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1.
Mol Med Rep ; 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31702034

RESUMO

Under physiological conditions, human ovarian granulosa cells (GCs), are responsible for a number of processes associated with folliculogenesis and oogenesis. The primary functions of GCs in the individual phases of follicle growth are: Hormone production in response to follicle stimulating hormone (FSH), induction of ovarian follicle atresia through specific molecular markers and production of nexus cellular connections for communication with the oocyte. In recent years, interest in obtaining stem cells from particular tissues, including the ovary, has increased. Special attention has been paid to the novel properties of GCs during long­term in vitro culture. It has been demonstrated that the usually recycled material in the form of follicular fluid can be a source of cells with stem­like properties. The study group consisted of patients enrolled in the in vitro fertilization procedure. Total RNA was isolated from GCs at 4 time points (after 1, 7, 15 and 30 days of culture) and was used for microarray expression analysis (Affymetrix® Human HgU 219 Array). The expression of 22,480 transcripts was examined. The selection of significantly altered genes was based on a P­value <0.05 and expression higher than two­fold. The leucine rich repeat containing 17, collagen type I α1 chain, bone morphogenetic protein 4, twist family bHLH transcription factor 1, insulin like growth factor binding protein 5, GLI family zinc finger 2 and collagen triple helix repeat containing genes exhibited the highest changes in expression. Reverse­transcription­quantitative PCR was performed to validate the results obtained in the analysis of expression microarrays. The direction of expression changes was validated in the majority of cases. The presented results indicated that GCs have the potential of cells that can differentiate towards osteoblasts in long­term in vitro culture conditions. Increased expression of genes associated with the osteogenesis process suggests a potential for uninduced change of GC properties towards the osteoblast phenotype. The present study, therefore, suggests that GCs may become an excellent starting material in obtaining stable osteoblast cultures. GCs differentiated towards osteoblasts may be used in regenerative and reconstructive medicine in the future.

2.
DNA Cell Biol ; 38(6): 549-560, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31120353

RESUMO

Proper course of folliculogenesis and oogenesis have an enormous impact on female fertility. Both processes take place in the ovary and involve not only the maturing germ cell, but also few types of somatic cells that assist the ovarian processes and mediate the dialog with the oocyte. These cells, granulosa and theca, are heavily involved in essential reproductive processes, such as ovulation, fertilization, and embryo implantation. In this study, we have used the expressive microarray approach to analyze the transcriptome of porcine granulosa cells, during short-term in vitro culture. We have further selected differentially expressed gene ontologies, involved in cell proliferation, migration, adhesion, and tissue development, namely, "cell-cell adhesion," "cell motility," "cell proliferation," "tissue development," and "tissue migration" to screen them for the possibility of discovery of new markers of those processes. A total of 303 genes, expression of which varied significantly in different culture periods and belonged to the analyzed ontology groups, were detected, of which 15 that varied the most (between 0 and 48 h of culture) were selected for validation. As the validation confirmed the transcriptomic patterns, 10 genes of biggest changes in expression (CAV1, IGFBP5, ITGB3, FN1, ITGA2, LAMB1, POSTN, FAM83D, KIF14, and CDK1) were analyzed, described, and referred to the context of the study, with the most promising new markers and further proof for the viability of the currently recognized ones detailed. Overall, the study provided valuable insight into the molecular functioning of in vitro granulosa cell cultures.


Assuntos
Adesão Celular/genética , Movimento Celular/genética , Proliferação de Células/genética , Células da Granulosa/metabolismo , Animais , Biomarcadores/metabolismo , Células Cultivadas , Feminino , Perfilação da Expressão Gênica , Células da Granulosa/citologia , Células da Granulosa/fisiologia , Análise de Sequência com Séries de Oligonucleotídeos , Suínos
3.
Int J Mol Sci ; 20(9)2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067669

RESUMO

This paper aims to identify and describe new genetic markers involved in the processes of protein expression and modification reflected in the change of mitochondrial activity before and after in vitro maturation of the oocyte. Porcine oocytes collected from the ovaries of slaughtered landrace gilts were subjected to the process of in vitro maturation. Transcriptomic changes in the expression profile of oocyte genes involved in response to hypoxia, the transmembrane protein receptor serine threonine kinase signaling pathway, the "transforming growth factor ß receptor signaling pathway", "response to protein stimulus", and "response to organic substance" were investigated using microarrays. The expression values of these genes in oocytes was analyzed before (immature) and after (mature) in vitro maturation, with significant differences found. All the significantly altered genes showed downregulation after the maturation process. The most changed genes from these gene ontologies, FOS, ID2, VEGFA, BTG2, CYR61, ESR1, AR, TACR3, CCND2, CHRDL1, were chosen to be further validated, described and related to the literature. Additionally, the mitochondrial activity of the analyzed oocytes was measured using specific dyes. We found that the mitochondrial activity was higher before the maturation process. The analysis of these results and the available literature provides a novel insight on the processes that occur during in vitro oocyte maturation. While this knowledge may prove to be useful in further research of the procedures commonly associated with in vitro fertilization procedures, it serves mostly as a basic reference for further proteomic, in vivo, and clinical studies that are necessary to translate it into practical applications.


Assuntos
Mitocôndrias/metabolismo , Oócitos/metabolismo , Oogênese/genética , Transcriptoma , Animais , Hipóxia Celular/genética , Células Cultivadas , Feminino , Técnicas de Maturação in Vitro de Oócitos , Mitocôndrias/genética , Oócitos/citologia , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais , Suínos , Fator de Crescimento Transformador beta/metabolismo
4.
Ginekol Pol ; 90(3): 115-121, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949999

RESUMO

O: BJECTIVES: Copeptin has been reported to play an important role in metabolic response in women with PCOS. However, the optimal cut-off value for detecting subjects with insulin resistance (IR) remains undetermined. We investigated whether copeptin can serve as an indicator of IR and tried to determine the optimal cut-off value of plasma copeptin concentration in detecting subjects with PCOS and IR. MATERIAL AND METHODS: We carried out a case-control study on 158 women with PCOS and HOMA-IR < 2.5, 96 women with PCOS with HOMA-IR ≥ 2.5, and 70 healthy volunteers. Plasma copeptin, as well as hormonal, biochemical, metabolic, and IR parameters, were measured. To investigate whether copeptin allows IR to be predicted in PCOS, we used logistic regression models and ROC curve analysis. RESULTS: Median plasma copeptin concentration was the highest in the women with PCOS and HOMA-IR ≥ 2.5. Logistic regression analysis revealed that copeptin was the strongest predictor of HOMA ≥ 2.5 (OR: 53.34 CI 7.94-358.23, p < 0.01). Analysis of ROC curves indicated that the cut-off value above 4 pmol/L of plasma copeptin concentration had high (99%) specificity but very low (21%) sensitivity in diagnosing of IR (AUC 0.607 (95% CI 0.53-0.68. CONCLUSIONS: Our findings suggest that copeptin is associated with IR in PCOS patients, but due to low sensitivity should not be considered as a marker of IR.

5.
Ginekol Pol ; 90(3): 154-160, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30950005

RESUMO

OBJECTIVES: An attempt was made to demonstrate the superiority of the treatment model using continuous subcutaneous insulin infusion (CSII) over multiple daily injections (MDI) of insulin in achieving a successful pregnancy outcome and good newborn's condition in patients with type 1 diabetes. MATERIAL AND METHODS: The study included 297 infants born to type 1 diabetic patients; 175 patients were treated with MDI and 122 with CSII. Maternal metabolic control during pregnancy, gestational weight gain, insulin requirements, pregnancy outcome and neonatal status were compared between MDI and CSII arm. The composite adverse neonatal outcome was diagnosed if at least one of the following was found: abnormal birth weight (LGA or SGA), congenital malformation, miscarriage, intrauterine fetal death, emergency CS due to fetal risk, iatrogenic prematurity, RDS, hypoglycemia, hyperbilirubinemia, and the postpartum pH in the umbilical artery ≤ 7.1. RESULTS: The studied groups did not differ regarding gestational week at delivery, a proportion of births at full term, preterm births, miscarriages, or late pregnancy losses (intrauterine fetal death > 22 weeks). Newborns of mothers treated with CSII showed lower incidence of neonatal complications (composite adverse neonatal outcome) compared to those of mothers treated with MDI (60% vs 74%, respectively; p = 0.01). We did not find any association between the mode of treatment and composite adverse maternal outcome. CONCLUSIONS: The use of CSII in the treatment of pregnant women with type 1 diabetes was associated with reduced number of neonatal complications presented as neonatal composite outcome but had no influence on maternal outcome.

6.
Biomed Res Int ; 2019: 6545210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30834271

RESUMO

The physiological processes that drive the development of ovarian follicle, as well as the process of oogenesis, are quite well known. Granulosa cells are major players in this occurrence, being the somatic element of the female gamete development. They participate directly in the processes of oogenesis, building the cumulus-oocyte complex surrounding the ovum. In addition to that, they have a further impact on the reproductive processes, being a place of steroid sex hormone synthesis and secretion. It is known that the follicle development creates a major need for angiogenesis and blood vessel development in the ovary. In this study, we use novel molecular approaches to analyze markers of these processes in porcine granulosa cultured primarily in vitro. The cells were recovered from mature sus scrofa specimen after slaughter. They were then subjected to enzymatic digestion and culture primarily for a short term. The RNA was extracted from cultures in specific time periods (0h, 24h, 48h, 96h, and 144h) and analyzed using expression microarrays. The genes that exhibited fold change bigger than |2|, and adjusted p-value lower than 0.05, were considered differentially expressed. From these, we have chosen the members of "angiogenesis," "blood vessel development," "blood vessel morphogenesis," "cardiovascular system development," and "vasculature development" for further selection. CCL2, FGFR2, SFRP2, PDPN, DCN, CAV1, CHI3L1, ITGB3, FN1, and LOX which are upregulated, as well as CXCL10, NEBL, IHH, TGFBR3, SCUBE1, IGF1, EDNRA, RHOB, PPARD, and SLITRK5 genes whose expression is downregulated through the time of culture, were chosen as the potential markers, as their expression varied the most during the time of culture. The fold changes were further validated with RT-qPCR. The genes were described, with special attention to their possible function in GCs during culture. The results broaden the general knowledge about GC's in vitro molecular processes and might serve as a point of reference for further in vivo and clinical studies.


Assuntos
Vasos Sanguíneos/crescimento & desenvolvimento , Células da Granulosa/citologia , Neovascularização Fisiológica/genética , Folículo Ovariano/crescimento & desenvolvimento , Animais , Vasos Sanguíneos/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento/genética , Células da Granulosa/metabolismo , Humanos , Morfogênese/genética , Oócitos/crescimento & desenvolvimento , Oogênese/genética , Ovário/crescimento & desenvolvimento , Ovário/metabolismo , Cultura Primária de Células , Biossíntese de Proteínas/genética , Suínos
7.
Mol Med Rep ; 19(3): 1705-1715, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30628715

RESUMO

Granulosa cells (GCs) have many functions in the endocrine system. Most notably, they produce progesterone following ovulation. However, it has recently been proven that GCs can change their properties when subjected to long­term culture. In the present study, GCs were collected from hyper­stimulated ovarian follicles during in vitro fertilization procedures. They were grown in vitro, in a long­term manner. RNA was collected following 1, 7, 15 and 30 days of culture. Expression microarrays were used for analysis, which allowed to identify groups of genes characteristic for particular cellular processes. In addition, reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was performed to validate the obtained results. Two ontological groups characteristic for processes associated with the development and morphogenesis of the heart were identified during the analyses: 'Heart development' and 'heart morphogenesis'. The results of the microarrays revealed that the highest change in expression was demonstrated by the lysyl Oxidase, oxytocin receptor, nexilin F­actin binding protein, and cysteine­rich protein 3 genes. The lowest change was exhibited by odd­skipped related transcription factor 1, plakophilin 2, transcription growth factor­ß receptor 1, and kinesin family member 3A. The direction of changes was confirmed by RT­qPCR results. In the present study, it was suggested that GCs may have the potential to differentiate towards other cell types under long­term in vitro culture conditions. Thus, genes belonging to the presented ontological groups can be considered as novel markers of proliferation and differentiation of GCs towards the heart muscle cells.


Assuntos
Técnicas de Cultura de Células , Diferenciação Celular/genética , Linhagem da Célula/genética , Folículo Ovariano/citologia , Células Cultivadas , Feminino , Células da Granulosa/citologia , Células da Granulosa/metabolismo , Humanos , Morfogênese/genética , Folículo Ovariano/metabolismo , Ovulação/genética , Progesterona/genética , Proteína-Lisina 6-Oxidase/genética , Receptores de Ocitocina/genética
8.
Int J Mol Sci ; 20(1)2018 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-30587792

RESUMO

The growth and development of oocyte affect the functional activities of the surrounding somatic cells. These cells are regulated by various types of hormones, proteins, metabolites, and regulatory molecules through gap communication, ultimately leading to the development and maturation of oocytes. The close association between somatic cells and oocytes, which together form the cumulus-oocyte complexes (COCs), and their bi-directional communication are crucial for the acquisition of developmental competences by the oocyte. In this study, oocytes were extracted from the ovaries obtained from crossbred landrace gilts and subjected to in vitro maturation. RNA isolated from those oocytes was used for the subsequent microarray analysis. The data obtained shows, for the first time, variable levels of gene expression (fold changes higher than |2| and adjusted p-value < 0.05) belonging to four ontological groups: regulation of cell proliferation (GO:0042127), regulation of cell migration (GO:0030334), and regulation of programmed cell death (GO:0043067) that can be used together as proliferation, migration or apoptosis markers. We have identified several genes of porcine oocytes (ID2, VEGFA, BTG2, ESR1, CCND2, EDNRA, ANGPTL4, TGFBR3, GJA1, LAMA2, KIT, TPM1, VCP, GRID2, MEF2C, RPS3A, PLD1, BTG3, CD47, MITF), whose expression after in vitro maturation (IVM) is downregulated with different degrees. Our results may be helpful in further elucidating the molecular basis and functional significance of a number of gene markers associated with the processes of migration, proliferation and angiogenesis occurring in COCs.


Assuntos
Apoptose/genética , Proliferação de Células/genética , Oócitos/metabolismo , Transcriptoma , Animais , Movimento Celular/genética , Células do Cúmulo/metabolismo , Células do Cúmulo/patologia , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Técnicas de Maturação in Vitro de Oócitos , Análise de Sequência com Séries de Oligonucleotídeos , Oócitos/crescimento & desenvolvimento , Oócitos/patologia , RNA/genética , RNA/metabolismo , Suínos , Regulação para Cima
9.
Histochem Cell Biol ; 2018 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-30382374

RESUMO

The human ovarian granulosa cells (GCs) surround the oocyte and form the proper architecture of the ovarian follicle. The ability of GCs to proliferate and differentiate in the conditions of in vitro culture has been proven. However, there is still a large field for extensive investigation of molecular basics, as well as marker genes, responsible for these processes. This study aimed to find the new marker genes, encoding proteins that regulate human GCs in vitro capability for proliferation and differentiation during long-term primary culture. The human follicular GCs were collected from hyper-stimulated ovarian follicles during IVF procedures and transferred to a long-term in vitro culture. The culture lasted for 30 days, with RNA samples isolated at days 1, 7, 15, 30. Transcriptomic analysis was then performed with the use of Affymetrix microarray. Obtained results were then subjected to bioinformatical evaluation and sorting. After subjecting the datasets to KEGG analysis, three differentially expressed ontology groups "cell differentiation" (GO:0030154), "cell proliferation" (GO:0008283) and "cell-cell junction organization" (GO:0045216) were chosen for further investigation. All three of those ontology groups are involved in human GCs' in vitro lifespan, proliferation potential, and survival capability. Changes in expression of genes of interest belonging to the chosen GOs were validated with the use of RT-qPCR. In this manuscript, we suggest that VCL, PARVA, FZD2, NCS1, and COL5A1 may be recognized as new markers of GC in vitro differentiation, while KAT2B may be a new marker of their proliferation. Additionally, SKI, GLI2, FERMT2, and CDH2 could also be involved in GC in vitro proliferation and differentiation processes. We demonstrated that, in long-term in vitro culture, GCs exhibit markers that suggest their ability to differentiate into different cells types. Therefore, the higher expression profile of these genes may also be associated with the induction of cellular differentiation processes that take place beyond the long-term primary in vitro culture.

10.
Theriogenology ; 121: 122-133, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30145542

RESUMO

The processes underlying maturation of mammalian oocytes are considered crucial for the oocytes ability to undergo monospermic fertilization. The same factors of influence are suggested to impact the development of sex associated characteristics, allowing sex differentiation to progress during embryonic growth. The primary aim of the study was to analyze the gene ontology groups involved in regulation of porcine oocytes' response to endogenous stimuli. The results obtained would indicate potential genes influencing sex differentiation. Additionally, they could help to determine new genetic markers, expression profile of which is substantially regulated during porcine oocytes' in vitro maturation. To achieve that, porcine oocytes were collected for analysis before and after in vitro maturation. Pigs were used as they are a readily available model that presents significant similarity to humans in terms of physiology and anatomy. Microarray analysis of oocytes, before and after in vitro maturation was performed and later validated by RT-qPCR. We have particularly detected and analyzed genes belonging to gene ontology groups associated with hormonal stimulation during maturation of the oocytes, that exhibited significant change in expression (fold change ≥ |2|; p < 0.05) namely "Female sex differentiation" (CCND2, MMP14, VEGFA, FST, INHBA, NR5A1), "Response to endogenous stimulus" (INSR, ESR1, CCND2, TXNIP, TACR3, MMP14, FOS, AR, EGR2, IGFBP7, TGFBR3, BTG2, PLD1, PHIP, UBE2B) and "Response to estrogen stimulus" (INSR, ESR1, CCND2, IHH, TXNIP, TACR3, MMP14). Some of them were characteristic for just one of the described ontologies, while some belonged into multiple ontological terms. The genes were analyzed, with their relation to the processes of interest explained. Overall, the study provides us with a range of genes that might serve as molecular markers of in vitro maturation associated processes of the oocytes. This knowledge might serve as a reference for further studies and, after further validation, as a potentially useful knowledge in assessment of the oocytes during assisted reproduction processes.

11.
Ginekol Pol ; 89(2): 74-79, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29512811

RESUMO

OBJECTIVES: Preconception counseling, maternal health-related habits, diet, folic acid consumption, substances abuse, may all impact the outcome of pregnancy. The aim of this study was to compare the planning and preparation for pregnancy among pregnant women with and without infertility. MATERIAL AND METHODS: A survey of health behaviors prior to and during pregnancy that could affect pregnancy outcomes, including laboratory tests performed, stimulant usage, initiation of prenatal care, and folic acid intake, was conducted among 400 pregnant women. The study group included 121 women (30.25%) diagnosed with prior infertility, while the control group included 279 women (69.74%) who did not report any problems conceiving. RESULTS: All patients (100%) from the study group and 70,97% from the control group planned their pregnancy(p < 0.0001). Patients in the study group performed significantly more laboratory tests prior to pregnancy, including: complete blood count, urine analysis, fasting blood glucose concentration, testing for toxoplasmosis, and Pap smear, compared with the control group (p < 0.0001). There was no difference between groups regarding the knowledge of when and why folic acid supplementation is required (p > 0.05). CONCLUSIONS: Effective education of women, regarding pregnancy planning and behaviours, that may impact pregnancy outcome is still a serious challange to public health in Poland. Our study indicates that reaching general population with the education is most important to achieve best results in preconceptional care.


Assuntos
Comportamentos Relacionados com a Saúde , Infertilidade , Cuidado Pré-Concepcional/estatística & dados numéricos , Adolescente , Adulto , Consumo de Bebidas Alcoólicas , Técnicas de Laboratório Clínico/estatística & dados numéricos , Serviços de Planejamento Familiar/estatística & dados numéricos , Feminino , Ácido Fólico/uso terapêutico , Humanos , Infertilidade/psicologia , Gravidez , Fumar , Adulto Jovem
12.
Int J Mol Sci ; 18(12)2017 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-29232835

RESUMO

Because of the deep involvement of granulosa cells in the processes surrounding the cycles of menstruation and reproduction, there is a great need for a deeper understanding of the ways in which they function during the various stages of those cycles. One of the main ways in which the granulosa cells influence the numerous sex associated processes is hormonal interaction. Expression of steroid sex hormones influences a range of both primary and secondary sexual characteristics, as well as regulate the processes of oogenesis, folliculogenesis, ovulation, and pregnancy. Understanding of the exact molecular mechanisms underlying those processes could not only provide us with deep insight into the regulation of the reproductive cycle, but also create new clinical advantages in detection and treatment of various diseases associated with sex hormone abnormalities. We have used the microarray approach validated by RT-qPCR, to analyze the patterns of gene expression in primary cultures of human granulosa cells at days 1, 7, 15, and 30 of said cultures. We have especially focused on genes belonging to ontology groups associated with steroid biosynthesis and metabolism, namely "Regulation of steroid biosynthesis process" and "Regulation of steroid metabolic process". Eleven genes have been chosen, as they exhibited major change under a culture condition. Out of those, ten genes, namely STAR, SCAP, POR, SREBF1, GFI1, SEC14L2, STARD4, INSIG1, DHCR7, and IL1B, belong to both groups. Patterns of expression of those genes were analyzed, along with brief description of their functions. That analysis helped us achieve a better understanding of the exact molecular processes underlying steroid biosynthesis and metabolism in human granulosa cells.


Assuntos
Técnicas de Cultura de Células/métodos , Perfilação da Expressão Gênica/métodos , Células da Granulosa/citologia , Redes e Vias Metabólicas , Esteroides/biossíntese , Células Cultivadas , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Células da Granulosa/metabolismo , Humanos , Análise de Sequência com Séries de Oligonucleotídeos
13.
Mol Med Rep ; 14(6): 5401-5407, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27840997

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. A number of PCOS complications may be associated with the elevated level of angiotensin II and low bradykinin concentrations. The aim of the present study was to investigate the frequencies of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms in women with PCOS and to determine the association between ACE genetic variants and the risk of metabolic and cardiovascular complications in such women. A total of 138 PCOS patients and 110 healthy volunteers were enrolled. Cardiovascular risk was estimated according to the criteria of the American Heart Association and Androgen Excess and PCOS Society. The median average age was 28.5 (26.0­31.0) and 27.0 (24.0­30.0) years in the control and PCOS groups, respectively (P=0.004). Anthropometric parameters, including body mass index and waist circumference were significantly higher in the PCOS patients. In the PCOS group, 97 (57.4%) of the subjects were metabolically unhealthy, whereas, in the control group 51 (46.4%) subjects were (P=0.07). The II, ID, and DD genotypes frequencies were 29.1, 44.5, and 26.4% in the controls and 5.0, 37.7, and 57.3% in the PCOS patients. The cardioprotective I allele was observed significantly less frequently in the women with PCOS compared with the controls [odds ratio (OR), 3.27; P=0.0001]. The DD genotype, which is known to increase cardiovascular risk, was more frequently observed in PCOS patients (OR, 3.87; P=0.0003), whereas the cardioprotective II genotype occurred in this group less frequently (OR, 0.4; P=0.06). The results of the present study demonstrated a statistically significant association between the ACE I/D polymorphism and the presence and intensity of metabolic disturbances in women with PCOS.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Mutação INDEL , Peptidil Dipeptidase A/genética , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Polimorfismo Genético , Adulto , Alelos , Biomarcadores , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Razão de Chances , Fatores de Risco , Adulto Jovem
14.
Ginekol Pol ; 87(4): 246-53, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27321094

RESUMO

INTRODUCTION: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. PCOS is characterized by anovulation, polycystic ovaries, hyperandrogenism leading to infertility, dermatological and psychological problems, as well as the risk of developing Metabolic Syndrome (MetS) and cardiovascular disease (CVD). The exact cause of PCOS remains unclear. Various biochemical and genetic markers have been implicated in predisposition to PCOS, but no single variant has been associated with the syndrome. Some authors connect hyperhomocysteinemia (HHcy) with MetS and its components. The MTHFR gene C677T polymorphism is a common genetic abnormality leading to hyperhomocysteinemia. OBJECTIVES: The aim of the study was to confirm the existence of a possible correlation between metabolic disturbances in PCOS and the MTHFR C677T polymorphism. MATERIAL AND METHODS: A total of 98 patients diagnosed with PCOS according to the Rotterdam criteria and 101 age-matched healthy controls were included in the study. Genotyping of MTHFR C677T was performed by the real time PCR method. RESULTS: Statistically significant differences were observed between those two groups with regard to body mass index (BMI), waist circumference (WC), hip circumference (HC), fasting insulin, total cholesterol (TC), and triglycerides (TG). No significant differences in the prevalence of the genotypes of the MTHFR C677T gene polymorphism were found between the PCOS group and controls. Despite the lack of significant differences, we observed a tendency for a higher prevalence of the TT genotype in the PCOS group (p = 0.06). No statistically significant differences were observed between the PCOS group and the control group in terms of the presence of the MetS components and the predisposition to develop MetS. CONCLUSIONS: Our study did not confirm an association between the MTHFR C677T gene polymorphism and the development of MetS in PCOS. Further studies with larger sample size might be useful to determine this association.


Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Síndrome do Ovário Policístico/genética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Adulto , Feminino , Frequência do Gene , Genótipo , Humanos , Adulto Jovem
16.
Mol Med Rep ; 13(5): 4437-42, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27035733

RESUMO

Single nucleotide polymorphisms (SNPs) in the growth differentiation factor (GDF)­9 gene are associated with premature ovarian failure, insufficient ovarian stimulation and a poor in vitro fertilization (IVF) score in women with diminished ovarian reserve. The aim of the present study was to assess the effect of C447T (rs254286) and G546A (rs10491279) SNPs on ovary stimulation response, oocyte quality, fertilization rate and outcome of clinical pregnancy in an infertile population of Polish females (n=86) treated with IVF. The present study also included a group of fertile women (n=202). The P­trend value, calculated for the GDF­9 C447T transition in infertile women, was statistically significant and were equal to 0.0195. A significant association of the GDF­9 C447T SNP was observed with infertility for the C/C vs. T/T + C/T model (OR= 2.140; 95% CI=1.043­4.393; P=0.0349). The GDF­9 G546A SNP was significantly associated with the G/A vs. G/G model with poor ovarian stimulation (OR=9.303; 95% CI=2.568­33.745; P=0.0008) and poor fertilization rate (OR=2.981; 95% CI=1.033­8.607; P=0.0385). For the GDF­9 C447T SNP, a significant association was observed between the C/C + C/T vs. T/T model and a poor ovarian stimulation response (OR=15.309; 95% CI=0.875­267.83; P=0.0078), and a poor fertilization rate (OR=4.842; 95% CI=1.310­17.901; P=0.0121). The present genetic evaluation revealed associations between IVF outcomes and the GDF­9 A546G and C447T SNPs. Additionally, these results indicated that the GDF­9 C447T SNP is a possible candidate genetic risk factor for female infertility in the Polish population.


Assuntos
Fertilização In Vitro , Fator 9 de Diferenciação de Crescimento/genética , Infertilidade Feminina/genética , Polimorfismo de Nucleotídeo Único , Adulto , Feminino , Humanos , Infertilidade Feminina/epidemiologia , Polônia/epidemiologia , Gravidez
17.
Ginekol Pol ; 86(4): 300-4, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26117990

RESUMO

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. It is manifested by hyperandrogenism, polycystic ovaries on ultrasound, oligomenorrhoea and anovulation. PCOS patients are more vulnerable to metabolic disorders: insulin resistance, obesity endothelium dysfunction, atherosclerosis, and activation of proinflammatory factors. This association shows that PCOS might be an ovarian manifestation of a metabolic syndrome. Insulin resistance is also strongly correlated with reproductive failure. Approximately 100 factors, secreted in adipose tissue, are responsible for its regulation. Adipocytokines have been found to play an important role in regulating insulin sensitivity Abnormal levels of adipokines are detected in patients with insulin resistance. Studies indicate that these factors, and their different activity in PCOS women, may affect changes observed in their metabolism and, especially may participate in the development of insulin resistance. There are several adipokines whose role has been thoroughly investigated and many that we still know very little about, for example apein and visfatin. Counseling PCOS patients about the possibility of developing metabolic syndrome, diabetes mellitus, and cardiovascular diseases should be a standard of care.


Assuntos
Adipocinas/metabolismo , Insulina/metabolismo , Síndrome do Ovário Policístico/metabolismo , Saúde da Mulher , Tecido Adiposo/metabolismo , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Metabolismo dos Lipídeos , Síndrome do Ovário Policístico/complicações
18.
Ginekol Pol ; 86(11): 840-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26817316

RESUMO

OBJECTIVES: Polycystic ovary syndrome (PCOS) is a common endocrinopathy in premenopausal women, associated with risk of metabolic syndrome and cardiovascular disease (CVD). CVD risk evaluation is recommended for PCOS patients. This study aimed to evaluate the risk of CVD in PCOS patients and to identify the best predictors for metabolic and cardiovascular disturbances. MATERIAL AND METHODS: The study included 169 PCOS patients and 110 healthy women in reproductive age. We estimated cardiovascular risk according to American Heart Association and Androgen Excess-PCOS Society criteria that classified patients as metabolically unhealthy (MU) or metabolically healthy (MH). RESULTS: The PCOS group had significantly higher body mass index (BMI), waist circumference, and waist-to-hip ratio (P < 0.000001). Metabolic syndrome was only defined among PCOS patients (8.9%). No obesity was observed in the control group. Waist circumference ≥ 80 cm was presented in 44% of PCOS patients in comparison to 14.5% of control participants (P < 0.000001). There was a significant tendency for higher fasting insulin levels in the PCOS population (P < 0.00001). Surprisingly the PCOS-MH group had the highest high-density lipoprotein (HDL) levels. ROC curves were used to indicate parameters diagnosing metabolically unhealthy women and revealed that WC, BMI and HC seem to be the strongest predictors of metabolic disturbances in PCOS but in the healthy population in reproductive age biochemical findings such as low HDL or increased fasting glycemia presented stronger predictive value than patients' anthropometric features. CONCLUSIONS: Physicians need to remember to adopt different diagnostic approach while seeking metabolic complications in these different groups of women.


Assuntos
Doenças Cardiovasculares/etiologia , Síndrome Metabólica/etiologia , Obesidade/etiologia , Síndrome do Ovário Policístico/complicações , Adulto , Índice de Massa Corporal , Doenças Cardiovasculares/metabolismo , Colesterol/sangue , Feminino , Humanos , Síndrome Metabólica/metabolismo , Obesidade/metabolismo , Polônia , Fatores de Risco , Saúde da Mulher , Adulto Jovem
19.
Aust N Z J Obstet Gynaecol ; 53(2): 130-5, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23316799

RESUMO

AIMS: The aim was to evaluate the outcome of pregnancies with type 1 diabetes (T1DM) treated from the first trimester with continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). METHODS: In a retrospective, observational study, we matched 64 CSII patients for age, age at onset and duration of diabetes and HbA1c in the first trimester with 64 MDI pregnancies. We analysed carbohydrate metabolism, insulin requirements, development of PIH, progression of retinopathy and fetal outcome. RESULTS: In CSII group, we found a significantly smaller insulin requirement both at the beginning of pregnancy and before delivery, significant decrease in HbA1c levels and significantly smaller number of hypoglycaemic episodes in the second trimester and significantly more hyperglycaemic episodes in the first trimester. In both groups, maternal, fetal and perinatal outcomes were similar and the number of hypo- and hyperglycaemic episodes decreased throughout pregnancy. CONCLUSION: Continuous subcutaneous insulin infusion (CSII) treatment in pregnant women with type 1 diabetes is associated with a reduced number of hypoglycaemia and decreased insulin requirement. We noted no difference in perinatal outcome comparing women on multiple insulin injections with those on continuous insulin infusion.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hiperglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Gravidez em Diabéticas/tratamento farmacológico , Adulto , Análise de Variância , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hiperglicemia/etiologia , Infusões Subcutâneas , Injeções Subcutâneas , Gravidez , Gravidez em Diabéticas/sangue , Estudos Retrospectivos , Adulto Jovem
20.
Ginekol Pol ; 83(2): 104-10, 2012 Feb.
Artigo em Polonês | MEDLINE | ID: mdl-22568354

RESUMO

OBJECTIVES: The aim of the study was to assess the outcome of pregnancies after in vitro fertilization protocol (IVF), that were complicated by the ovarian hyperstimulation syndrome (OHSS). MATERIAL AND METHODS: We examined 26 women undergoing IVF due to OHSS. Patients were divided into two groups: with early OHSS and late OHSS. All women were screened for age, Body Mass Index (BMI), number of embryos transferred, OHSS symptoms and duration of hospitalization. Pregnancy outcome was assessed by rate of miscarriages, premature deliveries and multiple gestations. We assessed also the delivery mode, birth weight of all newborns and obstetric complications. RESULTS: Early OHSS occurred in 10 patients and late OHSS complicated the pregnancies of 16 women. 94.1% of the late OHSS cases occurred in cycles with pregnancy. The miscarriage rate was 26.9%. 38.5% of all births were premature and 26.9% of the newborns had low birth weight. Multiple pregnancies were confirmed in 46.2% of the patients, triplets mainly in women with late OHSS. No fetal anomalies were diagnosed. The most common antenatal complications were: diabetes mellitus, cholestasis and intrauterine infection. The rate of the cesarean sections was 73.8%. CONCLUSIONS: OHSS is a risk factor for miscarriage, preterm delivery multiple gestation, obstetric complications and cesarean section. Late OHSS may be closely associated with the conception cycles.


Assuntos
Fertilização In Vitro/métodos , Síndrome de Hiperestimulação Ovariana/epidemiologia , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Adulto , Comorbidade , Feminino , Humanos , Recém-Nascido , Indução da Ovulação/métodos , Assistência Perinatal/métodos , Polônia , Gravidez , Gravidez Múltipla/estatística & dados numéricos , Nascimento Prematuro/epidemiologia , Saúde da Mulher , Adulto Jovem
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