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1.
J Hum Reprod Sci ; 14(4): 356-364, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35197680

RESUMO

BACKGROUND: Limited information is available on the aetiology and semen profiles of male infertility in Indian population. AIM: The aim of this study is to study the clinical and semen characteristics of men attending the infertility clinic and also to understand the impact of World Health Organization (WHO) 2010 reference values on the diagnosis of male infertility. SETTING AND DESIGN: A retrospective study evaluating the medical case records (January 2005 to December 2015, [n = 1906]) of men attending infertility clinic in Mumbai, India. MATERIALS AND METHODS: The aetiology was classified based on the andrology evaluation and other investigations. Semen profiles were compared during the years 2005-2010 and 2011-2015 using WHO 1999 and WHO 2010 criteria, respectively. STATISTICAL ANALYSIS: The Chi-square and Mann-Whitney U tests were performed using Open Source Epidemiological software and Social science calculators. RESULTS: The aetiology of male infertility was determined in 62% of the men; while the cause remained undetermined in 38%. Varicocele (25%), urogenital infections (10%), sexual dysfunctions (8%) and vas aplasia (8%) were identified as major aetiologies in our cohort. Men with sexual dysfunctions and vas aplasia were significantly higher during the years 2011-2015 as compared to 2005-2010. Men having normozoospermia (10%) and azoospermia (3%) were increased, whereas those having oligoasthenozoospermia (17%) were reduced in 2011-2015 as compared to 2005-2010. According to WHO 1999 criteria , 12-15% of men showed abnormal semen profiles. The semen parameters of these men became normal on using WHO 2010 reference values. CONCLUSIONS: Varicocele is the most common aetiology in infertile men. Idiopathic infertility was seen in a higher proportion among the infertile men.

2.
Gene ; 577(2): 180-6, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26625974

RESUMO

BACKGROUND: Insulin-like factor 3 (INSL3), secreted by the ovarian theca cells is involved in androgen production, follicular growth and oocyte maturation. Both androgens and INSL3 levels are reported to be elevated in women with polycystic ovary syndrome (PCOS), indicating that INSL3 could contribute to PCOS etiology. This case-control association study explored the impact of INSL3 polymorphisms on PCOS susceptibility and its related traits. METHODS: Genotyping of exonic polymorphisms of INSL3 was performed in controls (n=333) and PCOS (n=405) women. Phenotyping (clinical, biochemical and hormonal parameters) was carried out in 205 controls and 301 PCOS women. Genotype, haplotype and genotype-phenotype associations were determined using statistical tests. RESULTS: Three polymorphisms in exon 1-rs2286663 (G/A), rs1047233 (A/G), and rs6523 (A/G), and one in exon 3-rs1003887 (G/A), were present in our study subjects. The frequencies of rs6523 and AGAG haplotype were significantly increased in PCOS women. The rs6523 polymorphism showed significant association with increased cholesterol and HDL-C levels in PCOS women while in controls with decreased FBS, Bio-T and FAI, and increased SHBG levels. Significant association of, rs1047233 polymorphism with improved androgen related parameters in controls, rs2286663 polymorphism with decreased QUICKI in PCOS and rs1003887 polymorphism with increased insulin levels and HOMA-IR in controls were observed. CONCLUSIONS: The rs6523 polymorphism and AGAG haplotype of INSL3 showed significant association with increased risk of PCOS. Additionally, INSL3 polymorphisms influenced metabolic and hyperandrogenemia related parameters in both controls and PCOS women. This is the first study to suggest that INSL3 may be a genetic predisposition factor in PCOS pathophysiology.


Assuntos
Haplótipos , Insulina/genética , Síndrome do Ovário Policístico/genética , Polimorfismo de Nucleotídeo Único , Proteínas/genética , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Índia
3.
J Assist Reprod Genet ; 30(7): 913-21, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23748472

RESUMO

PURPOSE: Peroxisome proliferator activated receptor gamma (PPARγ), a transcription factor involved in glucose and lipid metabolism is one of the candidate genes associated with polycystic ovary syndrome (PCOS). We investigated individual and combined associations of Pro12Ala and His447His polymorphisms of PPARγ with PCOS susceptibility and its related traits (hyperinsulinemia, hyperandrogenemia and lipid parameters) in Indian women. METHOD: Genotyping of PPARγ polymorphisms in this case-control study was performed in PCOS (n = 450) and age-matched controls (n = 300) by direct sequencing. Clinical, anthropometric, hormonal and metabolic parameters were estimated in 275 women with PCOS and 169 controls. Chi-square test was used to compare the categorical data while regression analysis was used to evaluate association of genotypes with PCOS as well as its related phenotypes. RESULTS: The frequencies of CC and CG + GG genotypes of Pro12Ala (χ² = 15.3, p < 0.0001) and CC and CT + TT genotypes of His447His (χ² = 12.7, p = 0.0004) polymorphisms were significantly different between PCOS and controls. Logistic regression analysis revealed a significant association of PCOS with Pro12Ala but not the His447His polymorphism. Carriers of variant genotypes at both PPARγ loci showed significantly reduced 2 h glucose levels while carriers of variant His447His genotype showed lower fasting insulin and HOMA-IR levels in PCOS women. CONCLUSIONS: Pro12Ala polymorphism of PPARγ showed significant association with decreased PCOS susceptibility. Both polymorphisms influenced insulin related traits (2 h glucose, fasting insulin and HOMA-IR) and improved glucose metabolism in these women. This is the first report to establish that variations in PPARγ gene influence the insulin resistance pathophysiology in Indian women with PCOS.


Assuntos
Hiperandrogenismo/genética , Resistência à Insulina/genética , PPAR gama/genética , Síndrome do Ovário Policístico/genética , Adolescente , Adulto , Feminino , Frequência do Gene , Predisposição Genética para Doença , Variação Genética , Genótipo , Glucose/metabolismo , Humanos , Índia , Insulina/sangue , Polimorfismo de Nucleotídeo Único , Adulto Jovem
4.
Gynecol Endocrinol ; 26(12): 874-82, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20500101

RESUMO

Obesity and hyperandrogenaemia are key features of polycystic ovary syndrome (PCOS). The aim of this study was to investigate whether leptin and androgens are associated with obesity in PCOS subjects and identify whether there exist any genetic alterations in leptin gene in women with PCOS. The results reveal that leptin levels are elevated in women with PCOS and associate with BMI. However, irrespective of the obesity status leptin levels are higher in PCOS cases indicating that increased BMI/obesity may not be the only factor contributing to elevated levels of leptin. With regard to testosterone and androstenedione, the levels were increased in obese individuals irrespective of PCOS status. No correlation between leptin and androstenedione or testosterone was observed in controls and PCOS subjects. The single-nucleotide polymorphism G19A detected in the untranslated exon 1 of leptin gene was not associated with PCOS and does not contribute to elevated levels of leptin. The results overall suggest that androgen and leptin levels are increased in PCOS and obesity. It demonstrates that obesity is a confounding factor for hyperandrogenaemia irrespective of their PCOS status. The study rules out role of obesity status and leptin genotype in increase in leptin levels observed in PCOS cases.


Assuntos
Androstenodiona/sangue , Leptina/sangue , Obesidade/sangue , Síndrome do Ovário Policístico/sangue , Testosterona/sangue , Adulto , DNA/química , DNA/genética , Feminino , Genótipo , Humanos , Leptina/genética , Modelos Lineares , Obesidade/genética , Síndrome do Ovário Policístico/genética , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA
5.
J Assist Reprod Genet ; 27(6): 317-26, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20237833

RESUMO

PURPOSE: This retrospective study was designed to analyze the FSHR gene variants in subjects with primary and secondary amenorrhea with hypergonadotropic hypogonadism. MATERIALS AND METHODS: Eighty six women with primary or secondary amenorrhea and 100 normally cycling proven fertile women of Indian origin were retrospectively studied. These subjects were systematically screened for entire FSHR gene. RESULTS: The frequency distribution of polymorphism at -29 position of FSHR gene is altered in women with primary and secondary amenorrhea as compared to controls. AA genotype at -29 position of FSHR gene seems to be associated with increased serum FSH levels in the study subjects. We have identified a novel homozygous mutation C(1723)T (Ala(575)Val) in one woman with primary amenorrhea. CONCLUSIONS: Our findings suggest that increased serum FSH levels in subjects with primary amenorrhea correlated to FSHR genotype at position -29. We identified a novel homozygous mutation C(1723)T (Ala(575)Val) in a woman with primary amenorrhea.


Assuntos
Amenorreia/genética , Polimorfismo Genético , Receptores do FSH/genética , Amenorreia/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Haplótipos , Humanos , Polimorfismo de Fragmento de Restrição , Estudos Retrospectivos
6.
Hum Reprod ; 24(12): 3230-5, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19684044

RESUMO

BACKGROUND: Premature ovarian failure (POF) is a disorder characterized by lack of ovulation and elevated serum gonadotrophin levels before the age of 40 years. The cause of POF in most cases is unknown. As mice lacking the Androgen receptor (Ar) gene reportedly have a POF-like phenotype, we hypothesize that, variations in the AR gene maybe one of the causative factors for POF in humans. Thus the objective of the study is to evaluate the number of CAG repeats in exon 1 of the AR gene in non-familial, non-syndromic cases of POF. METHODS: A clinic-based case-control study. Seventy-eight patients with non-familial, non-syndromic POF, and 90 controls were recruited to investigate the CAG repeat numbers in exon 1 of the AR gene by PCR and Gene Scan analysis. RESULTS: The mean CAG repeat length in exon 1 of the AR gene of women with POF was 23.6 +/- 3.8, which was significantly higher than controls (20.08 +/- 3.45) (P < 0.001). The biallelic mean CAG repeat ranged from 11 to 32 in the control women, compared to 16 to 30 in the POF patients. The 22 CAG repeat allele followed by the 24 CAG repeat allele was found to be at highest frequency (15.38 and 12.8%) in POF cases, although the 19 CAG repeat allele was observed at highest frequency (12.2%) in controls. CONCLUSIONS: The observation suggests that the CAG repeat length is increased in women with POF as compared with controls, and may be pathogenic for POF, at least in a subset of Indian women.


Assuntos
Insuficiência Ovariana Primária/genética , Receptores Androgênicos/genética , Repetições de Trinucleotídeos/genética , Adulto , Alelos , Estudos de Casos e Controles , Éxons , Feminino , Humanos , Índia , Reação em Cadeia da Polimerase
7.
Reprod Biomed Online ; 19(2): 281-6, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19712568

RESUMO

The CGG repeat stretch in the FMR1 gene is polymorphic, ranging from 5 to 50 repeats in the normal population. Expansion of the repeats to the premutation range (50-200) has been associated with premature ovarian failure (POF). This case-control study was conducted to enumerate CGG repeats in the FMR1 gene in 80 Indian women with non-familial, non-syndromic POF, and 70 controls from the same ethnicity. A possible association between CGG repeats and endocrine profile of these cases was investigated. All patients and controls had CGG repeats in the normal polymorphic range. Serum FSH concentrations were significantly raised in both POF cases and controls having CGG repeats in the 31-40 repeats range (P < 0.0001). POF cases and controls had FSH concentrations of 133.7 versus 84.2 mIU/ml and 16.0 versus 6.2 mIU/ml for >30 repeats versus <30 repeats respectively. Inhibin B concentrations were not associated with CGG repeats. The results of this study indicate that FMR1 premutations are rare in sporadic cases of POF with no family history of fragile X syndrome. However, although in the normal polymorphic range, expansion of the CGG repeat tract to beyond 30 repeats was associated with serum FSH concentrations in both POF cases and controls.


Assuntos
Proteína do X Frágil da Deficiência Intelectual/genética , Insuficiência Ovariana Primária/genética , Adulto , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Índia , Reação em Cadeia da Polimerase , Polimorfismo Genético , Repetições de Trinucleotídeos
8.
Eur J Endocrinol ; 160(5): 855-62, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19211708

RESUMO

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a multigenic disorder, and insulin resistance is one of its hallmark features. Polymorphisms in exon 17 of insulin receptor (INSR) gene are reported to be associated with PCOS. We investigated this association in Indian women and its putative relationship with PCOS associated traits, which has not been explored so far. METHODS: In this case control study, the polymorphisms were investigated by direct sequencing in 180 women with PCOS and 144 age matched controls. Clinical, anthropometric, biochemical, and hormonal parameters were also estimated. RESULTS: The silent C/T polymorphism at His1058 in exon 17 of INSR was found to be present in our study population. The polymorphic genotype (CT+TT) was significantly associated with PCOS in lean women (chi(2)=8.493, df=1, P=0.004). It showed association with higher fasting insulin levels (P=0.02), homeostasis model assessment of insulin resistance (P=0.005), free androgen index (P=0.03), and lower quantitative insulin sensitivity check index (P=0.004) in lean PCOS women. No other novel or known polymorphism was identified in exon 17 in this cohort. CONCLUSIONS: The study shows significant association of C/T polymorphism at His1058 of INSR with PCOS in the lean rather than obese Indian women. Its association with indices of insulin resistance and hyperandrogenemia is also seen in the same group. The findings strengthen the concept that pathogenesis of PCOS is different in lean and obese women.


Assuntos
Antígenos CD/genética , Variação Genética/fisiologia , Hiperandrogenismo/genética , Resistência à Insulina/genética , Síndrome do Ovário Policístico/genética , Receptor de Insulina/genética , Magreza/genética , Adolescente , Adulto , Estudos de Casos e Controles , Análise Mutacional de DNA , Éxons/genética , Feminino , Humanos , Hiperandrogenismo/complicações , Hiperandrogenismo/metabolismo , Índia , Obesidade/complicações , Obesidade/genética , Obesidade/metabolismo , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/metabolismo , Magreza/complicações , Magreza/metabolismo , Adulto Jovem
9.
Fertil Steril ; 92(3): 1091-1103, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18793766

RESUMO

OBJECTIVE: To identify the proteins displaying differential expression in midsecretory phase endometrium as compared with proliferative phase endometrium. DESIGN: Prospective study with two groups of women in the midsecretory or proliferative phase. SETTING: Clinical research outpatient department. PATIENT(S): Healthy, regularly cycling women of proven fertility. INTERVENTION(S): Collection of endometrial biopsy samples. MAIN OUTCOME MEASURE(S): Image analysis software was used to compare two-dimensional protein maps of midsecretory phase endometrial tissues (MSE) with maps of proliferative phase endometrial tissues (PROE) and midsecretory phase uterine fluids (MSU). Matrix-assisted laser desorption/ionization time of flight in tandem (MALDI-TOF-TOF) analysis was carried out to identify eight proteins that were differentially expressed between the two phases and also to identify the spots that shared similar coordinates in the two-dimensional maps of MSE and MSU. RESULT(S): Densitometry analysis and subsequent MALDI-TOF-TOF analysis revealed up-regulation of calreticulin, the beta chain of fibrinogen, adenylate kinase isoenzyme 5, and transferrin in the PROE and of annexin V, alpha1-antitrypsin, creatine kinase, and peroxidoxin 6 in MSE compared with the other phase. Superimposition of the two-dimensional maps of MSE on those of MSU revealed the presence of heat-shock protein 27, transferrin, and alpha1-antitrypsin precursor in both endometrial tissues and uterine secretions. CONCLUSION(S): Differentially expressed proteins identified in the present study could be of relevance in endowing the endometrium with receptivity.


Assuntos
Endométrio/metabolismo , Fase Folicular/metabolismo , Perfilação da Expressão Gênica , Fase Luteal/metabolismo , Proteômica , Adenilato Quinase/metabolismo , Adulto , Anexina A5/metabolismo , Calreticulina/metabolismo , Creatina Quinase/metabolismo , Feminino , Fibrinogênio/metabolismo , Humanos , Estudos Prospectivos , Transferrina/metabolismo , alfa 1-Antitripsina/metabolismo
10.
Fertil Steril ; 92(2): 653-9, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18725155

RESUMO

OBJECTIVE: To analyze promoter regions of CYP11A1 and CYP17 for putative variations in a defined group of women with polycystic ovary syndrome (PCOS) and to study their association with androgen levels. DESIGN: Retrospective study. SETTING: A secondary referral center for infertility at National Institute for Research in Reproductive Health, Mumbai, India. PATIENT(S): One hundred women whose condition was diagnosed on the basis of the Rotterdam consensus were compared against 100 age-matched controls. INTERVENTION(S): A single sample of blood was collected after overnight fast on day 3 of the menstrual cycle. MAIN OUTCOME MEASURE(S): Plasma levels of T, androstenedione, 17alpha-hydroxyprogesterone, and DHEAS and nucleotide sequence of promoter regions of CYP11A1 and CYP17 genes. RESULT(S): Polymorphisms in promoter regions of the two key androgen-regulating genes, CYP11A1 and CYP17, were found to be significantly associated with T levels in the cohort of well-characterized PCOS cases as compared with controls. The significance was greater in the PCOS cases with both the polymorphisms. CONCLUSION(S): Our study carried out in a defined group of Indian women with PCOS suggests for the first time an individual, as well as combined, association of polymorphisms in CYP11A1 and CYP17 promoters with T levels.


Assuntos
Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Hidroxiesteroide Desidrogenases/genética , Hiperandrogenismo/epidemiologia , Hiperandrogenismo/genética , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/genética , Polimorfismo de Nucleotídeo Único/genética , Esteroide 17-alfa-Hidroxilase/genética , Comorbidade , Feminino , Predisposição Genética para Doença/genética , Humanos , Incidência , Índia/epidemiologia , Regiões Promotoras Genéticas/genética , Medição de Risco , Fatores de Risco , Adulto Jovem
11.
Reprod Biomed Online ; 17(2): 175-84, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18681990

RESUMO

Progesterone has been implicated in the process of spermatogenesis. This study aimed to investigate the association of progesterone receptor (PR) expression with spermatogenesis in the testis of infertile men. PR mRNA and protein were assessed by in-situ hybridization and immunohistochemistry in testicular biopsies obtained from 18 infertile men. The extent of spermatogenesis was assessed by Johnsen scoring. None of the patients included in the study had Yq microdeletions. PR expression was almost undetectable in all the testicular sections displaying Sertoli cell only (SCO) or arrest at spermatogonia. Weak cytoplasmic expression was observed in biopsies showing arrest at different stages of meiosis. In biopsies displaying spermatogenesis up to the round spermatid stages, PR expression was observed in both nucleus and cytoplasm of different cell types at intensity lower than that detected in normal biopsies. Normal PR expression was observed in biopsies demonstrating hypospermatogenesis. In biopsies showing mixed phenotypes, the tubules with SCO or spermatogonia arrest showed absence of PR expression; normal PR expression was observed in adjacent tubules showing complete spermatogenesis. Semi-quantitative assessment of PR expression and Johnsen scores in the testicular biopsies of infertile men demonstrating different phenotypes indicated a direct relationship between PR expression and extent of spermatogenesis.


Assuntos
Regulação para Baixo , Infertilidade Masculina/genética , Receptores de Progesterona/genética , Testículo/metabolismo , Adulto , Deleção Cromossômica , Cromossomos Humanos Y , Mutação em Linhagem Germinativa , Humanos , Infertilidade Masculina/metabolismo , Infertilidade Masculina/patologia , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores de Progesterona/metabolismo , Espermatogênese/genética , Testículo/patologia , Distribuição Tecidual
12.
J Clin Lab Anal ; 22(1): 29-38, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18200580

RESUMO

The genetic basis of infertility has received increasing recognition in recent years, particularly with the advent of assisted reproductive technology. It is now becoming obvious that genetic etiology for infertility is an important cause of disrupted spermatogenesis. Y-chromosome microdeletions and abnormal karyotype are the two major causes of altered spermatogenesis. To achieve biological fatherhood, intracytoplasmic sperm injection (ICSI) is performed in cases of severe infertility with or without genetic abnormalities. There is a concern that these genetic abnormalities can be transmitted to the male progeny, who may subsequently have a more severe phenotype of infertility. A total of 200 men were recruited for clinical examinations, spermiograms, hormonal profiles, and cytogenetic and Yq microdeletion profiles. Testicular biopsy was also performed whenever possible and histologically evaluated. Genetic abnormalities were seen in 7.1% of cases, of which 4.1% had chromosomal aberrations, namely Klinefelter's mosaic (47XXY) and Robertsonian translocation, and 3.0% had Yq microdeletions, which is very low as compared to other populations. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) were significantly increased in men with nonobstructive azoospermia (NOA) as compared to severe oligoasthenozoospermia (P<0.0001), whereas testosterone levels were significantly decreased in men with microdeletions as compared to men with no microdeletions (P<0.0083). Low levels of androgen in men with microdeletions indicate a need to follow-up for early andropause. Patients with microdeletions had more severe testicular histology as compared to subjects without deletions. Our studies showed a significant decrease (P<0.002) in the serum inhibin B values in men with NOA, whereas FSH was seen to be significantly higher as compared to men with severe oligoasthenozoospermia (SOAS), indicating that both the Sertoli cells as well the germ cells were significantly compromised in cases of NOA and partially affected in SOAS. Overall inhibin B in combination with serum FSH would thus be a better marker than serum FSH alone for impaired spermatogenesis. In view of the genetic and hormonal abnormalities in the group of infertile men with idiopathic severe oligozoospermia and NOA cases, who are potential candidates for ICSI, genetic testing for Y-chromosome microdeletions, karyotype, and biochemical parameters is advocated.


Assuntos
Infertilidade Masculina/patologia , Encaminhamento e Consulta , Adulto , Deleção Cromossômica , Cromossomos Humanos Y/genética , Loci Gênicos , Hormônios/sangue , Humanos , Índia , Masculino , Oligospermia/sangue , Oligospermia/patologia , Fenótipo , Reação em Cadeia da Polimerase , Proteínas de Plasma Seminal/genética , Sitios de Sequências Rotuladas , Testículo/patologia
13.
Reprod Biomed Online ; 15(5): 554-60, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18028747

RESUMO

Premature ovarian failure (POF) occurs in 1% of the general population and affects approximately 10% of non-ovulating women, resulting in infertility and sex steroid deficiency. The forkhead domain transcription factor (FOXL2) gene is one of the candidate genes associated with POF. This case-control study was designed for mutational analysis of the coding region of the FOXL2 gene in 80 cases of POF patients, 50 controls and 17 family members of 11 index cases using restriction fragment length polymorphism, single-stranded conformational polymorphism, heteroduplex analysis and direct DNA sequencing. A 738C-->T transition and a 773C-->G transversion were detected in two of the 80 patients and a family member of one index case, but in none of the 50 controls screened. No other alterations in the coding region of FOXL2 gene were detected. These data suggest that FOXL2 gene mutations are a rare occurrence in isolated POF cases and may not be involved in the pathogenesis of POF.


Assuntos
Fatores de Transcrição Forkhead/genética , Insuficiência Ovariana Primária/genética , Adulto , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Proteína Forkhead Box L2 , Análise Heteroduplex , Humanos , Índia , Mutação Puntual , Polimorfismo Conformacional de Fita Simples
14.
J Histochem Cytochem ; 55(12): 1181-90, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17652265

RESUMO

Serum anti-ovarian antibodies (AOAs) have been shown in autoimmune premature ovarian failure and in vitro fertilization-embryo transfer (IVF-ET) cases. The specificity of assays detecting these antibodies has been questioned. Researchers have used several techniques (e.g., ELISA and indirect immunofluorescence). Few have reported on the non-specificity and the type of molecular and cellular targets. We reported earlier on the presence of naturally occurring anti-albumin antibodies as the likely factor for non-specificity. Having developed a novel blocking recipe, we show substantial elimination of this non-specificity. With these standardized tests, we hereby report multiple targets at protein and histological levels. In our study group, 15 of 50 (30%) patients with premature ovarian failure and 13 of 50 (26%) IVF-ET patients showed the presence of AOAs. Western blotting showed a large number of patients making AOAs to a 90-kDa protein, followed by 97- and 120-kDa proteins. Histochemically, it was evident that the sera of these patients predominantly react with the oocyte; other somatic cellular targets are also involved. The specific non-invasive test developed by us was found to be useful because it could carry out a reliable diagnosis of an autoimmune etiology that would be very helpful to select patients in whom immune-modulating therapy could be recommended, which in turn may restore ovarian function and fertility.


Assuntos
Autoanticorpos/sangue , Infertilidade/imunologia , Ovário/imunologia , Insuficiência Ovariana Primária/imunologia , Adulto , Animais , Autoantígenos/sangue , Transferência Embrionária , Feminino , Fertilização in vitro , Humanos , Imunoensaio/métodos , Epitopos Imunodominantes/sangue , Imuno-Histoquímica , Infertilidade/terapia , Ratos , Ratos Sprague-Dawley , Sensibilidade e Especificidade
17.
Int J Fertil Womens Med ; 50(3): 140-3, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16279508

RESUMO

OBJECTIVE: Chlamydia trachomatis (CT) is implicated both in tubal infertility and in cervical dysplasia. Early detection of this infection is uncommon due to its asymptomatic nature and to lack of adequate health care facilities, leading to irreversible sequelae. This study evaluates the use of an introital specimen from women attending the Institute's infertility clinic to detect CT by polymerase chain reaction (PCR) and to correlate it with intraepithelial changes (IEC) of the cervix by Pap smears. METHODS: Introital and endocervical swab specimens were taken from 100 infertile women for PCR. An endocervical smear was taken for Pap staining. RESULTS: The CT infection rate was 34%. Sensitivity of introital and endocervical specimens for detection of CT was 82.4% and 85.3%, respectively (P > 0.05); both had 100% specificity. Sixty-seven percent of infected women were less than 30 years of age and only 15% of these reported discharge. Vaginitis/cervicitis was observed in 35% of the positive cases. IEC suggesting inflammation was seen in 74% of the infected women, as compared to 48% of subjects with normal cytology (p = 0.016). Being noninvasive, self collection of an introital specimen can be advocated in large-scale settings in our country for detection of CT in order to contain the infection and its complications.


Assuntos
Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis/isolamento & purificação , Teste de Papanicolaou , Pobreza , Esfregaço Vaginal/métodos , Adulto , Técnicas Bacteriológicas/estatística & dados numéricos , Infecções por Chlamydia/microbiologia , Feminino , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Incidência , Índia/epidemiologia , Infertilidade Feminina/prevenção & controle , Reação em Cadeia da Polimerase/métodos , Prevenção Primária/estatística & dados numéricos , Fatores de Risco , Serviços de Saúde Rural/estatística & dados numéricos , Saúde da Mulher
18.
Hum Reprod ; 20(11): 3039-46, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16024537

RESUMO

BACKGROUND: It is well established that endometrium undergoes extensive histological changes during implantation and subsequent stages of pregnancy in rodents as well as primates. Our previous investigation using a non-human primate model has demonstrated that morphological alterations are initiated even before the embryo invades the endometrium. The present study was undertaken to determine whether the embryo-induced morphological changes are accompanied by any alteration in the protein levels of the immunomodulatory cytokines and their regulators in the preimplantation stage endometrium. METHODS: The endometrial expression of immunosuppressive factors such as transforming growth factor beta2 (TGFbeta2), glycodelin (PP14), leukaemia inhibitory factor (LIF) and interleukin-6 (IL-6) were analysed on day 6 post-ovulation in pregnant and non-pregnant bonnet monkeys (Macaca radiata) using immunohistochemical methods. RESULTS: The endometrial expression of TGFbeta2, TGFbeta2 receptor, PP14 and IL-6 were significantly up-regulated (p < 0.05) in pregnant animals as compared to non-pregnant animals, whereas the expression of LIF and its receptor remained unaltered in pregnant animals. CONCLUSIONS: Expression levels of some immunomodulatory cytokines in endometrium are significantly increased even before the embryo invades the endometrium. The altered cytokine expression profile in endometrium probably contributes towards generating a conducive environment for the embryo survival, growth and development in the uterus.


Assuntos
Endométrio/metabolismo , Interleucina-6/biossíntese , Fator de Crescimento Transformador beta/biossíntese , Animais , Implantação do Embrião/fisiologia , Feminino , Glicoproteínas/biossíntese , Humanos , Fator Inibidor de Leucemia , Macaca radiata , Gravidez , Proteínas da Gravidez/biossíntese , Receptores de Fatores de Crescimento Transformadores beta/biossíntese
19.
J Reprod Immunol ; 66(1): 53-67, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15949562

RESUMO

Premature ovarian failure (POF) is a disorder of multicausal etiology leading to infertility in women. Development of ovarian auto-antibodies is a causative factor in most POF cases, but no consensus on the ovarian antigenic determinants has been reached till date. In the present study, sera from 15 POF cases, seven normally cycling women and eight menopausal women were studied by immunohistochemistry (IHC) for the presence of anti-ovarian antibodies. 10 of the 15 POF sera (66.6%) presented with anti-ovarian antibodies (Ao). Of these, two demonstrated antibodies to the zona pellucida (ZP) as well as strong immunoreactivity to granulosa cells (Azg), while the remaining eight exhibited anti-ZP antibodies with negligible staining in granulosa cells (Az). The antibodies showed cross-reactivity with ZP from various species such as human, sheep, marmoset, pig and mouse. Among various murine tissues, the antibodies cross-reacted only with thyroid and not with uterus, spleen, kidney, liver, adrenal, pancreas and pituitary. Five of the eight Az individuals presented with significant titres of anti-thyroid antibodies (Azt). In the control group, one menopausal control presented with reactivity to both ZP and GC, the autoimmunity possibly being a consequence of surgical trauma; while one normally cycling woman tested positive for anti-thyroid antibodies. The IHC results were confirmed by ELISA using heat-solubilized isolated ZP (SIZP) as the antigen. Out of seven Ao samples assessed by ELISA, five reacted with SIZP. Preincubation of these five samples with varying concentrations of SIZP demonstrated a dose-dependent decrease in reactivity in ELISA and abolished staining in IHC, confirming the specificity of auto-antibodies to ZP in the POF group. Our results thus suggest that ZP is an important ovarian antigen in autoimmune POF.


Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Insuficiência Ovariana Primária/imunologia , Zona Pelúcida/imunologia , Adulto , Animais , Callithrix , Reações Cruzadas/imunologia , Feminino , Humanos , Camundongos , Ovário/imunologia , Ovinos , Suínos , Glândula Tireoide/imunologia
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