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Fan Y.,Guangzhou University | Li R.,Peking University | Huang J.,Peking University | Yu Y.,Peking University | And 4 more authors.
Cell Cycle | Year: 2013

Human embryonic stem cells have shown tremendous potential in regenerative medicine, and the recent progress in haploid embryonic stem cells provides new insights for future applications of embryonic stem cells. Disruption of normal fertilized embryos remains controversial; thus, the development of a new source for human embryonic stem cells is important for their usefulness. Here, we investigated the feasibility of haploid and diploid embryo reconstruction and embryonic stem cell derivation using microsurgically repaired tripronuclear human zygotes. Diploid and haploid zygotes were successfully reconstructed, but a large proportion of them still had a tripolar spindle assembly. The reconstructed embryos developed to the blastocyst stage, although the loss of chromosomes was observed in these zygotes. Finally, triploid and diploid human embryonic stem cells were derived from tripronuclear and reconstructed zygotes (from which only one pronucleus was removed), but haploid human embryonic stem cells were not successfully derived from the reconstructed zygotes when two pronuclei were removed. Both triploid and diploid human embryonic stem cells showed the general characteristics of human embryonic stem cells. These results indicate that the lower embryo quality resulting from abnormal spindle assembly contributed to the failure of the haploid embryonic stem cell derivation. However, the successful derivation of diploid embryonic stem cells demonstrated that microsurgical tripronuclear zygotes are an alternative source of human embryonic stem cells. In the future, improving spindle assembly will facilitate the application of triploid zygotes to the field of haploid embryonic stem cells. © 2013 Landes Bioscience.

Qin Y.,Shandong University of Technology | Zhao H.,Shandong University of Technology | Xu J.,Fudan University | Shi Y.,Shanghai JiaoTong University | And 11 more authors.
Human Molecular Genetics | Year: 2012

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. © The Author 2011. Published by Oxford University Press. All rights reserved.

Zhao Y.,Peking University | Zhao Y.,Key Laboratory of Assisted Reproduction | Zhao Y.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology | Qiao J.,Peking University | And 2 more authors.
Steroids | Year: 2013

Polycystic ovary syndrome (PCOS) is the most common endocrine problem affecting women of reproductive age and is investigated from many regions of the world. Some reports have indicated ethnic difference in its manifestation. This review addressed the evidences for ethnic variation in the expression of PCOS phenotypes and explored the potential ethnic-specific diagnosis of this syndrome. To determine ethnic variation, community prevalence and clinical and metabolic problems, including hyperandrogenism, oligomenorrhoea/amenorrhoea, polycystic ovaries, obesity, insulin resistance and the metabolic syndrome, had been compared from differing backgrounds and populations. Moreover, a link between ethnicity and variation in the metabolic phenotype of PCOS had also been identified. East Asian women with PCOS have a lower BMI and a milder hyperandrogenic phenotype, but with the highest prevalence of metabolic syndrome. South Asians in particular have a high prevalence of insulin resistance and metabolic syndrome, and are at risk for type 2 diabetes, with central obesity more than BMI reflecting their metabolic risk. African American and Hispanic women are more obese and more prone to metabolic problems. Besides, there is a higher prevalence of hirsutism among women of Middle Eastern and Mediterranean origin. Ethnically appropriate guidelines are needed for identifying anthropometric thresholds for better screening and diagnosis in high-risk ethnic groups.

Hou Y.,Peking University | Fan W.,Peking University | Fan W.,Peking Tsinghua Center for Life science | Yan L.,Peking University | And 11 more authors.
Cell | Year: 2013

Single-cell genome analyses of human oocytes are important for meiosis research and preimplantation genomic screening. However, the nonuniformity of single-cell whole-genome amplification hindered its use. Here, we demonstrate genome analyses of single human oocytes using multiple annealing and looping-based amplification cycle (MALBAC)-based sequencing technology. By sequencing the triads of the first and second polar bodies (PB1 and PB2) and the oocyte pronuclei from same female egg donors, we phase the genomes of these donors with detected SNPs and determine the crossover maps of their oocytes. Our data exhibit an expected crossover interference and indicate a weak chromatid interference. Further, the genome of the oocyte pronucleus, including information regarding aneuploidy and SNPs in disease-associated alleles, can be accurately deduced from the genomes of PB1 and PB2. The MALBAC-based preimplantation genomic screening in in vitro fertilization (IVF) enables accurate and cost-effective selection of normal fertilized eggs for embryo transfer. PaperFlick © 2013 Elsevier Inc.

Lu Q.,Peking University | Lu Q.,Key Laboratory of Assisted Reproduction | Shen H.,Peking University | Shen H.,Key Laboratory of Assisted Reproduction | And 6 more authors.
Journal of Assisted Reproduction and Genetics | Year: 2014

Objective: To investigate the association of basal testosterone (T) levels with the outcome of in vitro fertilization (IVF) in women with diminished ovarian reserve (DOR). Methods: Complete clinical data on the first 223 IVF cycles in women with DOR were retrospectively analyzed. The associations of basal follicle stimulating hormone, luteinizing hormone, estradiol, and T levels with ovarian response and IVF outcome were studied. Results: Basal T levels were significantly different between pregnant and non-pregnant women. However, basal T levels showed no correlation with controlled ovarian hyperstimulation parameters after adjusting for age. The association of basal T levels with pregnancy rate was significant after adjusting for other impact factors. Using receiver operating characteristic (ROC) analysis, the basal T level of 1.115 nmol/L for predicting pregnancy outcome had a sensitivity of 82.80 % and specificity of 58.09 %. The women were divided into two groups based on this value; although the clinical characteristics and ovarian stimulation parameters were similar, the clinical pregnancy (16.18 % (11/68) vs. 40.15 % (53/132), respectively, p∈=∈0.000) and implantation rates (10.07 % (15/149) vs. 22.41 % (65/290), respectively, p∈=∈0.002) were significantly different in the low and high T level groups. Conclusion: In women with DOR, the basal T level presented a positive association with pregnancy outcome in IVF. The poor reproductive outcome observed in women with lower basal T levels may be due to the decreased implantation rate. © 2014 Springer Science+Business Media New York.

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