, and abnormal sperm chromatin structure using TB and AB tests. However, abnormal sperm chromatin condensation was positively associated with sperm chromatin structure (r=0.594, p=0.000) and showed negative correlation with strict morphology (r=-0.219, p=0.029). CONCLUSION: The tests for sperm chromatin condensation showed a significant association with strict morphology. Further study is needed to elucidate the relationship between clinical outcome and sperm chromatin tests.
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OBJECTIVE: To investigate the influence of laparoscopic surgery on the natural conception rate in infertile women with endometriosis during the first year after the operation. METHODS: We retrospectively studied 43 infertile women with surgically proven endometriosis. The natural conception rate was investigated for the 12 months after the laparoscopy. RESULTS: The overall pregnancy rate was 41.9% (18/43). 66.7% (12/18) and 94.4% (17/18) of the patients conceived within postoperative 3 months and 6 months, respectively. The spontaneous pregnancy rate was not associated with the severity of endometriosis or laparoscopic findings or the type of surgery. The pregnancy rate for stage IV was relatively low (20.0%) compared to stage I, II, and III (35.7%, 44.4%, and 53.3%, respectively), although it did not reach statistical significance. CONCLUSION: Conservative surgical treatment with laparoscopy and a prompt attempt at natural conception may be effective for infertile patients with endometriosis.
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Hypochondroplasia (HCH) is an autosomal dominant inherited skeletal dysplasia, usually caused by a heterozygous mutation in the fibroblast growth factor receptor 3 gene (FGFR3). A 27-year-old HCH woman with a history of two consecutive abortions of HCH-affected fetuses visited our clinic for preimplantation genetic diagnosis (PGD). We confirmed the mutation in the proband (FGFR3:c.1620C>A, p.N540K), and established a nested allele-specific PCR and sequence analysis for PGD using single lymphocyte cells. We performed this molecular genetic analysis to detect the presence of mutation among 20 blastomeres from 18 different embryos, and selected 9 embryos with the wild-type sequence (FGFR3:c.1620C). A successful pregnancy was achieved through a frozen-thawed cycle and resulted in the full-term birth of a normal neonate. To the best of our knowledge, this is the first report of a successful pregnancy and birth using single-cell allele-specific PCR and sequencing for PGD in an HCH patient.
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Great advances have been made in the field of assisted reproductive technology (ART) since the first in vitro fertilization (IVF) baby was born in Korea in the year of 1985. However, it deserve to say that the invaluable data from fertility centers may serve as a useful source to find out which factors affect successful IVF outcome and to offer applicable information to infertile patients and fertility clinics. This article intended to report the status of ART in 2009 Korean Society of Obstetrics and Gynecology surveyed. The current survey was performed to assess the status and success rate of ART performed in Korea, between January 1 and December 31, 2009. Reporting forms had been sent out to IVF centers via e-mail, and collected by e-mail as well in 2012. With International Committee Monitoring Assisted Reproductive Technologies recommendation, intracytoplasmic sperm injection (ICSI) and non-ICSI cases have been categorized and also IVF-ET cases involving frozen embryo replacement have been surveyed separately. Seventy-four centers have reported the treatment cycles initiated in the year of 2009, and had performed a total of 27,947 cycles of ART treatments. Among a total of 27,947 treatment cycles, IVF and ICSI cases added up to 22,049 (78.9%), with 45.3% IVF without ICSI and 54.7% IVF with ICSI, respectively. Among the IVF and ICSI patients, patients confirmed to have achieved clinical pregnancy was 28.8% per cycle with oocyte retrieval, and 30.9% per cycle with embryo transfer. The most common number of embryos transferred in 2009 is three embryos (40.4%), followed by 2 embryos (28.4%) and a single embryo transferred (13.6%). Among IVF and ICSI cycles that resulted in multiple live births, twin pregnancy rate was 45.3% and triple pregnancy rate was 1.1%. A total of 191 cases of oocyte donation had been performed to result in 25.0% of live birth rate. Meanwhile, a total of 5,619 cases of frozen embryo replacement had been performed with 33.7% of clinical pregnancy rate per cycle with embryo transfer. When comparing with international registry data, clinical pregnancy rate per transfer from fresh IVF cycles including ICSI (34.1%,) was comparable to clinical pregnancy rate per transfer in European Society for Human Reproduction and Embryology report was 32.5% though lower than 45.0% for USA data. There was no remarkable difference in status of assisted reproductive technology in Korea between the current report and the data reported in 2008. The age of women trying to get pregnant was reconfirmed to be the most important factor that may have impact on success of ART treatment.
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In this study, we examined the in vivo osteogenic differentiation of human embryoid bodies (hEBs) by using an injectable in situ-forming hydrogel. A solution containing MPEG-b-(polycaprolactone-ran-polylactide) (MCL) and hEBs was easily prepared at room temperature. The MCL solution with hEBs and osteogenic factors was injected into nude mice and developed into in situ-forming hydrogels at the injection sites; these hydrogels maintained their shape even after 12 weeks in vivo, thereby indicating that the in situ-forming MCL hydrogel was a suitable scaffold for hEBs. The in vivo osteogenic differentiation was observed only in the in situ gel-forming MCL hydrogel in the presence of hEBs and osteogenic factors. In conclusion, this preliminary study suggests that hEBs and osteogenic factors embedded in an in situ-forming MCL hydrogel may provide numerous benefits as a noninvasive alternative for allogeneic tissue engineering applications.
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OBJECTIVES: Only a few studies have suggested the association between ovarian cysts and serum estrogen levels during tamoxifen use. However, increased estrogen levels with ovarian cysts would affect the prognosis of breast cancer; this association has not yet been studied. We aimed to investigate the association between ovarian cysts and prognostic markers in premenopausal breast cancer patients undergoing tamoxifen treatment. METHODS: A retrospective review of 65 premenopausal breast cancer patients who underwent tamoxifen treatment was performed. Serum hormone levels were measured either specifically between cycle days 2 and 5 in menstruating patients or at any time in amenorrheic participants. RESULTS: The study population consisted of premenopausal patients with (n = 23) and without ovarian cysts (n = 42). Serum estradiol (E(2)) levels and tumor markers were not statistically different based on ovarian cyst status. In the subgroup analysis, serum E(2) levels were significantly higher in menstruating women with ovarian cysts, and E(2) levels were positively correlated with serum cancer antigen 15-3 and insulin-like growth factor-1 in these women. CONCLUSIONS: Ovarian cysts during tamoxifen use may affect the markers associated with the clinical course of premenopausal breast cancer.
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Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Cistos Ovarianos/sangue , Cistos Ovarianos/induzido quimicamente , Pré-Menopausa/sangue , Tamoxifeno/efeitos adversos , Adulto , Amenorreia/sangue , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Biomarcadores Tumorais/sangue , Estradiol/sangue , Feminino , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Menstruação/sangue , Pessoa de Meia-Idade , Mucina-1/sangue , Prognóstico , Estudos Retrospectivos , Tamoxifeno/administração & dosagemRESUMO
Human embryonic stem cells are derived from the inner cell mass of preimplantation embryo at the blastocyst stage and their differentiation occurs through an intermediate step involving the formation of embryoid bodies (EBs), which are aggregates of embryonic stem cells. The EBs seem to be a powerful tool for investigating the development of embryos, as they can mimic the initial stages of embryonic development. In this study, we aimed to investigate the effect of estrogen compounds on the proliferation and differentiation of short-term and long-term cultured EBs in vitro. For this study, 10-day-old (short-term cultured) and 30-day-old (long-term cultured) EBs were subjected to estradiol (E2), estriol (E3), selective estrogen receptor modulator (raloxifene [RLX]), bisphenol A, and 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole for 7 days. To confirm the effects of estrogen treatment, ICI-182780 was added to the respective EBs for additional 7 days following estrogen treatment. Quantitative reverse transcription-polymerase chain reaction was performed to analyze the relative expression of differentiation marker genes representing the 3 germ layers. The expression of 7 marker genes, which included α-fetoprotein, hepatocyte nuclear factor (HNF)-3ß, HNF-4α (endoderm), brachyury, cardiac actin ([cACT]; mesoderm), nestin (ectoderm), and Oct-4 (undifferentiated), was measured. Significantly, lower expression of HNF-4α in both short-term and long-term cultured EBs was observed after treatment of estrogen compounds compared to control. The expression of HNF-3ß in short-term cultured EBs has been positively affected by E2, E3, and RLX. Regarding cACT, higher expression was observed after treatment of E2 (10(-7) mol/L) and E3 (10(-9) mol/L) in short-term cultured EBs, but opposite effects were demonstrated in long-term cultured EBs. The lower expressions of HNF-4α by E2 and RLX were negated by ICI-182780 treatment, although these findings were not statistically significant in E3-treated group. These findings suggest that estrogen compounds have effects on endodermal and mesodermal differentiation of human EBs.
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Corpos Embrioides/efeitos dos fármacos , Estrogênios/farmacologia , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Corpos Embrioides/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Marcadores Genéticos , Humanos , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de TempoRESUMO
Gonadotropins including follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play a crucial role in human-assisted reproduction techniques. Despite wide use of recombinant gonadotropins in clinical practice, the efficacy of urinary gonadotropins and the dosage of LH component have not yet been elucidated. This study was designed to investigate the difference of follicle culture outcomes according to various compositions of gonadotropins during in vitro culture of mouse preantral follicles. Ovaries were obtained from the 14-day-old C57BL/6 mice, and preantral follicles were isolated and cultured in culture media supplemented with human menopausal gonadotropin (hMG) 200 mIU/mL (group 1), recombinant FSH and LH (rFSH + rLH) 200 mIU/mL each (group 2), rFSH 200 mIU/mL + rLH 100 mIU/mL (group 3), or rFSH 200 mIU/mL + rLH 20 mIU/mL (group 4). Follicle survival rate was significantly lower in group 4. Antral follicles in lower doses of LH (groups 3, 4) showed a statistically significant larger diameter and tended to have a higher antral formation rate. However, follicles in group 1 tended to have a higher oocyte maturation rate. Estradiol concentration from conditioned media from 2:1 FSH/LH (group 3) was significantly higher than those from 1:1 FSH/LH (group 2) or 10:1 FSH/LH (group 4). Half dose of rLH to rFSH facilitated upregulation of growth differentiation factor 9 (Gdf9) expression in granulosa cells when compared to 1:1 FSH/LH or 10:1 FSH/LH. Conclusively, recombinant gonadotropins provided a comparable condition to hMG, and half dose of rLH to rFSH seems to be more suitable for follicular development during in vitro culture.
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Hormônio Foliculoestimulante/farmacologia , Técnicas de Maturação in Vitro de Oócitos/métodos , Hormônio Luteinizante/farmacologia , Menotropinas/farmacologia , Folículo Ovariano/efeitos dos fármacos , Animais , Meios de Cultivo Condicionados/metabolismo , Relação Dose-Resposta a Droga , Estradiol/metabolismo , Feminino , Regulação da Expressão Gênica , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Humanos , Menotropinas/urina , Camundongos , Camundongos Endogâmicos C57BL , Folículo Ovariano/metabolismo , Proteínas Recombinantes/farmacologia , Técnicas de Cultura de TecidosRESUMO
Human pluripotent stem cells (hPSCs) have arisen as a source of cells for biomedical research due to their developmental potential. Stem cells possess the promise of providing clinicians with novel treatments for disease as well as allowing researchers to generate human-specific cellular metabolism models. Aging is a natural process of living organisms, yet aging in human heart cells is difficult to study due to the ethical considerations regarding human experimentation as well as a current lack of alternative experimental models. hPSC-derived cardiomyocytes (CMs) bear a resemblance to human cardiac cells and thus hPSC-derived CMs are considered to be a viable alternative model to study human heart cell aging. In this study, we used hPSC-derived CMs as an in vitro aging model. We generated cardiomyocytes from hPSCs and demonstrated the process of aging in both human embryonic stem cell (hESC)- and induced pluripotent stem cell (hiPSC)-derived CMs. Aging in hESC-derived CMs correlated with reduced membrane potential in mitochondria, the accumulation of lipofuscin, a slower beating pattern, and the downregulation of human telomerase RNA (hTR) and cell cycle regulating genes. Interestingly, the expression of hTR in hiPSC-derived CMs was not significantly downregulated, unlike in hESC-derived CMs. In order to delay aging, vitamin C was added to the cultured CMs. When cells were treated with 100 µM of vitamin C for 48 h, anti-aging effects, specifically on the expression of telomere-related genes and their functionality in aging cells, were observed. Taken together, these results suggest that hPSC-derived CMs can be used as a unique human cardiomyocyte aging model in vitro and that vitamin C shows anti-aging effects in this model.
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Envelhecimento/efeitos dos fármacos , Ácido Ascórbico/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Células-Tronco Pluripotentes/efeitos dos fármacos , Envelhecimento/genética , Envelhecimento/metabolismo , Antioxidantes/farmacologia , Diferenciação Celular , Linhagem Celular , Seguimentos , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Microscopia Eletrônica de Transmissão , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/ultraestrutura , Células-Tronco Pluripotentes/metabolismo , Células-Tronco Pluripotentes/ultraestrutura , RNA/genética , Reação em Cadeia da Polimerase em Tempo Real , Proteína 2 de Ligação a Repetições Teloméricas/biossíntese , Proteína 2 de Ligação a Repetições Teloméricas/genéticaRESUMO
OBJECTIVES: To determine if specific single nucleotide polymorphisms (SNPs) in the Epidermal Growth Factor Receptor (EGFR) gene were meaningful markers for the risk of advanced stage endometriosis in a Korean population. STUDY DESIGN: Case-control study in a collective of 299 women with endometriosis and 285 controls. Three polymorphisms (151904 A>T [T628T] on exon 16 [rs 17337023], 162093 G>A [Q787Q] on exon 20 [rs 10251977], and 181946 C>T [D994D] on exon 25 [rs 2293347]) were assessed by a Minor Groove Binder (MGB) primer/probe Taqman assay. In-silico haplotypes were deduced using the Haploview (version 3.32) software package. RESULTS: There were no statistically significant differences in the genotype or haplotype frequencies of the three EGFR polymorphisms between subjects with endometriosis versus the control group. Even when the endometriosis cases were subdivided into stage III and IV based on the ASRM criteria, no statistically significant differences in genotype distribution or haplotype frequencies were observed between the three groups. CONCLUSIONS: Our results suggest that the 151904 A>T, 162093 G>A, and 181946 C>T polymorphisms in the EGFR gene are not associated with advanced stage endometriosis in a Korean population. Our results are in agreement with the results reported by Inagaki et al.
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Endometriose/genética , Receptores ErbB/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Alelos , Estudos de Casos e Controles , Biologia Computacional , Endometriose/sangue , Endometriose/metabolismo , Endometriose/fisiopatologia , Receptores ErbB/metabolismo , Éxons , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Hospitais Universitários , Humanos , República da Coreia , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: It has been suggested that variations in the inhibin α gene (INHA) may affect the ovarian function of women. This study was performed to investigate whether the genetic polymorphisms of the INHA gene are associated with idiopathic premature ovarian failure (POF) in a Korean population. METHODS: The subjects consisted of 159 idiopathic POF patients and 233 post-menopausal controls. Genotyping for the -16C>T polymorphism was performed by an minor groove binder (MGB) primer/probe Taqman assay, and the -124A>G polymorphism was identified using PCR restriction fragment length polymorphism analysis. Haplotypes were deduced by using the Haploview version 4.1. RESULTS: There were no significant differences in the genotype distributions or allele frequencies of the INHA gene -16C>T and -124A>G polymorphisms between the POF and the control group. Haplotype analysis also showed no significant difference between groups. CONCLUSIONS: The distribution of the INHA gene promoter polymorphisms in a Korean POF population was not significantly different from controls, implying that the INHA gene polymorphisms may not be associated with the risk of idiopathic POF.
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Inibinas/genética , Polimorfismo Genético/genética , Insuficiência Ovariana Primária/genética , Regiões Promotoras Genéticas/genética , Adulto , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição/genética , República da CoreiaRESUMO
OBJECTIVE: Insulin resistance is a core feature of polycystic ovary syndrome (PCOS). Recently, genome-wide association studies have reported a number of single-nucleotide polymorphisms (SNPs) with reproducible associations and susceptibilities to type 2 diabetes. We examined the potential association between the diabetogenic genes uncovered in the genome-wide association studies and PCOS in Korean women. DESIGN: Case-control study. PATIENTS: Women with or without PCOS. MEASUREMENTS: DNA samples from 377 patients with PCOS and 386 age-matched controls were genotyped. RESULTS: None of the 12 SNPs in the six genes (KCNJ11, TCF7L2, SLC30A8, HHEX, FTO and CDKAL1) uncovered in the genome-wide association studies were associated with PCOS. For further analysis, the patients with PCOS were divided into two or three subgroups according to genotype, and the associations between the genotypes and insulin resistance or insulin secretory capacity were assessed. No SNPs were significantly associated with HOMA-IR, HOMA (ßcell) (%), or 2-h 75-g oral glucose tolerance test insulin levels in the patients with PCOS; there were no significant associations with other serum hormonal and metabolic markers, such as androgen or glucose levels. CONCLUSIONS: Our results suggest that the six type 2 diabetes-associated genes identified in genome-wide association studies are not associated with PCOS.
Assuntos
Proteínas de Transporte de Cátions/genética , Quinase 5 Dependente de Ciclina/genética , Proteínas de Homeodomínio/genética , Síndrome do Ovário Policístico/genética , Canais de Potássio Corretores do Fluxo de Internalização/genética , Proteínas/genética , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Fatores de Transcrição/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Androgênios/sangue , Povo Asiático/genética , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Resistência à Insulina/genética , Síndrome do Ovário Policístico/metabolismo , Polimorfismo de Nucleotídeo Único , República da Coreia , Fatores de Risco , Transportador 8 de Zinco , tRNA MetiltransferasesRESUMO
BACKGROUND: Recently, the American Diabetes Association (ADA) has included glycated hemoglobin A1(c) (A1C) level as a component of diagnostic criteria of 'diabetes' or 'increased risk for diabetes'. This study was conducted to examine the prevalence of and risk factors for 'elevated A1C' (≥5.7%) in women with polycystic ovary syndrome (PCOS). METHODS: A1C was measured using an immunoturbidimetric assay, and was evaluated in 154 patients with PCOS and 469 age-matched controls (match ratio of 1-3). All subjects were categorized by BMI (non-obese <25 kg/m(2) and obese ≥25 kg/m(2)), and the prevalence of elevated A1C was also analyzed according to BMI. RESULTS: One-third (31.2%) of the patients with PCOS had elevated A1C. The prevalence of elevated A1C (≥5.7%) was similar in obese women with PCOS and obese controls (23.5 and 20.0%, respectively, P= 1.0) but non-obese women with PCOS (mean age 29.8 ± 5.3 years) had a higher prevalence of elevated A1C than non-obese controls (31.2 versus 6.6%, respectively, P< 0.001). Logistic regression analysis of all subjects showed that the odds that a woman has elevated A1C was 6.7 times higher if she has PCOS (adjusted odds ratio 6.67, 95% confidence interval 3.50-12.70). CONCLUSIONS: The high prevalence of elevated A1C in non-obese patients with PCOS and an increased risk of elevated A1C associated with PCOS suggest that PCOS itself may be associated with abnormal A1C status. Assessing A1C level in young, non-obese patients with PCOS may be a useful new approach to screening for diabetes.
Assuntos
Hemoglobinas Glicadas/metabolismo , Síndrome do Ovário Policístico/metabolismo , Adolescente , Adulto , Glicemia , Estudos de Casos e Controles , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/metabolismo , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/metabolismo , Feminino , Humanos , Síndrome do Ovário Policístico/complicações , Prevalência , Fatores de RiscoRESUMO
OBJECTIVES: Since it has been suggested that intracytoplasmic sperm injection (ICSI) might impair the early development of embryos and twin pregnancies have physiologically different aspects from singleton pregnancies, we aimed to investigate the effect of ICSI on the human chrionic gonadotropin (hCG) levels in twin pregnancies. METHODS: A total of 220 clinical pregnancies which underwent controlled ovarian hyperstimulation and in vitro fertilization/ICSI were analyzed retrospectively. RESULTS: In twin pregnancies, the mean number of retrieved oocytes and estradiol (E2) levels on hCG day were significantly higher in ICSI group in spite of lower dose of gonadotropin. The hCG levels according to insemination method did not demonstrate any difference after adjustment for age of patient and partner, BMI, treatment regimens, serum E2 on hCG day, number of oocytes retrieved and date of sampling. CONCLUSIONS: The hCG values according to fertilization methods were not significantly different both in twin pregnancies with adjustment for confounders.