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1.
Rev Assoc Med Bras (1992) ; 67(4): 590-596, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34495066

RESUMO

OBJECTIVE: Polycystic ovary syndrome can be divided into different subtypes, including insulin resistance and hyperandrogenism. The aim of this study was to investigate the relationship between serum asprosin levels and polycystic ovary syndrome subtypes. METHODS: A total of 93 women with polycystic ovary syndrome and 77 healthy women as controls were selected for this study. The clinical and laboratory data were compared between the Polycystic ovary syndrome group and the control group. The Polycystic ovary syndrome group was further divided into subgroups: (1) women with or without hyperandrogenism (polycystic ovary syndrome hyperandrogenism and Polycystic ovary syndrome none-hyperandrogenism, respectively) and (2) women with or without insulin resistance (polycystic ovary syndrome insulin resistance and Polycystic ovary syndrome none-insulin resistance, respectively). Serum asprosin was measured by using enenzyme-linked immunosorbent assay. RESULTS: Serum asprosin levels showed no significant difference between the polycystic ovary syndrome and control groups. However, it was significantly lower in the Polycystic ovary syndrome HA and insulin resistance groups compared with the respective Polycystic ovary syndrome none-hyperandrogenism and none-insulin resistance groups (p<0.05). In the Polycystic ovary syndrome group, serum asprosin was negatively correlated with body mass index, luteinizing hormone, testosterone, basal antral follicles, fasting insulin, homeostatic model assessment of insulin resistance, and triglycerides. After adjusting for body mass index, the correlations were not significant, and asprosin was only positively correlated with prolactin (prolactin; r=0.426, p<0.001). CONCLUSION: Our study shows that women with polycystic ovary syndrome hyperandrogenism or insulin resistance exhibit significantly lower serum asprosin levels compared with controls, and the lower asprosin level directly correlated with prolactin level.


Assuntos
Hiperandrogenismo , Resistência à Insulina , Hormônios Peptídicos , Síndrome do Ovário Policístico , Índice de Massa Corporal , Estudos Transversais , Feminino , Fibrilina-1 , Humanos , Insulina , Proteínas dos Microfilamentos , Fragmentos de Peptídeos , Síndrome do Ovário Policístico/complicações , Testosterona
2.
J Steroid Biochem Mol Biol ; 214: 105991, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34487832

RESUMO

BACKGROUND: Valproate (VPA) is an antiepileptic drug (AEDs) with an ideal effect against epilepsy as well as other neuropsychiatric diseases. There is considerable evidence that women taking VPA are prone to reproductive endocrine disorders. However, few studies have been published about VPA effects on human ovarian granulosa cells. METHODS: By treating human ovarian granulosa cell line KGN with VPA, the cell viability and progesterone production function were evaluated. RNA-sequencing was applied to uncover the global gene expression upon VPA treatment. RESULTS: We revealed that VPA dose-dependently repressed the viability of KGN. VPA treatment at 600 µM inhibited the progesterone production. The mRNA and protein expression of CYP11A1 and STAR, two key enzymes in the biosynthesis of progesterone, were both suppressed. Gene set enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis of the transcriptome revealed classical functions of VPA as a neuromodulator and regulator of histone acetylation modifications. In addition to this, VPA commonly affected many steroid metabolism related genes in follicle cells, such as promoting the expression of vitamin D receptor (VDR). CONCLUSION: Our findings suggest that VPA caused steroids metabolism pathways disturbance related with ovarian function and inhibited progesterone biosynthesis by inhibiting the expression of steroidogenesis genes. Our research may provide theoretical basis for the better use of VPA and the possible ways to counteract its side effects.

3.
Oxid Med Cell Longev ; 2021: 6668365, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367465

RESUMO

Oxidative stress has been recognized as one of the causal mediators of female infertility by affecting the oocyte quality and early embryo development. Improving oxidative stress is essential for reproductive health. Melatonin, a self-secreted antioxidant, has a wide range of effects by improving mitochondrial function and reducing the damage of reactive oxygen species (ROS). This minireview illustrates the applications of melatonin in reproduction from four aspects: physiological ovarian aging, vitrification freezing, in vitro maturation (IVM), and oxidative stress homeostasis imbalance associated with polycystic ovary syndrome (PCOS), emphasising the role of melatonin in improving the quality of oocytes in assisted reproduction and other adverse conditions.

6.
Acta Obstet Gynecol Scand ; 100(6): 1116-1123, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33616957

RESUMO

INTRODUCTION: Frozen embryo transfer is associated with a higher rate of live birth and a lower risk for ovarian hyperstimulation syndrome in women with polycystic ovary syndrome (PCOS) compared with fresh embryo transfer. The aim of this study is to assess the optimal endometrial preparation protocol for women with PCOS undergoing frozen embryo transfer. MATERIAL AND METHODS: We conducted a historical cohort analysis of 1720 women with PCOS who underwent the "freeze-all" strategy between August 2014 and August 2017 because of their high risk for ovarian hyperstimulation syndrome. Three endometrial preparation protocols were used: natural cycle (NC; n = 191), which relies on the dominant follicle to secrete estrogen that then promotes endometrial growth; ovarian stimulation (OS; n = 96), which induces follicle growth using low doses of human menopausal gonadotropin; and hormone replacement (HRT; n = 1433), which uses exogenous estradiol to promote endometrial growth. The primary outcome was live birth. RESULTS: For women who received a single embryo transfer, the live birth rates for the NC, OS, and HRT groups were 62.4%, 65.0%, and 52.2%, respectively. The live birth rate in the HRT group was significantly lower than that seen in the OS and NC groups (P = .009). The clinical pregnancy rates of the three groups were 72.3%, 73.8%, and 64.9%, respectively; this difference did not reach statistical significance (P = .071). CONCLUSIONS: The rate of live birth with the NC and OS regimens was higher than with the HRT protocol in women with PCOS who undergo single-blastocyst frozen embryo transfer.


Assuntos
Coeficiente de Natalidade , Criopreservação/métodos , Transferência Embrionária/métodos , Fertilização In Vitro/métodos , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/terapia , Adulto , Estudos de Coortes , Feminino , Humanos , Infertilidade Feminina/etiologia , Infertilidade Feminina/terapia , Síndrome do Ovário Policístico/complicações , Gravidez , Taxa de Gravidez
7.
Int J Mol Sci ; 22(2)2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33430468

RESUMO

Alterations in miRNAs are associated with many metabolic disorders, such as type 2 diabetes (T2DM). The miR-23b/27b/24-1 cluster contains miR-23b, miR-27b, and miR-24-1, which are located within 881 bp on chromosome 9. Studies examining the roles of miR-23b, miR-27b, and miR-24-1 have demonstrated their multifaceted functions in variable metabolic disorders. However, their joint roles in metabolism in vivo remain elusive. To investigate this subject, we constructed miR-23b/27b/24-1 cluster knockout (KO) mice. Compared with wild-type (WT) mice, the KO mice exhibited impaired glucose tolerance, which was accompanied by a reduction in the respiratory exchange rate (RER). These alterations were more noticeable after a high-fat diet (HFD) induction. Hepatic metabolomic results showed decreased expression of reduced nicotinamide adenine dinucleotide (NADH), nicotinamide adenine dinucleotide (NAD), phosphoenolpyruvic acid (PEP), and phosphoric acid, which are involved in the glycolysis pathway. The transcriptomic results indicated that genes involved in glycolysis showed a downregulation trend. qPCR and Western blot revealed that pyruvate kinase (PKLR), the key rate-limiting enzyme in glycolysis, was significantly reduced after the deletion of the miR-23b/27b/24-1 cluster. Together, these observations suggest that the miR-23b/27b/24-1 cluster is involved in the regulation of glucose homeostasis via the glycolysis pathway.


Assuntos
Diabetes Mellitus Tipo 2/genética , Intolerância à Glucose/genética , Glucose/genética , MicroRNAs/genética , Animais , Diabetes Mellitus Tipo 2/patologia , Glucose/metabolismo , Glicólise/genética , Humanos , Camundongos , Camundongos Knockout , Família Multigênica/genética , NAD/metabolismo , Taxa Respiratória/genética , Transdução de Sinais/genética
8.
Endocrine ; 72(1): 287-293, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33169290

RESUMO

PURPOSE: Anti-Müllerian hormone (AMH) is crucial for folliculogenesis. Prenatal exposure to AMH in mice produces a phenocopy of polycystic ovary syndrome (PCOS) in the adult female offspring. The aim of this study was to determine whether genetic variation in AMH gene contribute to PCOS in women of Chinese ancestry. METHODS: We conducted a case-control genetic study in 383 PCOS case and 433 control women of Chinese ancestry. The exons and the 5' flanking region of AMH were sanger sequenced. Bioinformatic prediction of variant deleteriousness was performed. RESULTS: Seven novel heterozygous variants along with 15 rare known variants in AMH were identified in women with PCOS but not in controls. The novel variants included one frameshift variant (c.125_129delACTTG), one synonymous variant (c.1095C>T), one variant (c.-14T>C) in the 5'-untranslated region (UTR), four variants(c.-775C>T, c.-682C>T, c.-333A>G, c.-137A>T) in 5' flanking sequence. Of all the AMH variants identified in women with PCOS, eight were predicted to be deleterious by bioinformatic analysis. The PCOS carriers of predicted-to-be-deleterious PCOS-specific AMH variants had increased total follicle numbers compared to PCOS noncarriers (p = 0.021). CONCLUSIONS: Our findings suggest the AMH plays a role in the development of PCOS. The exact mechanisms by which the predicted-to-be-deleterious novel and rare AMH variants described in our study affect AMH function requires further study.

9.
J Assist Reprod Genet ; 38(2): 471-477, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33216309

RESUMO

PURPOSE: Elevated oxidative stress has been proposed as an important factor in the pathogenesis of polycystic ovary syndrome (PCOS)-related infertility. Our study was aimed at simultaneously exploring local and systemic oxidative stress in PCOS individuals and its relationship with embryo quality. METHODS: We recruited 86 PCOS cases and 60 controls. Five representative oxidative stress markers, namely, total oxidant capacity (TOC), total antioxidant capacity (TAC), malonaldehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD), were measured in both follicular fluid (FF) and serum. RESULTS: Women with PCOS compared to normal controls had higher levels of TOC in both FF (10.13 ± 2.68 vs.7.03 ± 2.45, P < 0.001) and serum (11.76 ± 2.92 vs. 8.82 ± 2.57, P < 0.001). The oxidative stress index (OSI, the ratio of TOC to TAC) was also higher in PCOS cases. They were still significant after BMI adjustment (Padj<0.01). In addition, the serum OSI level was much higher than the FF OSI level in both groups. Correlation analysis showed that the FF and serum TOC were negatively correlated with the high-quality embryo rate on day 3 and the later blastocyst formation rate in the PCOS group (P < 0.05). The correlation coefficient was higher in FF. Moreover, as the regression analysis data showed, the FF MDA level was significantly associated with embryo quality indicators (P < 0.05). CONCLUSIONS: PCOS was accompanied by elevated oxidative stress in both serum and FF. Even though serum oxidative stress was severe, the study suggested that FF oxidative stress contributed more to embryo quality, to which we should give more attention in the future.

10.
Biochem Biophys Res Commun ; 532(3): 336-340, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-32873390

RESUMO

Golgi matrix protein 130 (GM130), encoded by GOLGA2, is the classical marker of the Golgi apparatus. It plays important roles in various mitotic events, such as interacting with importin-alpha and liberating spindle assembly factor TPX2 to regulate mitotic spindle formation. A previous study showed that in vitro knockdown of GM130 could regulate the meiotic spindle pole assembly. In the current study, we found that knockout (KO) mice progressively died, had a small body size and were completely infertile. Furthermore, we constructed an oocyte-specific GM130 knockout mouse model (GM130-ooKO) driven by Gdf9-Cre. Through breeding assays, we found that the GM130-ooKO mice showed similar fecundity as control mice. During superovulation assays, the KO and GM130-ooKO mice had comparable numbers of ovulated eggs, oocyte maturation rates and normal polar bodies, similar to the control groups. Thus, this study indicated that deletion of GM130 might have a limited impact on the maturation and morphology of oocytes. This might due to more than one golgin sharing the same function, with others compensating for the loss of GM130.


Assuntos
Desenvolvimento Embrionário/fisiologia , Meiose/fisiologia , Proteínas de Membrana/deficiência , Oócitos/citologia , Oócitos/fisiologia , Animais , Autoantígenos/genética , Autoantígenos/fisiologia , Desenvolvimento Embrionário/genética , Feminino , Fertilidade/genética , Fertilidade/fisiologia , Complexo de Golgi/fisiologia , Transtornos do Crescimento/genética , Transtornos do Crescimento/fisiopatologia , Infertilidade Feminina/genética , Infertilidade Feminina/fisiopatologia , Masculino , Meiose/genética , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , Camundongos , Camundongos Knockout , Oogênese/genética , Oogênese/fisiologia , Ovulação/genética , Ovulação/fisiologia , Gravidez
11.
Reprod Biomed Online ; 41(4): 724-728, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32773339

RESUMO

RESEARCH QUESTION: This study investigated whether rs1784692 is a risk factor for polycystic ovary syndrome (PCOS) in Han Chinese women. DESIGN: A case-control study was conducted in Han Chinese women, involving 526 PCOS patients and 522 control participants. A TaqMan MGB probe assay was used to genotype the variant rs1784692. Dominant and additive models were employed for genotype-phenotype association analysis in the PCOS and control samples. RESULTS: The minor allele C of rs1784692 is protective against PCOS (odds ratio [OR] 0.556, 95% confidence interval [CI] 0.408-0.759, P = 1.83 × 10-4), even after adjustment for body mass index (BMI) and age (ORadj 0.539, 95% CI 0.391-0.743, Padj= 1.62 × 10-4). Genotype-phenotype analysis of the dominant model showed that mean BMI in the CC+CT group was higher than in the TT group in the PCOS group (27.12 ± 5.82 versus 24.57 ± 4.52, P = 1.0 × 10-3), but not in the control groups, indicating that the minor allele C of rs1784692 associates with BMI in women with PCOS. The mean LH (luteinizing hormone) concentration in the CC+CT group was lower than in the TT group in PCOS and control participants (9.33 ± 5.08 versus 10.93 ± 5.91, P = 0.036; 4.39 ± 1.66 versus 4.89 ± 2.07, P = 0.021). Genotype-phenotype analysis of additive model showed that mean BMI in TC group was higher than in the TT group in PCOS patients compared with control participants (27.14 ± 5.81 versus 24.57 ± 4.52, P = 3.06 × 10-3). CONCLUSIONS: The SNP rs1784692 in gene ZBTB16 is protective against PCOS but is associated with increased BMI in Han Chinese women with PCOS.

12.
Reprod Biomed Online ; 41(3): 395-401, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32600942

RESUMO

RESEARCH QUESTION: Is there a difference in live birth rate between a freeze-only strategy and fresh embryo transfer, and what is the effect of varying progesterone concentrations on the day of human chorionic gonadotrophin (HCG) administration? DESIGN: A secondary analysis of data from three randomized trials comparing the live birth rate after elective frozen versus fresh embryo transfer, which respectively enrolled 1508 women with polycystic ovary syndrome, 2157 ovulatory women who underwent cleavage-stage embryo transfer and 1650 ovulatory women who underwent single blastocyst transfer. Women were randomly assigned to the frozen or fresh embryo transfer group in the original trials. The primary outcome was live birth rate after the initial embryo transfer. RESULTS: The live birth rate after a freeze-only strategy was consistently higher than fresh embryo transfer at any progesterone concentration on the day of HCG administration. Nonetheless, the between-group difference in live birth rate after frozen versus fresh embryo transfer was greater in women with progesterone concentrations ≥1.14 ng/ml (52.7% versus 37.3%, odds ratio (OR) 1.88, 95% confidence interval (CI) 1.55-2.27, P = 7.89 â€¯×  10-11) than in women with progesterone concentrations <1.14 ng/ml (53.3% versus 48.1%, OR 1.23, 95% CI 1.08-1.41, P = 0.002). In women with progesterone concentration ≥1.14 ng/ml, frozen embryo transfer also resulted in higher rates of conception and clinical pregnancy than fresh embryo transfer. CONCLUSION: In women with normal or high ovarian response, a freeze-only strategy resulted in a higher live birth rate than fresh embryo transfer, irrespective of progesterone concentration. Moreover, women with progesterone concentration ≥1.14 ng/ml may benefit more from a freeze-only strategy.

13.
Hum Reprod ; 35(7): 1711-1718, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32619219

RESUMO

STUDY QUESTION: Does the inheritance of polycystic ovary syndrome (PCOS) susceptibility single-nucleotide polymorphism affect the phenotype of offspring? SUMMARY ANSWER: Male offspring who inherit PCOS-related genetic variations from PCOS mothers were more susceptible to developing the metabolic abnormality in their later life. WHAT IS KNOWN ALREADY: Genetic factors are considered the major etiology of PCOS. Previous studies have highlighted that offspring of women with PCOS had an increased risk of the same disease or PCOS-like symptoms. STUDY DESIGN, SIZE, DURATION: The study involved 172 children born to women with PCOS and 529 children born to non-PCOS women. All offspring were conceived by assisted reproductive technologies. PARTICIPANTS/MATERIALS, SETTING, METHODS: The offspring ranged from 1 to 8 years old. Metabolic phenotype analyses were performed in offspring aged from 2 to 8 (N = 619). Sanger sequencing, TaqMan and Sequenom MassARRAY were used to sequence the samples. MAIN RESULTS AND THE ROLE OF CHANCE: In male offspring, the fasting insulin (FINS) (P = 0.037) homeostasis model assessment of insulin resistance (HOMA-IR) (P = 0.038) and the homeostasis model assessment of pancreatic beta-cell function (HOMA-ß) (P = 0.038) levels were higher in offspring of PCOS mothers compared to controls. In female offspring, PCOS offspring had a significantly higher anti-Müllerian hormone levels (P = 0.001) compared to those from control mothers. In male offspring of PCOS mothers, subjects with a T allele at rs2349415 in the gene FSHR had higher FINS (P = 0.023), HOMA-IR (P = 0.030) and HOMA-ß levels (P = 0.013) than those in the homozygous CC group. The same increased trend in FINS, HOMA-IR and HOMA-ß levels could be found in the CC and TC group in rs2268361 located in gene FSHR compared to the TT group (P = 0.029, P = 0.030, P = 0.046, respectively). As for rs10818854 in the DENND1A gene, the AA and AG group had a higher FINS (P = 0.037) and HOMA-ß (P = 0.008) levels than the homozygous CC group. LIMITATIONS, REASONS FOR CAUTION: Firstly, the offspring may be too young to see any phenotype changes. Secondly, this study only analyzed the differences of genotype frequency using the dominant model instead of all three models due to the limited sample size of the homozygous model. The results, therefore, should be replicated and performed in a larger sample size population. Thirdly, environmental impacts cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS: The findings presented in this thesis add to our understanding the changes in offspring born to PCOS women and remind us to consider early intervention to avoid more severe effects. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China 2017YFC1001000 (to Z.-J.C.), the National Natural Science Foundation of China 81430029 (to Z.-J.C.), 81622021 and 31571548 (to H.Z.), the National Natural Science Foundation of Shandong Province JQ201816 (to H.Z.) and Shandong Provincial Key Research and Development Program 2017G006036 (to L.-L.C.) and 2018YFJH0504 (to Z.-J.C.). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Síndrome do Ovário Policístico , Criança , Pré-Escolar , China , Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte , Feminino , Fatores de Troca do Nucleotídeo Guanina , Humanos , Lactente , Masculino , Nucleotídeos , Fenótipo , Síndrome do Ovário Policístico/genética , Polimorfismo de Nucleotídeo Único
14.
Sci Rep ; 10(1): 8993, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32488141

RESUMO

PURPOSE: Polycystic ovarian morphology (PCOM) is one of the key features of polycystic ovary syndrome (PCOS). The diagnosis of PCOM according to the Rotterdam criteria (≥12 antral follicles per ovary) is debated because of the high prevalence of PCOM in the general population. Androgen receptor (AR) is associated with the PCOS phenotype and might as well play a role during folliculogenesis. This study is aimed to investigate the expression of the AR in PCOS granulosa cells (GCs) and its relationship with the PCOM phenotype. METHODS: 106 PCOS cases and 63 controls were included from the Center for Reproductive Medicine, Shandong University. The diagnosis of PCOS was following the Rotterdam criteria (2003). Total RNA was extracted from GCs retrieved from ovarian stimulation. The expression of AR was amplified by means of quantitative real-time polymerase chain reaction. RESULTS: The AR expression was significantly decreased in PCOS cases, especially in the tPCOM subgroup (≥20 antral follicles per ovary). Correlation analyses showed that AR expression was significantly correlated with serum FSH levels in controls and non-tPCOM. In the tPCOM subgroup, the AR expression was significantly correlated with serum LH levels. Interestingly, the significance of these correlations gradually disappeared as the threshold of antral follicles increased above 24 for PCOM. CONCLUSIONS: AR was differently expressed in PCOS and especially in the tPCOM subtype. The correlation of AR expression with serum FSH and LH might be associated with the number of follicles in PCOM.


Assuntos
Células da Granulosa/fisiologia , Síndrome do Ovário Policístico/etiologia , Receptores Androgênicos/genética , Adulto , Estudos de Casos e Controles , Feminino , Hormônio Foliculoestimulante/sangue , Expressão Gênica , Células da Granulosa/patologia , Humanos , Hormônio Luteinizante/sangue , Ovário , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Adulto Jovem
15.
Artigo em Inglês | MEDLINE | ID: mdl-32425888

RESUMO

Polycystic ovary syndrome is characterized by reproductive and metabolic disturbances throughout the female lifespan. Therefore, this study aimed to determine whether genome-wide association studies (GWAS)-identified risk variants for PCOS could confer risk of metabolic syndrome (MS) or insulin resistance (IR). Fifteen independent SNPs mapping to 11 GWAS loci genotyped in a total of 2,082 Han Chinese women independent of previous GWAS and phenotype-genotype correlations were assessed. The CC group for rs12478601 in THADA was associated with decreased rate of MS after adjustment for age (23.2 vs. 27%, P = 0.042, OR = 0.81). Using a dominant model, the GG+AG group for rs2059807 in INSR was associated with increased risk of MS after adjustment for age (26.8 vs. 22.5%, P = 0.023, OR = 1.27). The GG + GT group for rs4784165 in TOX3 was found to be associated with an increased rate of IR after adjustment for age and BMI(53.3 vs. 48.5%, P = 0.027, OR = 1.27). The GG+AG group for rs2479106 in DENND1A was associated with a decreased rate of IR (48.3 vs. 53.6%, adjusted P = 0.039, OR = 0.80). After exclusion of PCOS cases with a family history of diabetes, hypertension, or dyslipidemia, the phenotype-genotype correlations between the genes INSR and TOX3 and MS or IR were still significant (P < 0.05). Three SNPs (rs13429458 in THADA, rs10818854 in DENND1A, and rs2059807 in INSR) were significantly associated with IR; however, their association was not significant after adjustment for age and BMI. This genotype-phenotype study thus provides clues that THADA, INSR, TOX3, and DENND1A play a role in PCOS possibly through a metabolic disorder-related pathway.


Assuntos
Antígenos CD/genética , Proteínas Reguladoras de Apoptose/genética , Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Resistência à Insulina , Síndrome Metabólica/diagnóstico , Proteínas de Neoplasias/genética , Síndrome do Ovário Policístico/complicações , Polimorfismo de Nucleotídeo Único , Receptor de Insulina/genética , Transativadores/genética , Adulto , Biomarcadores/análise , Feminino , Seguimentos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Síndrome Metabólica/etiologia , Síndrome Metabólica/patologia , Prognóstico
16.
Sci China Life Sci ; 63(6): 849-865, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32291558

RESUMO

The number of growth factors involved in female fertility has been extensively studied, but reluctance to add essential growth factors in culture media has limited progress in optimizing embryonic growth and implantation outcomes, a situation that has ultimately led to reduced pregnancy outcomes. Insulin-like growth factor II (IGF-II) is the most intricately regulated of all known reproduction-related growth factors characterized to date, and is perhaps the predominant growth factor in human ovarian follicles. This review aims to concisely summarize what is known about the role of IGF-II in follicular development, oocyte maturation, embryonic development, implantation success, placentation, fetal growth, and in reducing placental cell apoptosis, as well as present strategies that use growth factors in culture systems to improve the developmental potential of oocytes and embryos in different species. Synthesizing the present knowledge about the physiological roles of IGF-II in follicular development, oocyte maturation, and early embryonic development should, on the one hand, deepen our overall understanding of the potential beneficial effects of growth factors in female reproduction and on the other hand support development (optimization) of improved outcomes for assisted reproductive technologies.


Assuntos
Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/fisiologia , Reprodução/fisiologia , Animais , Desenvolvimento Embrionário/fisiologia , Feminino , Desenvolvimento Fetal/fisiologia , Regulação da Expressão Gênica , Humanos , Oócitos/fisiologia , Folículo Ovariano/fisiologia , Gravidez
17.
Front Endocrinol (Lausanne) ; 11: 615846, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33716953

RESUMO

Background: Women who undergo chronic exposure to excessive estrogen are at a high risk of developing breast cancer. TOX3 has been reported to be highly expressed in breast tumors and is closely related to estrogen receptors. However, the effect of TOX3 on estrogen synthesis remains poorly understood. Methods: Using lentiviruses as a vector, we stably overexpressed TOX3 in the ovarian granulosa cell line KGN, the cells where estradiol is primarily produced, to investigate its role in estrogen production as well as cell viability and apoptosis. RNA-Sequencing was applied to uncover the global gene expression upon TOX3 overexpression. Results: We observed an increased level of cell viability and a reduced cell apoptosis rate after TOX3 overexpression, and the level of estradiol in the cell culture supernatant also increased significantly. Gene set enrichment analysis of the transcriptome showed that the ovarian steroidogenesis pathway was significantly enriched. Similarly, pathway mapping using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses also showed that TOX3 overexpression affects the ovarian steroidogenesis pathway. Further experiments showed that upregulated FSHR, CYP19A1, and BMP6 accounted for the enhanced estrogen synthesis. Conclusion: Our study demonstrated that TOX3 quantitatively and qualitatively stimulates estrogen synthesis by enhancing estrogen signaling pathway-related gene expression in ovarian granulosa cells. These findings suggest that TOX3 may play a vital role in the pathogenesis of breast cancer.


Assuntos
Proteínas Reguladoras de Apoptose/biossíntese , Estrogênios/biossíntese , Redes Reguladoras de Genes/fisiologia , Células da Granulosa/metabolismo , Análise de Sequência de RNA/métodos , Transativadores/biossíntese , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular Tumoral , Estrogênios/genética , Feminino , Humanos , Ovário/metabolismo , Transativadores/genética
18.
Reprod Biol ; 19(4): 368-373, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31753743

RESUMO

MiR-125b regulates the kinds of cells that undergo apoptosis physiologically and pathologically. However, whether miR-125b affects the apoptotic behavior of trophoblasts and the underlying molecular regulatory mechanisms remains unclear. This study investigated the effect of miR-125b on apoptosis of HTR-8/SVneo cells in vitro. Constructed wild-type reporter vector (Wt-3'UTR) or mutated type reporter vector (Mut-3'UTR) reporter plasmids were transiently transfected into 293 T cells along with miR-125b mimics or a negative control. The luciferase reporter assay was used to validate whether the predicted MCL1 gene is a direct target of miR-125b. The HTR8/SVneo cells were transfected with miR-125 mimics, inhibitors, or a scramble control. Real-time polymerase chain reaction and western blotting were used to analyze mRNA and protein expression of the target gene MCL1. Flow cytometry was used to determine the effects on apoptosis. The luciferase activity assay validated the ability of miR-125b to specifically attenuate MCL1 transcription in the 293 T cell line, suggesting that MCL1 is a direct target of miR-125b. After transfection by miR-125b, relative expression and translation of the target gene MCL1 mRNA were repressed in HTR-8/SVneo cells. Trophoblast cells were induced to undergo apoptosis by overexpressing miR-125b in the HTR-8/SVneo cell line. In conclusion, MiR-125b may induced apoptosis of HTR8/SVneo cells by targeting MCL1. Our findings suggest that miR-125b may play a pivotal role in the pathophysiology of placentation.


Assuntos
Apoptose , MicroRNAs/fisiologia , Proteína de Sequência 1 de Leucemia de Células Mieloides/fisiologia , Trofoblastos/fisiologia , Linhagem Celular , Humanos
19.
Reprod Biomed Online ; 39(6): 969-975, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31680064

RESUMO

RESEARCH QUESTION: What are the factors associated with the increased incidence of pre-eclampsia in pregnancies conceived through IVF using autologous oocytes? DESIGN: A nested case-control study from the combined cohort of three multicentre randomized trials comparing fresh to frozen embryo transfer, including women who achieved clinical pregnancy after the first embryo transfer. Multivariable logistic regression was used to assess the effect of baseline characteristics, ovarian response parameters, type of fertilization, type of embryo transfer, and number of gestational sacs on the risk of pre-eclampsia. RESULTS: There were 2965 clinical pregnancies and 90 women were diagnosed with pre-eclampsia. Twin gestations (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.50-3.66), mean arterial pressure (OR 1.04, 95% CI 1.01-1.07), frozen embryo transfer (OR 2.06, 95% CI 1.27-3.35), body mass index (BMI) (OR 1.10, 95% CI 1.02-1.18), progesterone level on the day of human chorionic gonadotrophin trigger (OR 1.53, 95% CI 1.07-2.20), and the total dose of gonadotrophin (OR 0.999, 95% CI 0.999-1.000, P = 0.037) were associated with the risk of pre-eclampsia. When the analysis was confined to women who underwent frozen embryo transfer, twin gestations (OR 2.44, 95% CI 1.43-4.18), BMI (OR 1.13, 95% CI 1.03-1.23) and the total dose of gonadotrophin (OR 0.999, 95% CI 0.999-1.000, P = 0.014) were still related to the risk of pre-eclampsia. The embryo stage at transfer was not included in the final models. CONCLUSIONS: Frozen embryo transfer was an independent risk factor of pre-eclampsia in assisted reproductive technology. The high ovarian response may also increase the risk of pre-eclampsia. The embryo stage at transfer was not related to the risk of pre-eclampsia.


Assuntos
Transferência Embrionária/efeitos adversos , Indução da Ovulação/efeitos adversos , Pré-Eclâmpsia/epidemiologia , Adulto , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Pré-Eclâmpsia/etiologia , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
20.
Reprod Biol Endocrinol ; 17(1): 68, 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31421682

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic disorders characterized by hyperandrogenism, polycystic ovaries and ovulatory dysfunction. Several studies have reported that the aberrant expression of miRNAs contributes a lot to disordered folliculogenesis in PCOS, though the role and underlying mechanism of microRNA-200b (miR-200b) and microRNA-200c (miR-200c) in the development of PCOS remain unclear. METHODS: The expression of miR-200b in granulosa cells (GCs) derived from 90 PCOS patients and 70 controls was analyzed by using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Granulosa-like tumor cell line (KGN) was cultured for cell counting kit-8 (CCK-8) assays after over-expression of miR-200b, miR-200c or knockdown phosphatase and tensin homolog (PTEN). TargetScan was used to identify the potential targets of miR-200b and miR-200c, which was further verified by qRT-PCR, western blot and luciferase assays. RESULTS: Significantly increased expression of miR-200b was observed in PCOS patients compared with the controls. Moreover, over-expression of miR-200b and miR-200c inhibited the proliferation of KGN cells. In addition, our results verified that miR-200b and miR-200c directly targeted PTEN, knockdown of which suppressed KGN cells proliferation. CONCLUSION: Our findings demonstrate that miR-200b and miR-200c suppress the proliferation of KGN cells by targeting PTEN, and this might provide new evidence for abnormal proliferation of GCs in PCOS.


Assuntos
Proliferação de Células/genética , Células da Granulosa/metabolismo , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , Síndrome do Ovário Policístico/genética , Regulação para Cima , Adulto , Linhagem Celular Tumoral , Feminino , Células da Granulosa/patologia , Humanos , PTEN Fosfo-Hidrolase/metabolismo , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/metabolismo , Interferência de RNA , Transdução de Sinais/genética
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