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Wu Y.,Guangzhou University | Wu Y.,Key Laboratory of Reproductive Medicine of Guangdong Province | Wu Y.,Key Laboratory for Major Obstetric Diseases of Guangdong Province | Wu Y.,Higher Education Institutes | And 4 more authors.

Although the adverse effects of maternal aging on reproductive outcomes have been investigated widely, there is no consensus on the impact of paternal age. Therefore, we investigated the effect of paternal age on reproductive outcomes in a retrospective analysis of 9,991 in vitro fertilization (IVF) cycles performed at the Reproductive Medicine Center of the Third Affiliated Hospital of Guangzhou Medical University (China) between January 2007 and October 2013. Samples were grouped according to maternal age [<30 (3,327 cycles), 30-34 (4,587 cycles), and 35-38 (2,077 cycles)] and then subgrouped according to paternal age (<30, 30-32, 33-35, 36-38, 39-41, and ≥42). The groups did not differ in terms of fertilization rate, numbers of viable and high-quality embryos and miscarriage rate when controlling maternal age (P >0.05). Chi-squared analysis revealed that there were no differences in implantation and pregnancy rates among the different paternal age groups when maternal age was <30 and 35-38 years (P >0.05). However, implantation and pregnancy rates decreased with paternal age in the 31-34 y maternal age group (P <0.05). Our study indicates that paternal age has no impact on fertilization rate, embryo quality at the cleavage stage and miscarriage rate. For the 30-34 y maternal age group, the implantation rate decreased with increased paternal age, with the pregnancy rate in this group being significantly higher in the paternal <30 y and 30-32 y age groups, compared with those in the 36-38 y and 39-41 y groups. Copyright: © 2015 Wu et al. Source

Wu Y.,Guangzhou University | Wu Y.,Key Laboratory of Reproductive Medicine of Guangdong Province | Wu Y.,Key Laboratory for Major Obstetric Diseases of Guangdong Province | Wu Y.,Guangdong Higher Education Institutes | And 5 more authors.

The impact of paternal age on reproduction, especially using assisted reproductive technologies, has not been well studied to date. To investigate the effect of paternal age on reproductive outcomes, here we performed a retrospective analysis of 2,627 intracytoplasmic sperm injection (ICSI) cycles performed at the Reproductive Medicine Center of the Third Affiliated Hospital of Guangzhou Medical University (China) between January 2007 and May 2015. Effect of paternal age on embryo quality [number of fertilized oocytes 2 pronucleus zygotes (2PNs), viable embryos, and high-quality embryos] was analyzed by multiple linear regression. Relationships between paternal age and pregnancy outcomes were analyzed by binary logistic regression. After adjusting for female age, no association between paternal age and the following parameters of embryo quality was observed: number of fertilized oocytes (B = -0.032; 95% CI -0.069-0.005; P = 0.088), number of 2PNs (B = -0.005; 95% CI -0.044-0.034; P = 0.806), and number of viable embryos (B = -0.025; 95% CI -0.052-0.001; P = 0.062). However, paternal age negatively influenced the number of highquality embryos (B = -0.020; 95% CI -0.040-0.000; P = 0.045). Moreover, paternal age had no effect on pregnancy outcomes (OR for a 5-year interval), including the rates of clinical pregnancy (OR 0.919; 95% CI 0.839-1.006; P = 0.067), ongoing pregnancy (OR 0.914; 95% CI 0.833-1.003; P = 0.058), early pregnancy loss (OR 1.019; 95% CI 0.823-1.263; P = 0.861), live births (OR 0.916; 95% CI 0.833-1.007; P = 0.070), and preterm births (OR 1.061; 95% CI 0.898-1.254; P = 0.485). Therefore, increased paternal age negatively influences the number of high-quality embryos, but has no effect on pregnancy outcomes in couples undergoing ICSI cycles. However, more studies including men aged over 60 years with a longer-term follow-up are needed. Copyright © 2016 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source

Li W.,Sun Yat Sen University | Li W.,Key Laboratory of Reproductive Medicine of Guangdong Province | Huang L.,Sun Yat Sen University | Lin W.,Sun Yat Sen University | And 13 more authors.

Neural crest stem cells (NCSCs), a population of multipotent cells that migrate extensively and give rise to diverse derivatives, including peripheral and enteric neurons and glia, craniofacial cartilage and bone, melanocytes and smooth muscle, have great potential for regenerative medicine. Non-human primates provide optimal models for the development of stem cell therapies. Here, we describe the first derivation of NCSCs from cynomolgus monkey embryonic stem cells (CmESCs) at the neural rosette stage. CmESC-derived neurospheres replated on polyornithine/laminin-coated dishes migrated onto the substrate and showed characteristic expression of NCSC markers, including Sox10, AP2α, Slug, Nestin, p75, and HNK1. CmNCSCs were capable of propagating in an undifferentiated state invitro as adherent or suspension cultures, and could be subsequently induced to differentiate towards peripheral nervous system lineages (peripheral sympathetic neurons, sensory neurons, and Schwann cells) and mesenchymal lineages (osteoblasts, adipocytes, chondrocytes, and smooth muscle cells). CmNCSCs transplanted into developing chick embryos or fetal brains of cynomolgus macaques survived, migrated, and differentiated into progeny consistent with a neural crest identity. Our studies demonstrate that CmNCSCs offer a new tool for investigating neural crest development and neural crest-associated human disease and suggest that this non-human primate model may facilitate tissue engineering and regenerative medicine efforts. © 2014 Elsevier Ltd. Source

Yang Y.,Sun Yat Sen University | Yang Y.,Wayne State University | Xu Y.,Sun Yat Sen University | Xu Y.,Key Laboratory of Reproductive Medicine of Guangdong Province | And 13 more authors.
Journal of Assisted Reproduction and Genetics

Purpose: The objective of this study is to investigate the effect of 2, 5, and 20 % O2 on post-thaw day 3 human embryo culture until blastocyst stage. Methods: One hundred fifty-five day 3 human embryos were used. One hundred twenty out of 155 embryos were recovered after thawing. Surviving embryos were distributed into 2, 5, or 20 % O2 groups and cultured for 2.5 days. At the end of culture, blastocyst formation was assessed, and then, embryos were collected for RT-qPCR or immunofluorescence analysis. Results: Using visible blastocoel to define blastocyst formation, 58.7 % (27/46) of surviving day 3 embryos formed blastocyst at 2 % O2, 63.6 % (28/44) at 5 % O2, and 66.7 % (20/30) at 20 % O2. The difference in blastocyst formation rates was not significant. Average blastocyst cell number was 119.44 ± 11.64 at 2 % O2, 142.55 ± 22.47 at 5 % O2, and 97.29 ± 14.87 at 20 % O2. Average apoptotic rate was 4.7 % ± 0.4 % for blastocyst formed at 2 % O2, 3.5 % ± 0.7 % at 5 % O2, and 5.8 % ± 1.1 % at 20 % O2. Apoptosis rate was significantly lower for blastocysts formed at 5 % O2 (p < 0.05). Compared with gene expression levels at 5 % O2, which were arbitrarily set as “1,” 20 % O2 is associated with significantly higher expression of BAX (2.14 ± 0.47), G6PD (2.92 ± 1.06), MnSOD (2.87 ± 0.88), and HSP70.1 (8.68 ± 4.19). For all genes tested, no significant differences were found between 2 and 5 % O2. Conclusion: The result suggests that development of cryopreserved human embryos from day 3 to blastocyst stage benefits from culture at 5 % O2. © 2016 Springer Science+Business Media New York Source

Feng X.,Sun Yat Sen University | Luo Z.,Sun Yat Sen University | Jiang S.,Sun Yat Sen University | Li F.,Sun Yat Sen University | And 11 more authors.
Journal of Cell Science

The majority of cancer cells rely on elevated telomerase expression and activity for rapid growth and proliferation. Telomerase-negative cancer cells, by contrast, often employ the alternative lengthening of telomeres (ALT) pathway to maintain telomeres. ALT cells are characterized by long and dynamic telomeres and the presence of ALT-associated promyelocytic leukemia (PML) bodies (APBs). Previous work has shown the importance of APBs to the ALT pathway, but their formation and precise role remain unclear. Here, we demonstrate that a homeobox-containing protein known as HMBOX1 can directly bind telomeric double-stranded DNA and associate with PML nuclear bodies. Hence, we renamed this protein TAH1 for telomere-associated homeobox-containing protein 1. TAH1 knockdown significantly reduced the number of APBs and led to an increase in DNA damage response signals at telomeres. Importantly, TAH1 inhibition also notably reduced the presence of telomere C-circles, indicating altered ALT activity. Our findings point to TAH1 as a novel link between pathways that regulate DNA damage responses, PML nuclear bodies, and telomere homeostasis in ALT cells, and provide insight into how ALT cells may achieve sustained growth and proliferation independent of the telomerase. © 2013. Published by The Company of Biologists Ltd. Source

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