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Xue H.,Shandong University | Xue H.,Rizhao City Hospital of Traditional Chinese Medicine | Xue H.,National Research Center for Assisted Reproductive Technology and Reproductive Genetics | Xue H.,The Key Laboratory for Reproductive Endocrinology of Ministry of Education | And 15 more authors.
Journal of Assisted Reproduction and Genetics | Year: 2016

Purpose: The objective of this study was to evaluate the association between single-nucleotide polymorphisms (SNPs) rs2197076 and rs2241883 in fatty acid-binding protein 1 (FABP1) gene and polycystic ovary syndrome (PCOS). Methods: The two alleles rs2197076 and rs2241883 in FABP1 gene in 221 PCOS women and 198 normal women were amplified and sequenced. Allele frequency comparison was performed between the PCOS and control groups, and genotype-phenotype correlation analysis was performed using dominant and recessive models to assess the association of FABP1 and the main features of PCOS. Results: Allele frequency analyses showed a strong association of SNPs rs2197076 and rs2241883 of FABP1 gene with PCOS (P < 0.001). The additive, dominant, and recessive genotype model analyses further supported this association even after adjusting for age and body mass index (BMI). The minor allele frequency (MAF) of rs2241883 in obese PCOS women was less than that in obese control women. Further genotype-phenotype correlation analysis showed that SNP rs2197076 had a stronger association with the main features of PCOS than SNP rs2241883. Conclusion: In the association of SNPs in FABP1 gene with PCOS, rs2197076 was more closely associated with its main features than rs2241883 and seemed to play a more important role in the pathogenesis of PCOS. © 2015, Springer Science+Business Media New York.


Li T.,Shandong University | Li T.,National Research Center for Assisted Reproductive Technology and Reproductive Genetics | Wu K.,Shandong University | Wu K.,National Research Center for Assisted Reproductive Technology and Reproductive Genetics | And 36 more authors.
PLoS ONE | Year: 2013

Background:Fat mass and obesity-associated gene (FTO) has been associated with obesity, especially the common variant rs9939609. Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder and over 50% of patients are overweight/obese. Thus FTO is a potential candidate gene for PCOS but their relationship is confusing and remains to be clarified in different population with a large sample size. Method:This study was performed adopting a two-stage design by genotyping SNP rs9939609. The first set comprise of 741 PCOS and 704 control subjects, with data from our previous GWAS. The second phase of replication study was performed among another independent group of 2858 PCOS and 2358 control subjects using TaqMan-MGB probe assay. All subjects are from Han Chinese.Results:The less meaningful association of FTO rs9939609 and PCOS discovered in GWAS (P = 2.47E-03), was further confirmed in the replication study (P = 1.86E-09). Using meta-analysis, the P-meta value has reached 6.89E-12, over-exceeding the genome-wide association level of 5.00E-8. By combination, the P value was 1.26E-11 and after BMI adjustment it remained significant(P = 1.82E-06). To further elucidate whether this association is resulted from obesity or PCOS per se, the samples were divided into two groups-obese and non-obese PCOS, and the results were still positive in obese group (P obese = 5.81E-05, OR = 1.55), as well as in non-obese PCOS group (P non-obese = 7.06E-04, OR = 1.28).Conclusion:Variant rs9939609 in FTO is associated with PCOS in Chinese women, not only in obese PCOS subjects, but also in non-obese cases. © 2013 Li et al.


Yan L.,Shandong University | Yan L.,National Research Center for Assisted Reproductive Technology and Reproductive Genetics | Yan L.,The Key Laboratory for Reproductive Endocrinology of Ministry of Education | Li M.,Shandong University | And 19 more authors.
Gynecology and Minimally Invasive Therapy | Year: 2016

Study objective To investigate the impact of an ovarian dermoid cyst or dermoid cyst surgery on ovarian reserve in patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Design We performed a retrospective cohort study by using the records of patients with a history of ovarian dermoid cyst who underwent IVF/ICSI between 2009 and 2013. The antral follicle count (AFC) obtained by transvaginal ultrasound during controlled ovarian hyperstimulation of IVF/ICSI, total number of basal follicles [i.e., basal antral follicle count (B-AFC)], and dominant follicles greater than 1.4 cm [i.e., dominant antral follicle count (D-AFC)] were calculated between the different groups. Patients We included 260 patients with a history of dermoid cyst excision and 23 patients with a dermoid cyst who underwent IVF/ICSI. Two hundred and eighty-three matched patients without a dermoid cyst and ovarian surgery history were included. Intervention None. Measurements and main results The B-AFC was significantly smaller in the dermoid cyst group than in the matched control group (p = 0.030). The B-AFC and D-AFC were both significantly smaller for the previously operated ovary than for the contralateral nonoperated ovary (p = < 0.001), and both were smaller in the ovary with a teratoma than in the other teratoma-free ovary with a mean reduction of 40.5% and 38.8%, respectively (p = 0.018 and p = 0.004, respectively). The B-AFC and D-AFC were significantly fewer in ovaries treated by open surgery than in ovaries treated laparoscopically (p = 0.031 and p = 0.028, respectively). There was no significant difference in the main IVF outcomes between the two groups or the subgroups. Conclusion Our results suggest that ovarian dermoid cyst excision could significantly reduce ovarian reserve to a similar extent as the cyst itself. The presence or resection of dermoid cysts will not affect the main IVF outcomes. © 2016


Zhao H.,Shandong University | Zhao H.,National Research Center for Assisted Reproductive Technology | Zhao H.,The Key laboratory for Reproductive Endocrinology of Ministry of Education | Zhao H.,Shandong Provincial Key Laboratory of Reproductive Medicine | And 5 more authors.
Molecular Human Reproduction | Year: 2013

Many genetic association studies have been performed to investigate disorders of female reproduction, such as polycystic ovary syndrome, premature ovarian failure and endometriosis. These disorders typically manifest heterogeneously, and their pathogeneses are influenced by polygenic and environmental factors. Researchers evaluating these genetic associations have chosen candidate genes related to hormone action, steroid biosynthesis, inflammatory cytokines and autoimmune factors. Several of these genes have yielded statistically significant associations with female reproductive disorders; however, few associations have been robust and reproducible. Whole-genome association studies generate more reliable and unbiased results and represent a breakthrough in genetic studies of female reproduction. Nevertheless, to date only a very small fraction of the overall heritability has been identified and so further studies are needed. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Guo T.,Shandong University | Guo T.,National Research Center for Assisted Reproductive Technology | Guo T.,The Key Laboratory for Reproductive Endocrinology of Ministry of Education | Qin Y.,Shandong University | And 17 more authors.
International Journal of Andrology | Year: 2012

Chromosomal polymorphism has been reported to be associated with infertility, but its effect on IVF/ICSI-ET outcome is still controversial. To evaluate whether or not chromosomal polymorphism in men plays a role in spermatogenesis and the outcome of IVF/ICSI-ET, we retrospectively analysed 281 infertile couples. Measures included fertilization rate, implantation rate, pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, early miscarriage rate and preterm rate. Men with chromosomal polymorphism had significantly higher frequencies of severe oligozoospermia and azoospermia than those without (37.12% vs. 16.11%, p<0.001; 27.27% vs. 10.74%, p<0.001; respectively). Significantly, lower fertilization rate (68.02% vs. 78.00%, p<0.001) and clinical pregnancy rate (45.00% vs. 66.67%, p=0.031) were observed in polymorphism-carrying men with severe oligozoospermia compared with non-carriers with severe oligozoospermia. This suggests that chromosomal polymorphism has adverse effects on spermatogenesis, negatively influencing the outcome of IVF/ICSI-ET treatment. Polymorphic variations on the Y chromosome have been found to be the most prevalent polymorphism in infertile men, most frequently occurring in patients with severe oligozoospermia. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.


Zhao H.,Shandong University | Zhao H.,National Research Center for Assisted Reproductive Technology and Reproductive Genetics | Zhao H.,The Key Laboratory for Reproductive Endocrinology of Ministry of Education | Lv Y.,Shandong University | And 10 more authors.
Best Practice and Research: Clinical Obstetrics and Gynaecology | Year: 2016

Polycystic ovary syndrome (PCOS) is a highly heterogeneous reproductive system disorder of which the aetiology is not fully understood. Previous association studies have been conducted on >100 candidate genes, which principally related to reproductive hormones, cellular metabolism and chronic inflammation. Heritable tendencies have long been recognized for pathogeneses of PCOS, and recently a genome-wide association study (GWAS) in PCOS provides new clues to understand the genetic components and pathways in PCOS physiology. However, the current knowledge of the pathogenesis of PCOS is still in its infancy. Further studies using new technologies such as next-generation sequencing (NGS) shall be useful to understand more causal variants for PCOS. © 2016.


Li T.,Shandong University | Li T.,National Research Center for Assisted Reproductive Technology | Li T.,The Key laboratory for Reproductive Endocrinology of Ministry of Education | Li T.,Shandong Provincial Key Laboratory of Reproductive Medicine | And 29 more authors.
Journal of Medical Genetics | Year: 2012

Background: A previously reported genome-wide association study (GWAS) of polycystic ovary syndrome (PCOS) in Han Chinese found that several loci of p value around 10e-5 warrant investigation. Replication of the GWAS was applied in this study to determine whether gene YAP1 (yeast associated protein 1) is associated with PCOS. Methods: An independent set of 1115 PCOS patients and 1137 controls were recruited; single nucleotide polymorphisms (SNPs) rs11225138, rs11225161, and rs11225166 from YAP1 were selected for the replication study. Real-time quantitative PCR was applied for genotyping by TaqMan-MGB probe assay. Results: Meta-analysis showed that the allele frequency of rs11225161 (A/G) was significantly different between PCOS and controls at a GWA significance (Pmeta =3.98e 09). Genotype-phenotype correlation study found 30 min and 60 min glucose of the oral glucose tolerance test were higher in PCOS patients with rs11225161 risk allele A. The G allele of SNP rs11225138 (G/C) was a further risk factor for higher luteinising hormone level in PCOS patients (p=0.041). Conclusion: YAP1 appears to be a new susceptibility gene for PCOS in Han Chinese women.


Zhang Q.,Shandong University | Zhang Q.,National Research Center for Assisted Reproductive Technology and Reproductive Genetics | Zhang Q.,The Key Laboratory for Reproductive Endocrinology of Ministry of Education | Zhang Q.,Shandong Provincial Key Laboratory of Reproductive Medicine | And 4 more authors.
Reproductive Medicine and Biology | Year: 2015

Embryonic development into an implantation-competent blastocyst, synchronized uterine transformation into a receptive stage, and an intimate cross-talk between the activated blastocyst and the receptive uterus are essential for successful implantation, and therefore for subsequent pregnancy outcome. Evidence accumulating during recent years has underlined the importance of the Wnt signaling pathway in mammalian implantation and decidualization. Herein, this review focuses on the current state of knowledge regarding Wnt signaling in multiple implantation and decidualization events: pre-implantation embryo development, blastocyst activation for implantation, uterine development, and decidualization. © 2015 Japan Society for Reproductive Medicine


Gu Y.,Shandong University | Bian Y.,Shandong University | Bian Y.,National Research Center for Assisted Reproductive Technology and Reproductive Genetics | Bian Y.,The Key Laboratory for Reproductive Endocrinology of Ministry of Education | And 27 more authors.
Placenta | Year: 2016

Objective Placenta accreta is defined as abnormal adhesion of placental villi to the uterine myometrium. Although this condition has become more common as a result of the increasing rate of cesarean sections, the underlying causative mechanism(s) remain elusive. Because microRNA-29a/b/c (miR-29a/b/c) have been shown to play important roles in placental development, this study evaluated the roles of these microRNAs in placenta accreta. Methods Expression of miR-29a/b/c and myeloid cell leukemia-1 (MCL1) were quantified in patient tissues and HTR8/SVneo trophoblast cells using the real-time quantitative polymerase chain reaction. Western blotting was used to analyze expression of the MCL1 protein in HTR8/SVneo trophoblast cells with altered expression of miR-29a/b/c. To determine their role in apoptosis, miR-29a/b/c were overexpressed in HTR-8/SVneo cells, and levels of apoptosis were analyzed by flow cytometry. Luciferase activity assays were used to determine whether MCL1 is a target gene of miR-29a/b/c. Results Expression of miR-29a/b/c was significantly lower in creta sites compared to noncreta sites (p = 0.018, 0.041, and 0.022, respectively), but expression of MCL1 was upregulated in creta sites (p = 0.039). MCL1 expression was significantly downregulated in HTR-8/SVneo cells overexpressing miR-29a/b/c (p = 0.002, 0.008, and 0.013, respectively). Luciferase activity assays revealed that miR-29a/b/c directly target the 3′ untranslated region of MCL1 in 293T cells. Over-expression of miR-29a/b/c induced apoptosis in the HTR-8/SVneo trophoblast cell line. Moreover, histopathological evaluation revealed that the number of implantation site intermediate trophoblast (ISIT) cells was increased in creta sites and that these cells were positive for MCL1. Conclusions Our results demonstrate that in placenta accreta, miR-29a/b/c inhibits apoptosis of ISIT cells by targeting MCL1. These findings provide new insights into the pathogenesis of placenta accreta. © 2016 Elsevier Ltd


Shanshan G.,Shandong University | Shanshan G.,National Research Center for Assisted Reproductive Technology and Reproductive Genetics | Shanshan G.,The Key Laboratory for Reproductive Endocrinology of Ministry of Education | Shanshan G.,Shandong Provincial Key Laboratory of Reproductive Medicine | And 20 more authors.
Journal of Assisted Reproduction and Genetics | Year: 2015

Purpose: To evaluate the effect of different exposure temperatures during the dilution process on the survival rate of vitrified oocytes and following development. Methods: Patients were divided at random into two groups for different dilution temperature (20–22 °C, RT group; 37 °C,37 °C group) according to computer-generated random numbers on the day of oocyte warming. The survival and fertilization rates of vitrified oocytes as well as the implantation and clinical pregnancy rates of the resulting embryos were recorded. Results: A total of 662 and 676 oocytes were warmed in the 37 °C group and RT group, respectively, and significant difference was observed in the survival rate between 37 °C group (88.37 %) and RT group (79.88 %) (P = 0.0000). There was significant difference between the survival rate of 37 °Cgroup (87.27 %) and RT group (75.64 %) in nondonor patients (P = 0.0001). Multiple linear regression analysis showed that dilution temperature (β = 0.079, P = 0.017) and clinical outcomes of fresh cycles (β = 0.063, P = 0.001) were significantly and independently associated with survival rate. No significant difference was found between the 37 °C group and RT group in: fertilization rate (66.67 versus 65.37 %), implantation rate (20.0 versus19.46 %), clinical pregnancy rate (37.5 versus 35.0 %). Conclusions: In conclusion, the results of this study give supportive evidence of the application of 37 °C in the dilution process, especially for oocytes of poor quality. Further studies with well-controlled experimental groups are needed to optimize protocols for human oocyte vitrification. © 2015, Springer Science+Business Media New York.

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