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1.
Anal Methods ; 16(29): 5060-5068, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38989641

ABSTRACT

In recent years, the incidence of infertility has increased year by year. Assisted reproductive technology (ART) is one of the effective strategies to treat infertility. In the process of ART, commonly used methods for sperm separation have shortcomings and there is still room for improvement. In this study, a functional sperm selection strategy was established based on hyaluronic acid (HA) modified magnetic microbeads (MBs) and a supporting two-dimensional electromagnetic manipulation device system. Due to the modification of HA on the surface of MBs, the HA-MBs have the ability to target and bind to specific receptors on the sperm membrane to form a sperm-MB complex. A disulfide linker was introduced to connect HA and MBs. After modifying HA and connecting it with the disulfide linker, the sperm of sperm-MBs can be released under the combined effect of hyaluronidase and reduced GSH with the disulfide bond broken and HA degraded. A two-dimensional electromagnetic manipulation system was introduced to generate a magnetic field and control the directional movement of the sperm-MB complex under the guidance of an inverted microscope. The free MBs can also be removed after the sperm is released. Furthermore, the mouse sperm selected through this strategy can achieve normal insemination via ICSI and the obtained blastocysts have normal morphology and developmental milestones. This strategy has potential to be developed into an automated screening solution for the screening of functional sperm for assisted reproductive technology.


Subject(s)
Hyaluronic Acid , Microspheres , Spermatozoa , Hyaluronic Acid/chemistry , Male , Animals , Mice , Cell Separation/methods , Sperm Injections, Intracytoplasmic/methods , Female
2.
Comput Intell Neurosci ; 2022: 6530884, 2022.
Article in English | MEDLINE | ID: mdl-36199963

ABSTRACT

Objective: This investigation was to test the potential role of m6A-related long non-coding RNAs (lncRNAs) and immune infiltration as crucial factors in the diagnosis and treatment of uterine corpus endometrial cancer (UCEC). Method: The UCEC RNA-seq data were downloaded in the Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov/). There were 587 samples totally, containing 543 UCEC cases and 35 healthy cases. The clinical information of UCEC cases included survival time, survival status, gender, age, stage, and TMN stage. Twenty-three m6A-related genes were found in published journals. The RNA-seq documents of UCEC were downloaded in the Cancer Genome Atlas (TCGA). The hub gene data of UCEC were downloaded from GEPIA2 database. The different packages of R language were applied to calculate and analyze in this research. Results: Among 587 cases in our study, we discovered 3039 lncRNAs in the TCGA-UCEC database. After the differential analysis, 23 m6A-associated genetics were screened and twenty-one m6A-associated differential genetics were found. In the end, we obtained 20 m6A-related lncRNAs. LNCTAM34A was considered as a predictive gene through univariate and multivariate Cox regression analysis. In addition to the above, patients with high LNCTAM34A expression had better outcomes than those with low LNCTAM34A expression. The high-risk cohort had greater scores of activated dendritic cells (aDCs), B cells, and T cell regulatory (Tregs) than low-risk cohort; in the meanwhile, high-risk cohort had lower scores of DCs and iDCs. Then, the high-risk cohort displayed greater scores in the immune functions of MHC class I, para-inflammation, and type I IFN response than those of low-risk cohort. Among 27 immune-inducible genes, the level of CD244, KIR3DLI, NRP1, PDCD1LG2, and TNFRSF8 was reduced in UCEC samples and the level of CD27, CD28, CD70, CD80, CD86, HAVCR2, ICOS, IDO1, LAIR1, PDCD1, TIGIT, TNFRSF18, -25, -9, -14, and VTCN1 was increased in UCEC samples. Conclusion: The key role of M6A-related lncRNAs in immune microenvironment in high-risk patients of UCEC. The patients with strong expression of LNCTAM34A have a good prognosis, and LNCTAM34A can be used as a prognostic gene for UCEC. m6A-related lncRNAs can be used as a potential treatment for UCEC. Our observations can be used as a hypothetical basis for future in vitro and animal experiments.


Subject(s)
Endometrial Neoplasms , RNA, Long Noncoding , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , CD28 Antigens/genetics , CD28 Antigens/metabolism , Endometrial Neoplasms/genetics , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Female , Gene Expression Regulation, Neoplastic , Genes, Neoplasm , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Tumor Microenvironment
4.
Mol Cell Endocrinol ; 490: 15-20, 2019 06 15.
Article in English | MEDLINE | ID: mdl-30922932

ABSTRACT

The steroidogenic acute regulatory protein (STAR) governs the rate-limiting step in steroidogenesis, and its expression varies depending on the needs of the specific tissue. It is well known that tight control of steroid production is essential for multiple processes involved in reproduction. We recently showed that Star is regulated at the posttranscriptional level in vitro by H19 and let-7. Here we demonstrate that this novel regulatory mechanism is functional in vivo, regulated by cAMP, and that loss of H19 not only disrupts ovarian STAR but also results in altered progesterone production in an H19KO mouse model. This work further strengthens the possibility that noncoding-RNA-mediated regulation of STAR may play an important role in the regulation of steroid hormone production, and contributes further to our understanding of the many ways in which this important gene is regulated.


Subject(s)
Ovary/metabolism , Phosphoproteins/metabolism , Progesterone/biosynthesis , RNA, Long Noncoding/metabolism , Animals , Cell Line, Tumor , Cyclic AMP/biosynthesis , Female , Humans , Mice, Inbred C57BL , RNA, Long Noncoding/genetics
5.
Biol Reprod ; 100(1): 101-111, 2019 01 01.
Article in English | MEDLINE | ID: mdl-30137224

ABSTRACT

In reproductive age women, the pool of primordial follicles is continuously depleted through the process of cyclic recruitment. Anti-Mullerian hormone (AMH) both inhibits the initial recruitment of primordial follicles into the growing pool and modulates the sensitivity of growing follicles to follicle stimulating hormone. Thus, AMH may be an important modulator of female infertility and ovarian reserve; however, the mechanisms regulating AMH remain unclear.To evaluate AMH levels in the absence of H19 lncRNA, H19 knockout (H19KO) mice were evaluated for analysis of ovarian AMH gene expression, protein production, and reproductive function, including assessment of follicle numbers and litter size analysis. To further investigate regulation of AMH by the H19/let-7 axis, let-7 binding sites on AMH were predicted, and in vitro studies of the effect of H19 knockdown/overexpression with let-7 rescue were performed. Lastly, response to superovulation was assessed via oocyte counts and estradiol measurements.The H19KO mouse demonstrates subfertility and accelerated follicular recruitment with increased spontaneous development of secondary, preantral, and antral follicles. Ovaries of H19KO mice have decreased AMH mRNA and protein, and AMH mRNA has a functional let-7 binding site, suggesting a plausible ncRNA-mediated mechanism for AMH regulation by H19/let-7. Lastly, in the absence of H19, superovulation results in higher estradiol and more oocytes, suggesting that H19 functions to limit the number of follicles that mature, produce estradiol, and ovulate. Thus, AMH's inhibitory actions are regulated at least in part by H19, likely via let-7, marking this ncRNA pair as important regulators of the establishment and maintenance of the follicular pool.


Subject(s)
Anti-Mullerian Hormone/genetics , Anti-Mullerian Hormone/metabolism , MicroRNAs/physiology , RNA, Long Noncoding/physiology , Animals , Cells, Cultured , Female , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , MicroRNAs/genetics , RNA Interference , RNA, Long Noncoding/genetics , Signal Transduction/genetics
6.
Reprod Biomed Online ; 35(5): 609-615, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28887105

ABSTRACT

The aim of this study was to investigate whether polymorphism and expression of CYP17, CYP1A1, COMT and SULT1A1 affected the risk of idiopathic primary ovarian insufficiency (POI) in Chinese women. DNA sequencing and real-time PCR were used to detect these genes in 132 cases of idiopathic POI and 132 normal women. A significant increase in the C allele of CYP17 (rs743572) polymorphism was observed in women with POI compared with controls (PFDR = 0.046). A significant decrease was observed in the C allele of CYP1A1 (rs4646903) in women with POI compared with controls (PFDR = 0.004). The A allele of COMT (rs4680) polymorphism was more frequent in women with POI compared with controls (PFDR = 0.029). The genotypic frequency of SULT1A1 (rs9282861) was not significantly different between the two groups. For the relative expression of CYP17 and COMT were statistically significant (both PFDR = 0.066), with false discovery rate controlled at 0.1. No significant difference was observed in the RNA levels of CYP1A1 and SULT1A1 between the two groups. The frequency of expression of the CYP17 T/C variant tended to be higher and the A allele of COMT polymorphism together with down-regulation of its mRNA expression may be more frequent in Chinese women with idiopathic POI.


Subject(s)
Arylsulfotransferase/genetics , Catechol O-Methyltransferase/genetics , Cytochrome P-450 CYP1A1/genetics , Estrogens/metabolism , Gene Expression , Polymorphism, Single Nucleotide , Primary Ovarian Insufficiency/genetics , Steroid 17-alpha-Hydroxylase/genetics , Adult , Case-Control Studies , China , Female , Genotype , Humans
7.
J Med Syst ; 41(8): 131, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28748429

ABSTRACT

In China, day surgery has been promoted because its operation time and post-operative hospital stay are shorter than those of elective surgery. Day surgery can speed up the turnover of beds and operation rooms. Usually, the conditions of elective surgery patients are more complicated than those of day surgery patients. The development of the discipline, which means that the hospital has improved the skills of the doctors and the ability of doctors to cope with serious diseases and has increased the overall medical level of the hospital, requires surgeons to operate in some complicated elective surgeries. In the case of operating rooms and beds in short supply, there is a trade-off between the promotion of day surgery and the development of the discipline. Day surgery is relatively uncomplicated, but it requires more highly qualified surgeons. However, the development of the discipline requires surgeons to take on some complicated elective surgeris. Moreover, according to the notion of grading treatment, class-A tertiary hospitals are more suitable for patients with relatively complicated and serious conditions. In the emerging context of day surgery, highly qualified surgeons need to perform both day surgeries and elective surgeries. This paper studied how to control the admission of surgery patients. We take into account both day surgery promotion and discipline development in decision-making. A dynamic programming model was built for admission control, and a γ-adjust-threshold heuristic policy was proposed. We then compared the heuristic policy to three other policies through simulation. The results show that our heuristic policy outperforms the hospital's target policy.


Subject(s)
Hospitalization , China , Elective Surgical Procedures , Humans , Operating Rooms
8.
Zhonghua Fu Chan Ke Za Zhi ; 50(2): 116-9, 2015 Feb.
Article in Chinese | MEDLINE | ID: mdl-25877608

ABSTRACT

OBJECTIVE: To assess the influence of length of the alanine tract of forkhead box E1 (FOXE1) gene on genetic susceptibility to idiopathic premature ovarian failure (POF). METHODS: Totally 110 patients with idiopathic POF were recruited between February 2009 and December 2012 at the Affiliated Shenzhen City Maternity and Child Healthcare Hospital of Southern Medical University. Controls (n = 110) were individuals with normal menstrual cycles, normal FSH concentrations. The polyalanine tract and flanking sequence of FOXE1 were screened using the multiplex ligation-dependent probe amplification (MLPA) technique and direct sequence technique. RESULTS: The most frequent of FOXE1 polyalanine stretch length was 14 residues in both groups. The length of FOXE1 polyalanine reported in this study varied from 12 to 16 alanines, and three variants of FOXE1-polyalanine length, containing 12, 14, or 16 alanine residues, and 5 different genotypes were identified. The most common genotypes were 14/14 homozygote, occurring with the frequency of 81.8% (90/110) in the POF group, while 96.4% (106/110) in control subjects, respectively. The incidence of 14/14 genotypes of FOXE1-polyalanine was significantly lower in patients with POF (χ² = 119.730, P = 0.001) in comparison to the controls. There were significantly higher frequencies of the 16/16 genotypes in cases with POF [10.0% (11/110) versus 0; χ² = 3.403, P = 0.001], as compared with the controls. The FOXE1 14 alanine allele was significantly less common in the POF patient group than the controls [84.5% (186/220) versus 98.2% (216/220); χ² = 25.923, P = 0.001]. The FOXE1 16 alanine allele was significantly more common in the POF patient group than the controls [12.7% (28/220) versus 1.8% (4/220); χ² = 19.412, P = 0.001]. CONCLUSIONS: The polymorphism of the polyalanine tract of FOXE1 gene have a certain relevance for the genetic aetiology of idiopathic POF.


Subject(s)
Forkhead Transcription Factors/genetics , Peptides/metabolism , Polymorphism, Genetic , Primary Ovarian Insufficiency/genetics , Alleles , Case-Control Studies , Female , Genetic Predisposition to Disease , Genotype , Humans , Multiplex Polymerase Chain Reaction
9.
Reprod Biomed Online ; 29(3): 311-8, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24912417

ABSTRACT

The aim of this study was to investigate the role of the anti-Müllerian hormone (AMH) signalling pathway in the pathophysiology of idiopathic primary ovarian insufficiency (POI) and age at natural menopause (ANM) using a genetic approach. DNA sequencing was used to detect the genotype distribution and allele frequency of the genes AMH and AMH receptor II (AMHR2) in 120 cases of idiopathic POI and 120 normal-ANM women. Fourteen sequence variants of AMHR2, including 10 novel variants, were identified. Two novel exonic missense variants were p.I209N and p.L354F. The missense variant p.I209N, which is conserved in different species, was predicted to have functional and structural impacts on the AMHR2 protein. The clinical significance of one additional variant (p.L354F) remains arguable pending functional studies. The genotype frequencies of AMH and AMHR2 were similar in distribution for POI patients and normal-ANM women. These findings suggest that POI patients and normal-ANM women in China share AMH and AMHR2 genetic variants. The AMH signalling pathway associated with ANM also may contribute to POI.


Subject(s)
Anti-Mullerian Hormone/genetics , Menopause/genetics , Primary Ovarian Insufficiency/genetics , Receptors, Peptide/genetics , Receptors, Transforming Growth Factor beta/genetics , Adult , Asian People , China , Exons , Female , Gene Frequency , Genetic Variation , Genotype , Humans , Middle Aged
10.
Zhonghua Fu Chan Ke Za Zhi ; 48(6): 432-6, 2013 Jun.
Article in Chinese | MEDLINE | ID: mdl-24103122

ABSTRACT

OBJECTIVE: To evaluate clinical value of denaturing high performance liquid chromatography (DHPLC) used in detecting transforming growth factor beta receptor 3 (TGFBR-3) exons 11 and 12 polymorphism in women with idiopathic premature ovarian failure (POF). METHODS: From Feb. 2009 to Dec. 2011, 110 patients with idiopathic POF undergoing treatment at Shenzhen Maternal & Child Health Institute affiliated to Southern Medical University were enrolled as POF group in this study. In the mean time, 110 women under 40 years old with normal hormonal level and menstrual cycles as control group. The exons 11 and 12 of TGFBR-3 gene polymorphism were screened by using DHPLC, and results of DNA sequencing was as golden standard. Some related indexes were calculated, such as sensitivity, specificity, false negative value, false positive value, Youden index, positive predictive value, and negative predictive value. At the same time, 20% of the tested specimens were chosen randomly and detected by DHPLC again. The value of Kappa index were calculated by comparing the results between the first and second DHPLC analysis. RESULTS: The exon 11 of TGFBR-3 were not identified gene polymorphism and two nucleotide polymorphisms were identified in exon 12. For 2022 T/C polymorphism, the frequencies of CC with 0.9% (1/110), TC with 22.7% (25/110), TT with 76.4% (84/110), C with 12.3% (27/220) and T with 87.7% (193/220) in POF group were significantly different from CC with 0, TC with 9.1% (10/110) and TT with 90.9% (100/110), C with 4.5% (10/220) and T with 95.5% (210/220) in control group (all P<0.05). Allelic and genotypic frequencies of 2161-75 C/T were not differed significantly between the two groups (all P>0.05). As DNA sequencing as golden standard, DHPLC showed that the sensitivity was 100%, specificity was 97.9%, Youden index was 97.9%, positive predictive value was 96.3%, negative predictive value was 100%, and Kappa index was 0.888 (P<0.05). CONCLUSION: DHPLC analysis is higher validity, reliability and practicability method in detecting TGFBR-3 polymorphism in idiopathic premature ovarian failure.


Subject(s)
Polymorphism, Single Nucleotide , Primary Ovarian Insufficiency/genetics , Proteoglycans/genetics , Receptors, Transforming Growth Factor beta/genetics , Adult , Asian People/genetics , Case-Control Studies , Chromatography, High Pressure Liquid , Exons/genetics , Female , Gene Frequency , Genetic Association Studies , Genotype , Humans , Polymerase Chain Reaction , Sensitivity and Specificity , Sequence Analysis, DNA
11.
Am J Obstet Gynecol ; 207(6): 511.e1-7, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23099193

ABSTRACT

OBJECTIVE: The purpose of this study was to assess the receptivity of the homogeneous endometrium in the late follicular phase in infertile women with natural cycles. STUDY DESIGN: Twenty-eight infertile women with ultrasonographically homogeneous (group 1) or trilaminar (group 2) endometria in the late follicular phase underwent endometrial biopsies. Some molecular markers and development of pinopodes were evaluated. RESULTS: In the late follicular phase, the mean level of vascular endothelial growth factor was significantly lower in group 1 than in group 2 (0.96 ± 0.37 marks vs 1.39 ± 0.46 marks; P = .010). In the mid luteal phase, a decreased leukemia inhibitory factor and integrin alpha v beta 3 levels were found in group 1 (1.58 ± 0.99 marks vs 2.59 ± 0.61 marks; 1.85 ± 0.72 marks vs 2.60 ± 0.73 marks; 1.92 ± 0.91 marks vs 2.83 ± 0.57 marks; P = .003; P = .011; P = .004). The rate of fully developed pinopodes in the mid luteal phase was significantly decreased in group 1 (P = .018). CONCLUSION: An ultrasonographically homogeneous endometrium in the late follicular phase was associated with poor receptivity in infertile women with natural cycles.


Subject(s)
Endometrium/diagnostic imaging , Follicular Phase , Infertility, Female/blood , Leukemia Inhibitory Factor/blood , Luteal Phase , Vascular Endothelial Growth Factor A/metabolism , Adult , Biopsy , Endometrium/physiopathology , Female , Gene Expression , Humans , Immunohistochemistry , Leukemia Inhibitory Factor/genetics , Microscopy, Electron, Scanning , Ultrasonography , Vascular Endothelial Growth Factor A/genetics
12.
Hum Reprod ; 27(7): 2201-7, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22513983

ABSTRACT

BACKGROUND: This retrospective cohort study was to determine the frequency and types of chromosomal abnormalities in Han Chinese women with well-documented premature ovarian failure (POF). METHODS: Karyotype analysis and correlation to phenotypes were performed on 531 Chinese patients with proven POF (FSH > 40 mIU/ml) attending four reproductive centers in China. G-banded metaphase chromosomes were prepared and analyzed, with mosaicism excluded by counting up to 100 cells from lymphocytes. RESULTS: Chromosomal abnormalities were present in 64 of 531 (12.1%) POF cases, of which 32 were X-structural aberrations (7 mosaic): 15 del(Xq), 2 del(Xp), 11 isochromosomes [6 i(Xp); 5 i(Xq)], 1 ring chromosome (mosaic), 1 inversion (mosaic), 1 isodicentric chromosome and 1 complex arrangement. Nine non-mosaic X-autosome translocations were detected, all but 1 involving Xq. Aneuploidy without a structurally abnormal X was found in 19 cases: 7 non-mosaic 45,X, 9 45,X mosaicisms and 3 47,XXX (1 mosaic with 46,XX line). Karyotypic abnormalities were more frequent in patients with primary amenorrhea (15/70, 21.4%) than those with secondary amenorrhea (49/461, 10.6%; P = 0.01). 45,X and 45,X/46,XX mosaicism were the complements most frequently associated with primary amenorrhea (46.7%). Two of the three cases with 46,XY or 45,X/46,XY karyotype presented with 'secondary amenorrhea'. One balanced autosomal Robertsonian translocation was also detected. CONCLUSIONS: The overall prevalence of chromosomal abnormalities was 12.1% in this first large scale report of chromosomal aberrations in Chinese women with POF. In one of the largest samples of women with POF reported from any population, the prevalence of X-structural abnormalities, X-autosome translocations and X aneuploidy confirms the essential role X chromosomal abnormalities play in POF.


Subject(s)
Cytogenetic Analysis/methods , Primary Ovarian Insufficiency/ethnology , Primary Ovarian Insufficiency/genetics , Adult , China , Chromosome Aberrations , Chromosome Banding , Chromosomes, Human, X/genetics , Cohort Studies , Female , Follicle Stimulating Hormone/blood , Humans , Karyotyping , Lymphocytes/cytology , Metaphase , Phenotype , Prevalence , Retrospective Studies
13.
Eur J Obstet Gynecol Reprod Biol ; 162(1): 50-4, 2012 May.
Article in English | MEDLINE | ID: mdl-22397748

ABSTRACT

OBJECTIVE: To assess the effectiveness of repeated transvaginal ultrasound-guided ovarian interstitial laser treatment in the management of anovulatory patients with polycystic ovary syndrome (PCOS). STUDY DESIGN: A retrospective study was performed in our department on 27 anovulatory PCOS women who failed to respond to the first ultrasound-guided transvaginal ovarian interstitial laser treatment. Each woman received a repeat procedure and postoperative rates of ovulation and pregnancy were monitored. RESULTS: Of 27 patients, 18 (66.67%) ovulated spontaneously following the repeated ultrasound-guided transvaginal ovarian interstitial laser treatment Ten women became pregnant within six postoperative months and a cumulative pregnancy rate of 37.04% was achieved. There were no significant operative complications. CONCLUSION: Repeated ultrasound-guided transvaginal ovarian interstitial laser treatment is an effective and safe management in anovulatory PCOS patients who fail to respond or have a transient response to the first transvaginal ovarian interstitial laser treatment.


Subject(s)
Anovulation/surgery , Infertility, Female/surgery , Laser Coagulation/methods , Polycystic Ovary Syndrome/surgery , Adult , Anovulation/diagnostic imaging , Anovulation/etiology , Female , Humans , Infertility, Female/diagnostic imaging , Infertility, Female/etiology , Ovary/surgery , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/diagnostic imaging , Pregnancy , Retrospective Studies , Treatment Outcome , Ultrasonography
14.
Gynecol Endocrinol ; 28(1): 63-7, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21756058

ABSTRACT

This study screened the TGFBR3 mutations in Chinese patients with idiopathic premature ovarian failure (POF) to gain a better understanding the genetic aetiology of POF. One hundred twelve Chinese patients with idiopathic POF and 110 women from normal controls were examined. The coding region and respective flanking intronic regions of the TGFBR3 gene were amplified by the PCR, and the DNA fragments were directly sequenced. Twenty-eight sequence variants, including 12 novel variants, were identified. These novel variants included three missense mutations, two synonymous mutations, and seven mutations in the intronic region. Three novel exonic missense variants were p.E458G, p.P824L, and p.I836V. The c.566-216G>A, c.566-71C>T, c.2022T>C, c.2502A>G, and c.2568G>A variants represented significantly different genotype distribution between POF cases and the controls. The binary logistic regression analysis of c.566-216G>A, c.566-71C>T, and c.2502A>G variants were significantly associated with the POF patients and the ATTAG haplotype was most significantly over-represented as compared with controls (P = 0.00121). The ATTGG and GCTGG haplotypes were significantly higher in controls than in patients (P = 0.00113 and 0.00055, respectively). Other less frequent haplotypes, such as GCCGA, was only present in the patients (P = 0.00066). GTTGG was only present in the controls (P = 0.00001). Significant diversity of genotype distribution and haplotype analysis suggested that TGFBR3 mutations may be responsible for the genetic aetiology of idiopathic POF in Chinese patients.


Subject(s)
Asian People/genetics , Haplotypes , Primary Ovarian Insufficiency/genetics , Proteoglycans/genetics , Receptors, Transforming Growth Factor beta/genetics , Adult , Case-Control Studies , DNA Mutational Analysis , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Models, Biological , Mutation, Missense , Polymorphism, Single Nucleotide , Primary Ovarian Insufficiency/epidemiology , Primary Ovarian Insufficiency/ethnology
15.
Hum Mol Genet ; 21(2): 430-6, 2012 Jan 15.
Article in English | MEDLINE | ID: mdl-21989058

ABSTRACT

Premature ovarian failure (POF) is a complex heritable disorder known to be caused by chromosomal abnormalities and to date a limited number of known mutations, often autosomal. We sought to identify additional genetic loci associated with POF by performing the first large-scale genome-wide association study (GWAS). GWAS, using Affymetrix SNP 6.0 chip, was conducted in an initial discovery set of 391 well-documented (follicle-stimulating hormone >40 IU/ml) Chinese Han POF patients, compared with 895 unrelated Chinese female controls. A replication study on the most significant loci was then performed in an independent set of 400 cases and 800 controls. Suggestive significant associations were observed at 8q22.3. Replication of eight single-nucleotide polymorphisms (SNPs) (rs10464815, rs10808365, rs3847152, rs3847153, rs3847154, rs3843552, rs10955242, rs3843555) (P ≤ 3.86 × 10(-6)) was confirmed in verification sets. No specific candidate gene was found in the immediate region of 8q22.3. This GWAS, involving by far the largest sample of POF cases accumulated to date, revealed heretofore unrecognized association between POF and a novel genetic locus or region of unknown nature on 8q22.3. We speculate existence of a long-distance regulatory region that has relevance to the control of ovarian differentiation or oogenesis. Given failure to find association with any of the other autosomal regions known to harbor genes causing ovarian failure, our findings also underscore the likelihood of considerable genetic and etiologic heterogeneity in POF and the need for additional approaches like whole-genome sequencing.


Subject(s)
Chromosomes, Human, Pair 8 , Ethnicity/genetics , Primary Ovarian Insufficiency/genetics , Case-Control Studies , China , Female , Humans , Polymorphism, Single Nucleotide
16.
Reprod Biol Endocrinol ; 9: 158, 2011 Dec 16.
Article in English | MEDLINE | ID: mdl-22177572

ABSTRACT

BACKGROUND: FOXE1 is one of the candidate genes for genetic predisposition to premature ovarian failure (POF) and it contains an alanine tract. Our purpose is to assess the influence of length of the alanine tract of FOXE1 on genetic susceptibility to POF. METHODS: The group studied consisted of 110 Chinese patients with idiopathic POF and 110 women from normal controls. The polyalanine tract and flanking sequence of FOXE1 was screened using the Multiple Ligation-dependent Probe Amplification (MLPA) technique and directly sequenced. RESULTS: Three variants of FOXE1-polyalanine length, containing 12, 14, or 16 alanine residues, and 5 different genotypes were identified. There were significantly lower frequencies of the 14/14 genotypes in cases with POF (X2 = 119.73, P = 0.001), as compared with the controls. The incidence of 16/16 genotypes of FOXE1-polyalanine was significantly higher in patients with POF (X2 = 3.403, P = 0.001) in comparison to the controls. The FOXE1 14 alanine allele was significantly less common in the POF patient group (186/220) than the controls (216/220) (X2 = 25.923, P = 0.0001). The FOXE1 16 alanine allele was significantly more common in the POF patient group (28/220) than the controls (4/220) (X2 = 19.412, P = 0.0001). CONCLUSION: This finding provides evidence that polyalanine repeat expansions in FOXE1 may be responsible for the genetic aetiology of POF in Chinese women.


Subject(s)
Forkhead Transcription Factors/genetics , Primary Ovarian Insufficiency/genetics , Adolescent , Adult , DNA Repeat Expansion , Female , Forkhead Transcription Factors/chemistry , Genetic Testing/methods , Genotype , Humans , Peptides/chemistry
17.
Reprod Biomed Online ; 23(6): 697-703, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22036907

ABSTRACT

The aim of this study was to assess the association between human transforming growth factor ß receptor, type III (TGFBR3) and idiopathic premature ovarian failure (POF) in a Chinese population. A total of 112 Chinese women with idiopathic POF and 110 normal controls were examined. DNA samples prepared from blood leukocytes were used as templates for polymerase-chain reaction amplification of DNA fragments from TGFBR3. The gene fragments were sequenced. Web-based programs, including PolyPhen, Sorting Intolerant from Tolerant (SIFT), Prediction of Pathological Mutations (PMUT), ScanProsite and ClustalW2, were used to predict the potential functional and structural impacts of the missense variants of TGFBR3. A total of 11 novel variants were identified. Among them, six were found only in the POF patients. Two missense variants, p.E459G and p.P825L, which are conserved in primates, were predicted to have functional and structural impacts on the TGFBR3 protein. The other four variants (c.381+12A>C, c.2431-7A>G, p.S172S and p.C220C) were considered benign. However, further functional studies are necessary to confirm these findings.


Subject(s)
Mutation, Missense , Primary Ovarian Insufficiency/genetics , Proteoglycans/genetics , Receptors, Transforming Growth Factor beta/genetics , China , DNA Mutational Analysis , Female , Humans , Sequence Analysis, Protein
18.
Nan Fang Yi Ke Da Xue Xue Bao ; 31(5): 886-9, 2011 May.
Article in Chinese | MEDLINE | ID: mdl-21602150

ABSTRACT

OBJECTIVE: To summarize the clinical features of idiopathic premature ovarian failure (POF) and explore the early diagnosis and intervention. METHODS: A retrospective study was conducted in 39 women with idiopathic POF treated between February, 2009 and January, 2010. The clinical data of the patients including the menstrual feature, POF incidence, vaginal ultrasound and pregnancy outcomes were investigated. RESULTS: One patient had primary amenorrhea and 38 had secondary amenorrhea with an average duration of amenorrhea of 5.82 years. Abrupt cessation occurred after 1-2 menstruations following the menarche in 2 cases (5.1%) and without identifiable preceding signs in 9 cases (23%). The mean uterine and ovarian volume was significantly smaller in POF group than in the control group. Antral follicle count (AFC) was also significantly lower in POF group. Vaginal ultrasound detected at least one ovary in 89.7% and follicular activity in 79.5% of the POF patients. Evidence of ovulation was found in 12 patients, and spontaneous pregnancy occurred in 2 patients with a pregnancy rate of 5.1%. CONCLUSION: Patients with menstrual disturbance, polymenorrhea and oligomenorrhea are at risk of developing POF, in which case regular detection of the mean uterine volume, ovarian volume and AFC by vaginal ultrasound may help in early POF detection. Close monitoring can be necessary in the course of hormone replacement therapy, and timely intervention with assisted reproductive techniques may increase the chance of pregnancy.


Subject(s)
Primary Ovarian Insufficiency/diagnosis , Adult , Female , Humans , Pregnancy , Retrospective Studies , Risk Factors , Young Adult
19.
Zhonghua Fu Chan Ke Za Zhi ; 39(10): 687-9, 2004 Oct.
Article in Chinese | MEDLINE | ID: mdl-16144567

ABSTRACT

OBJECTIVE: To discuss the clinical feature, diagnosis and treatment options of adolescent endometriosis. METHODS: The records of adolescent patients with endometriosis (11-20 years old) who were admitted to First, Second and Third Affiliated Hospital of Zhongshan University and Guangdong Provincial People's Hospital between 1990 and 2003 were retrospectively reviewed. RESULTS: Forty-three patients were diagnosed as endometriosis either by laparotomy or laparoscopy. The chief symptoms leading to the diagnosis were palpable pelvic mass (18/43), dysmenorrhea (15/43), chronic pelvic mass (10/43) and acute pelvic pain (4/43). The majority of patients (53%) presented with the revised AFS-r classification stage III, 8 cases (19%) presented with stage I, 3 cases (7%) with stage II and 9 cases (21%) with stage IV. Nine cases (21%) had complicated genital tract abnormalities. Conservative operations, including salpingo-oophorectomy ins cases, ovarian cystectomy in 31 cases and laparoscopic vaporization in 8 cases, were performed. Surgeries were followed by hormonal suppression using oral contraceptives in a continuous or cyclic manner. CONCLUSIONS: Adolescent endometriosis may occur around 4.6 years after menarche. The chief symptoms are palpable pelvic mass and dysmenorrhea. The treatment of endometriosis in adolescence does not differ principally from that in adult women. In the treatment of endometriosis and for the prevention of recurrence, it is recommended to give 3-6 months of oral contraceptives.


Subject(s)
Endometriosis/diagnosis , Endometriosis/therapy , Adolescent , Adult , Endometriosis/epidemiology , Female , Humans , Male
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