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Wang Q.,Sun Yat Sen University | Wang Q.,Guangdong Provincial Key Laboratory of Reproductive Medicine | Luo L.,Sun Yat Sen University | Luo L.,Guangdong Provincial Key Laboratory of Reproductive Medicine | And 11 more authors.
Reproductive BioMedicine Online | Year: 2016

A prospective cohort study was conducted to determine whether chromosome aneuploidy increases the risk of early spontaneous abortions in patients with polycystic ovary syndrome (PCOS). A total of 1461 patients who conceived after IVF and embryo transfer were followed; 100 patients who had experienced clinical spontaneous abortion were recruited, 32 with PCOS and 68 without PCOS. Before 2013, genetic analysis comprised conventional cultured villus chromosome karyotyping and a multiplex ligation-dependent probe amplification subtelomere assay combined with fluorescence in-situ hybridization; since 2013, array-based comparative genomic hybridization technique combined with chromosome karyotyping has been used. Age, BMI, pregnancy history, gestational age and total gonadotrophin dosage did not differ significantly between the PCOS and non-PCOS groups. In the PCOS group, 28.1% of abortuses demonstrated aneuploidy, which was significantly lower (P = 0.001) than in the non-PCOS group (72.1%). Further statistical analyses controlling for maternal age demonstrated that abortuses of women with PCOS were significantly less (P = 0.001) likely to have chromosome aneuploidy. Embryonic aneuploidy does not play a vital role in early spontaneous abortion in women with PCOS. Maternal factors resulting in endometrial disorders are more likely to be responsible for the increased risk of early spontaneous abortion in patients with PCOS. © 2016 Reproductive Healthcare Ltd.

Xu Y.,Sun Yat Sen University | Xu Y.,Guangdong Provincial Key Laboratory of Reproductive Medicine | Chen S.,BGI Shenzhen | Chen S.,Shenzhen Municipal Key Laboratory of Birth Defects Screening and Engineering | And 30 more authors.
Clinical Chemistry | Year: 2015

BACKGROUND: The embryonic genome, including genotypes and haplotypes, contains all the information for preimplantation genetic diagnosis, representing great potential for mendelian disorder carriers to conceive healthy babies. METHODS: We developed a strategy to obtain the full embryonic genome for a β-thalassemia-carrier couple to have a healthy second baby. We carried out sequencing for single blastomere cells and the family trio and further developed the analysis pipeline, including recovery of the missing alleles, removal of the majority of errors, and phasing of the embryonic genome. RESULTS: The final accuracy for homozygous and heterozygous single-nucleotide polymorphisms reached 99.62% and 98.39%, respectively. The aneuploidies of embryos were detected as well. Based on the comprehensive embryonic genome, we effectively performed whole-genome mendelian disorder diagnosis and human leukocyte antigen matching tests. CONCLUSIONS: This retrospective study in a β-thalassemia family demonstrates a method for embryo genome recovery through single-cell sequencing, which permits detection of genetic variations in preimplantation genetic diagnosis. It shows the potential of single-cell sequencing technology in preimplantation genetic diagnosis clinical practices. © 2015 American Association for Clinical Chemistry.

Xiao G.,University of South China | Xiao G.,Guangzhou University | Xiao G.,Guangdong Provincial Key Laboratory of Reproductive Medicine | Xia C.,Guangzhou University | And 15 more authors.
PLoS ONE | Year: 2014

Infertility is an area of increasing in life science research. Although follicular maturation disorders and anovulation are the primary causations of infertility, its molecular mechanism is not well understood. Recent research has shown that microRNAs (miRNAs) might play an important role in the regulation of ovarian follicle development and maturation. In this study, the expression of miRNAs in metaphase I (MI) oocytes treated with or without insulin-like growth factor 1 (IGF-1) was observed by microRNA microarray analysis. Results show that 145 miRNAs were up-regulated and 200 miRNAs were downregulated in MI oocytes after IGF-1 treatment. MiR-133b, which was up-regulated more than 30-fold, was chosen for further research. As a potential target of miR133b, transgelin 2 (TAGLN2) gene was down-regulated, at both transcription and translation levels, in miR-133b- over-expressed 293T cells, but TAGLN2 was up-regulated when the expression of miR-133b was inhibited. Furthermore, the expression level of TAGLN2 in the ovaries of 8-week- old mice was higher than that observed in 4-week-old mice. Immunofluorescence experiments showed that TAGLN2 was located in the cytoplasm. In general, our results indicate that miR-133b may play important roles in the growth and maturation of oocytes by regulating its potential target, TAGLN2, at both transcription and translation levels. Therefore, our research provides a potential new target for infertility therapy. © 2014 Xiao et al.

Yang J.,University of South China | Yang J.,Guangzhou University | Yang J.,Guangdong Provincial Key Laboratory of Reproductive Medicine | Zhong T.,Guangzhou University | And 15 more authors.
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2015

Objectives Transforming growth factor-beta 1 (TGF-β1) is one of the multifunctional cytokine families. It takes part in a series of physiological and pathological processes in the human body, including wound healing, tissue fibrosis and embryonic development. Recent studies have shown that TGF-β1 participates in the development of polycystic ovary syndrome (PCOS). This study was therefore designed to investigate the association of TGF-β1 polymorphism with the risk of PCOS. Study design We enrolled 328 PCOS patients and 358 healthy individuals in this study. Five single nucleotide polymorphisms (SNPs) - rs4803457C/T, rs11466313 deletion/AGG, rs2217130C/T, rs1800469C/T and rs1800470C/T - were detected using Snapshot technology. Linkage disequilibrium and haplotype analysis was conducted among the five SNPs. The relationship between genotypes and haplotypes and the risk of PCOS was also explored. Results The TT/CT/CC genotype frequencies of rs4803457 in the PCOS group and the control group were 0.2805/0.4878/0.2317 and 0.3659/0.4749/0.1592 respectively. The C/T allele frequencies in the PCOS group and control group were 0.3813/0.6187 and 0.3966/0.6034 respectively. There were significant differences in genotype distribution frequencies and allele frequencies between these two groups (P = 0.018). Logistic regression analysis showed that CC genotype had higher risk of PCOS than the no CC genotype in rs4803457 loci (OR = 1.75, 95%CI = 1.11-2.75). Haplotype analysis further showed that the haplotypes "T-del-C-C-C", "C-del-C-C-C" and "C-del-C-T-C" were associated with the highest risk of PCOS. However, for rs11466313 deletion/AGG, rs2217130C/T, rs1800469C/T and rs1800470C/T, no significant association with PCOS risk was observed. Conclusion The TGF-β1 gene rs4803457C/T polymorphism is associated with susceptibility to PCOS, and is the key contributor for the development of PCOS in Chinese Han women. The haplotypes T-del-C-C-C, C-del-C-C-C and C-del-C-T-C are also risk factors for PCOS susceptibility among Chinese Han women. © 2014 Elsevier Ireland Ltd. All rights reserved.

Xu J.,Reproductive Medicine Center | Xu J.,Sun Yat Sen University | Xu J.,Guangdong Provincial Key Laboratory of Reproductive Medicine | Xu Y.,Sun Yat Sen University | And 10 more authors.
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2015

Objective To investigate whether the expression patterns of periphery clock genes were influenced by menstrual cycle in a monkey model. Study design In this preliminary study, the expression patterns of four clock genes (Bmal1, Clock, Cry1 and Per2) in peripheral blood mononuclear cells (PBMCs) from 6 female Macaca fascicularis in menstrual, late follicular and mid luteal phases of menstrual cycle were determined by qrt-PCR. Results Bmal1 and Per2 mRNA levels were found to exhibit significant diurnal rhythms in all phases of the menstrual cycle. The expression of Cry1 mRNA was statistically rhythmic in late follicular and mid luteal phases. A main effect of menstrual cycle existed on the rhythms of Bmal1, Cry1 and Per2 expression, but not Clock expression. No significant differences were detected between menstrual phase and late follicular phase in all clock genes. Significant differences were found on the expression of Bmal1, Cry1 or Per2 mRNA between late follicular phase and mid luteal phase, when no difference existed in estrogen level, indicating the role of progesterone on biological clock gene expression. Furthermore, the peak of Bmal1 mRNA level slightly advanced in mid luteal phase compared with that in menstrual and late follicular phases. Conclusion The expression patterns of clock genes in PBMCs were influenced by menstrual cycle, potentially by the change of progesterone levels, and this effect maybe correlated with early pregnancy. © 2015 Elsevier Ireland Ltd. All rights reserved.

Xia C.,Guangzhou University | Cai Y.,Foshan Maternity and Child Heath Care Hospital | Li S.,Guangzhou University | Yang J.,Guangzhou University | And 3 more authors.
Neurochemical Research | Year: 2015

Neuronal cell dysfunction and apoptosis are the main causes of the invasion of the central nervous system by human immunodeficiency virus type 1 (HIV-1), although the underlying mechanism has not been well understood. Recent research has shown that curcumin might play an important role in regulating HIV-1 development. Heat shock protein 70 (HSP70), a protein induced by heat, was reported to inhibit apoptosis through various cell signaling pathways in brain. Overexpression of HSP70 could effectively protected neurons in many animal and cellular models of dementia. In the present study, the expression of HSP70 in the gp120 V3 loop peptide-induced neuronal apoptosis was investigated. Our results demonstrated that gp120 V3 loop peptide could induce primary rat cortical neuronal apoptosis. We also found that curcumin could increase HSP70 expression. In addition, the expression level of both HSP70 mRNA and HSP70 protein were dependent on the curcumin dose in the rat cortical neurons. Curcumin could improve HSP70 expression in gp120 V3 loop peptide-induced primary rat cortical neuronal apoptosis. In general, our results indicated that curcumin played an important role in the gp120 V3 loop peptide induced neuronal apoptosis by regulating HSP70. © 2015, Springer Science+Business Media New York.

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