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Yongyong Shi,
Han Zhao,
Yuhua Shi,
Yunxia Cao,
Dongzi Yang,
Zhiqiang Li,
Bo Zhang,
Xiaoyan Liang,
Tao Li,
Jianhua Chen, [......],
Dongni Zhao,
Chun-e Ren,
Xiuqing Li,
Wei Zhang,
Yiwen Zhang,
Jiangtao Zhang,
Di Wu,
Changming Zhang,
Lin He,
Zi-Jiang Chen
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ABSTRACT: Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10(-8): 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS.
Nature Genetics 08/2012; 44(9):1020-5. · 35.53 Impact Factor
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ABSTRACT: To find the association between recurrent spontaneous abortion (RSA)/early embryo growth arrest and Y chromosome polymorphism.
Peripheral blood samples of the male patients of big Y chromosome, small Y chromosome and other male patients whose partners suffered from unexplained RSA/early embryo growth arrest were collected. PCR and real-time fluorescent quantitative PCR were used to test the deletion and the copy number variation of DYZ1 region in Y chromosome of the patients. A total of 79 big Y chromosome patients (48 of whose partners suffered from RSA or early embryo growth arrest), 7 small Y chromosome patients, 106 other male patients whose partners had suffered from unexplained RSA or early embryo growth arrest, and 100 normal male controls were enrolled.
There was no fraction deletion of DYZ1 detected both in big Y patients and in normal men. Of RSA patients, 1 case showed deletion of 266bp from the gene locus 25-290bp, and 2 cases showed deletion of 773bp from 1347 to 2119bp. Of only 7 small Y chromosome patients, 2 cases showed deletion of 266bp from 25 to 290bp, and 4 cases showed deletion of 773bp from 1347 to 2119bp and 275bp from 3128 to 3420bp. The mean of DYZ1 copies was 3900 in normal control men; the mean in big Y patients was 5571, in RSA patients was 2655, and in small Y patients was 1059. All of the others were significantly different (P<0.01) compared with normal control men, which meant that DYZ1 copy number in normal control men was less than that of big Y chromosome patients, and was more than that of unexplained early RSA patients and small Y patients.
The integrity and copy number variation of DYZ1 are closely related to the Y chromosome length under microscope. The cause of RSA/early embryo growth arrest in some couples may be the increase (big Y patients) or decrease of DYZ1 copy number in the husbands' Y chromosome.
European journal of obstetrics, gynecology, and reproductive biology 08/2011; 159(2):371-4. · 1.97 Impact Factor
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Zi-Jiang Chen,
Han Zhao,
Lin He,
Yuhua Shi,
Yingying Qin,
Yongyong Shi,
Zhiqiang Li,
Li You,
Junli Zhao,
Jiayin Liu, [......],
Cuifang Hao,
Chun-E Ren,
Yajie Zhang,
Shiling Chen,
Wei Zhang,
Aijun Yang, Junhao Yan,
Yuan Li,
Jinlong Ma,
Yueran Zhao
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ABSTRACT: Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rs13405728; combined P-value by meta-analysis P(meta) = 7.55 × 10⁻²¹, odds ratio (OR) 0.71); 2p21 (rs13429458, P(meta) = 1.73 × 10⁻²³, OR 0.67); and 9q33.3 (rs2479106, P(meta) = 8.12 × 10⁻¹⁹, OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended.
Nature Genetics 01/2011; 43(1):55-9. · 35.53 Impact Factor
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ABSTRACT: This first large-scale report of birth defects in 15,405 offspring conceived by assisted reproductive technologies in China found infants born after IVF alone to have a birth defect frequency comparable to that in the general Chinese population; rates were nonsignificantly higher in infants conceived with use of intracytoplasmic sperm injection compared with those conceived after IVF alone.
Fertility and sterility 01/2011; 95(1):458-60. · 3.97 Impact Factor
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ABSTRACT: An association of polymorphism -1154G/A (rs1570360) in vascular endothelial growth factor (VEGF) gene with idiopathic recurrent spontaneous abortion (RSA) has been found in Caucasians. The aim of this study was to examine the association of VEGF -1154 with RSA in a well-defined group of Chinese Han patients.
The VEGF -1154G/A genotype was detected by real-time PCR with TaqMan probes. The products were also subjected to gene sequence analysis to validate the PCR results.
The allele frequencies of VEGF -1154G/A showed no significant difference between RSA patients and the normal controls (P = 0.183). The frequencies of VEGF -1154G/A genotypes were not significantly different between RSA patients and the normal controls (P = 0.228).
Our study revealed that VEGF -1154G/A polymorphism was not associated with the susceptibility to RSA in Chinese Han women.
American Journal Of Reproductive Immunology 10/2010; 65(5):521-5. · 2.17 Impact Factor
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ABSTRACT: The concerns over xenogeneic pathogens and immunogenic molecules derived from mouse embryonic fibroblasts (MEFs) trigger the development of human-derived feeder layers for human embryonic stem cell (hESC) maintenance. It is essential to evaluate the capability of these human feeder layers to retain the stemness and pluripotency of hESCs. In the present study, two Chinese hESC lines, SDU-hESCm-1 and SDU-hESCm-2, were continuously cultured on human adult uterine endometrial cells (hUEC), human fetal trophonema matrix cells (hFTMC), and MEFs for at least two month (up to 10 passages). A side-by-side comparison of the abilities to support: (1) self-renewal of the hESCs, (2) expression of undifferentiated markers, and (3) neural differentiation, was made between the human and mouse feeder layers. We demonstrated that the hESCs maintained on hUEC and hFTMC exhibited significantly higher growth rates and generated higher levels of DNA content than those on MEFs. Under neural differentiation-promoting conditions, greater neural differentiation was found in the hESCs maintained on human than on mouse feeder layers. These results suggest that human feeder layers derived from hUECs and hFTMCs are more efficient in supporting a long-term growth and neural differentiation of hESCs than MEFs.
Cellular reprogramming. 06/2010; 12(3):295-303.
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ABSTRACT: To examine abnormal fertilization phenomena in blastomeres of embryos generated from conventional IVF and ICSI displaying a single pronucleus at the zygote stage.
132 embryos from monopronuclear zygotes (1PN) generated from conventional IVF and ICSI were examined by FISH (fluorescent in situ hybridization) with X, Y dual color centromere probes.
In the embryos that were obtained from conventional IVF, the percentage of diploid, monoploid and mosaic sex chromosome were 54.35, 23.91 and 21.74%, respectively. In the embryos from 1PN zygotes derived from ICSI, the percentage of diploid, monoploid and mosaic sex chromosomes were 31.51, 31.51 and 36.99%, respectively. For monoploid embryos, the ratio of XO was significantly higher than that of YO in both conventional IVF and ICSI groups.
The results demonstrated that the majority of embryos derived from 1PN zygotes generated with conventional IVF or ICSI have a high incidence of aneuploidy. Furthermore, the sex chromosome diploid ratio of embryos from 1PN zygotes derived from conventional IVF was significantly higher than those generated from ICSI procedure in Chinese women. Nevertheless, the high proportion of aneuploid embryos suggests that such embryos should not be utilized for embryo transfer.
Gynecologic and Obstetric Investigation 10/2009; 69(1):20-3. · 1.28 Impact Factor
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ABSTRACT: No statistically significant differences in genotype and allele frequencies of single nucleotide polymorphism (SNP) rs13266634 in gene SLC30A8 were found between patients with polycystic ovary syndrome (PCOS) and healthy controls. No associations were observed between genotype of rs13266634 and the quantitative clinical features of PCOS patients in the PCOS group after adjustment for body mass index.
Fertility and sterility 01/2009; 91(4 Suppl):1598-601. · 3.97 Impact Factor
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ABSTRACT: To analyze the clinical and metabolic characteristics of large-scale Chinese women with polycystic ovary syndrome (PCOS).
Retrospective study.
Hospital-based IVF center.
Patients with PCOS.
In the present study, one thousand and forty PCOS patients were selected from women who visited the Reproductive Medicine Center at Shandong Provincial Hospital Shandong University between January 2002 and December 2006. All the patients had been performed a 75 g OGTT. Clinical characteristics, serum hormonal levels, glucose levels, insulin levels and lipid profiles were reviewed.
An oral glucose tolerance test and insulin release test were performed for each woman. After overnight fasting, blood samples were collected to determine fasting blood glucose, blood glucose and insulin (30 min, 60 min, 120 min, 180 min) after digesting 75 g glucose, luteotrophic hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), prolactin (PRL), estradiol (E2), and blood lipid levels.
Height, weight, waistline, hip circumference, F-G grade for hirsutism, gonadal hormone results, blood lipid level, blood glucose tolerance, each-moment insulin level, and family history were determined.
(i) The presence of oligomenorrhea was 62.6% while amenorrhea was 19.71%. Menstrual disorder of all the adult patients could be traced back to their adolescent menarche. There were 450 obesity cases of which 259 patients were central obesity. The incidence of acanthosis nigricans was 15.19%, 65.19% with obesity. (ii) Cholesterol (4.8 +/- 0.98 vs 4.61 +/- 0.86) and LDL (3.80 +/- 6.92 vs 2.88 +/- 1.01) were both significantly higher in the obesity patients than the non obesity patients. (iii) 173 patients were diagnosed as diabetes mellitus (DM), 179 IGT, 27 IFG and 9 (IFG and IGT). Those women with plasma glucose values abnormality of 0, 30 min, 60 min, 120 min, 180 min were 19 cases 0.98% (19/173), 74 cases 42.77% (74/173), 110 cases 63.58% (110/173), 42 cases 24.28% (42/173) and 12 cases 6.94% (12/173) respectively. Ten (10/173) patients would have been undetected if fasting plasma glucose levels were not evaluated, while omission of 30 min, 60 min, 120 min, or 180 min plasma glucose levels would have resulted in 16 cases (16/173), 50 cases (50/173), 28 cases (28/173) and 1 case (1/173) being missed respectively. If we took three times blood samples to evaluate plasma glucose levels, 39 cases (39/173) (0 min + 30 min +60 min), 102 cases (0 min + 30 min + 120 min), 21 cases (0 min + 30 min + 180 min), 34 cases (0 min + 60 min + 120 min), 45 cases (0 min + 60 min + 180 min), 123 cases (0 min + 120 min + 180 min) would be missed. Compared AUC of plasma glucose and insulin in 5 times with 3 times (0 min + 30 min + 60 min), the differences were statistically significant. Body mass index (BMI) was positively correlated with HOMA-IR (r = 0.29987 (P<0.01) as well as WHR (r = 0.12441, P<0.0001).
(i) The prevalence rate of obesity was higher in PCOS. The state of obesity had a positive relation with insulin resistance. (ii) The prevalence rate of lipid profiles abnormality in obesity group was higher than in non-obesity. (iii) OGTT was the essential examination for all the PCOS patients.
Neuro endocrinology letters 12/2007; 28(6):807-10. · 1.30 Impact Factor
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ABSTRACT: In order to further understand the role of fibrillin-1 (FBN1, OMIM 134797) perturbations in the pathogenesis of Marfan syndrome (MFS, OMIM 154700) we studied a Han Chinese family in which MFS was segregating. In the Chinese family with 5 affected members, mutation screening for FBN1 was performed using direct sequencing. A novel non-synonymous mutation in the transforming growth factor beta binding protein-like (TB) domain of the FBN1 gene was found. The missense mutation c.3022T>C (C1008R) located in exon 24. This mutation was present in the proband and in two other affected family members, but in neither unaffected family members nor unrelated control subjects. The novel non-synonymous mutation, c.3022T>C (C1008R) in the TB domain of FBN1 gene, may be involved in the pathogenesis of MFS in a Han Chinese family.
Neuro endocrinology letters 10/2007; 28(5):629-32. · 1.30 Impact Factor
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ABSTRACT: The objective was to examine the separation of X- and Y-bearing spermatozoa in a modified swim-up procedure using fluorescent in situ hybridization (FISH), and to find out the influence of swim-up time on the ratio of X- and Y-bearing spermatozoa.
Prospective study.
Reproductive testing laboratory in a university hospital.
Normal spermatozoa samples were obtained from 10 volunteers by masturbation after sexual abstinence for 3-5 days.
Spermatozoa were put into 18 tubes with 0.25 ml in each, then mixed with HTF medium and centrifuged for 5 min (400 x g). The supernatant was removed and discarded and 0.5 ml HTF was added slowly along the tube wall. Motile spermatozoa were collected after swimming up in different times (from 5 up to 150 min, with a total of 17 intervals). The X- and Y-bearing spermatozoa were determined using the FISH technique. The X/Y dual-color CEP probes that were marked by fluorescein isothiocyanate (FITC) and Texas red were applied to analyze the ratio of X- and Y-bearing spermatozoa. The FISH staining slides were analyzed under an immunofluorescence microscope. About 1000-1500 spermatozoa were counted per slide.
The percentages of X- and Y-bearing spermatozoa were calculated.
The study results suggested that the total ratio of hybridization was 98.33%. The ratio of X-bearing spermatozoa after swimming up for different amounts of time is 50.03 +/- 0.91% at 0 min, 50.45 +/- 2.06% after 15 min, 50.61 +/- 2.47% after 30 min, 50.16 +/- 2.67% after 60 min, 50.72 +/- 2.64% after 90 min, and 50.56 +/- 2.20% after 150 min. The statistical analysis showed that there were no significant differences among different swim-up times in the ratio of X-bearing spermatozoa.
There was no significant effect of swim-up time on the ratios of X- and Y-bearing spermatozoa using a modified swim-up procedure. No direct evidence was found that the swim-up procedure for separating motile spermatozoa to use for either intrauterine insemination (IUI) or in vitro fertilization (IVF) would lead to an imbalance of boys and girls.
European Journal of Obstetrics & Gynecology and Reproductive Biology 01/2007; 129(2):150-4. · 1.97 Impact Factor
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ABSTRACT: This study demonstrates that the diploid ratio of tripronuclear zygotes after intracytoplasmic sperm injection (ICSI) is significantly higher as compared with that after conventional IVF; the extra pronucleus of tripronuclear zygotes after ICSI are mostly from the second polar body, not from sperm.
Fertility and sterility 07/2005; 83(6):1845-8. · 3.97 Impact Factor
