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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. Source

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. Source

Li M.,Peking University | Li M.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology | Yu Y.,Peking University | Yu Y.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology | And 15 more authors.
PLoS ONE | Year: 2012

It is important to identify effective contraceptive drugs that cause minimal disruption to physiological processes. Phosphodiesterase 3 (PDE3) inhibitors suppress meiosis in oocytes by decreasing the level of cAMP and blocking the extrusion of the first polar body. In this study, we tested the PDE3 inhibitor, cilostazol, as a potential contraceptive agent. The effects of cilostazol treatment in vitro and in vivo on the suppression of oocyte maturation in a mouse model were investigated. The results indicated that treatment with increasing concentrations of cilostazol led to a dose-dependent arrest in meiosis progression. The effective in vitro concentration was 1 μM and was 300 mg/kg in vivo. The effect of cilostazol was reversible. After removal of the drug, meiosis resumed and mouse oocytes matured in vitro, and showed normal chromosome alignment and spindle organization. After fertilization using an ICSI method, the oocytes showed normal morphology, fertilization rate, embryo cleavage, blastocyst formation, and number of viable pups when compared with controls. The offspring showed similar body weight and fertility. In vivo, the mice became infertile if the drug was injected sequentially, and became pregnant following discontinuation of cilostazol. More importantly, no side effects of cilostazol were observed in treated female mice as demonstrated by blood pressure and heart rate monitoring. It is concluded that cilostazol, a drug routinely used for intermittent claudication, can effectively inhibit oocyte maturation in vitro and in vivo, does not affect the developmental potential of oocytes following drug removal and has few side effects in female mice treated with this drug. These findings suggest that cilostazol may be a potential new contraceptive agent that may facilitate an efficacy and safety study of this drug. © 2012 Li et al. Source

Yu Y.,Peking University | Yu Y.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology | Yu Y.,Key Laboratory of Assisted Reproduction | Zhao Y.,Peking University | And 11 more authors.
Journal of Proteome Research | Year: 2013

Preimplantation genetic diagnosis (PGD) is important for screening genetic and chromosome mutations in embryos so that the efficiency of assisted reproductive treatment can be increased and birth defects can be decreased; however, some studies have reported a risk from this technology as well as other assisted reproductive technologies. We have developed a blastomere biopsy mouse model to assess the potential effects of blastomere biopsy that was one key procedure in PGD on the fertility of female mice at different ages. We showed that female fertility was decreased in the biopsied mouse model with an increase in age. Moreover, the ovarian weight, serum hormone levels, and the number of primordial, primary, preantral, and antral stage follicles were also decreased in the middle-aged biopsied mouse model. To elucidate the underlying molecular mechanism, we did proteomics analysis on ovarian tissues from puberty biopsied and nonbiopsied mice of the 23 differentially expressed proteins that were screened for in both groups, 3 proteins (PSMB8, ALDH1A1, and HSPA4) were selected and identified by Western blotting and quantitative RT-PCR methods, which showed the 3 proteins to regulate 12 cellular pathways. Furthermore, these three proteins were shown to be located in ovarian tissues, and the dynamic changes of expression profiling in middle-aged biopsied and nonbiopsied mice were demonstrated. The present study showed that blastomere biopsy technology impairs fertility when mice are middle-aged, which possibly resulted in abnormal expression profiling of PSMB8, ALDH1A1, and HSPA4 proteins. Thus, additional studies should be performed to assess the overall risk of blastomere biopsies during PGD procedures. © 2013 American Chemical Society. Source

Fan Y.,Guangzhou University | Li R.,Peking University | Li R.,Key Laboratory of Assisted Reproduction | Huang J.,Peking University | And 11 more authors.
Stem Cells and Development | Year: 2014

Human embryonic stem cells (hESCs) hold great promise for future clinical cell therapies because of their unique potential to differentiate into all human cell types. However, the destruction of normal fertilized embryos and the derivation of hESCs for research has resulted in polarized ethical debates, with most of the controversy centered on embryo destruction. Therefore, due to less ethical controversy surrounding them, abnormal fertilized zygotes that are usually discarded are a potential feasible resource for the derivation of hESCs. Microsurgery on human polyspermic zygotes can contribute to the derivation of hESCs, but the efficiency is much lower. Here, we reported a culture system to enhance the developmental competence of such microsurgical human polyspermic zygotes by EGF-BDNF-IGF-1 combination, which eventually resulted in the increased derivation efficiency of hESCs from them. We found that the developmental efficiency of microsurgical enucleated tripronuclear (3PN) embryos cultured with the EGF-BDNF-IGF-1 combination was significantly increased compared with the control group. More importantly, when the microsurgical enucleated 3PN embryos were cultured in medium supplemented with EGF-BDNF-IGF-1, the frequency ratio of chromosome abnormality was reduced. Our present study will facilitate the development of hESC line derivation in subsequent studies and also provide an additional choice for infertile couples. © Mary Ann Liebert, Inc. 2014. Source

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