Chu D.-P.,Institute for Family Planning |
Chu D.-P.,Peking Union Medical College |
Tian S.,Haidian Maternal and Child Health Hospital |
Qi L.,Institute for Family Planning |
And 7 more authors.
Journal of Cellular Physiology | Year: 2013
Mono (2-ethylhexyl) phthalate (MEHP), an environmental contaminant, is known to cause many serious diseases, especially in reproductive system. However, little is known about the effect of MEHP on preimplantation embryo development. In this study, we found that the development of mouse 2-cell embryo was blocked by 10-3M MEHP. A significant increase in the level of reactive oxygen species (ROS) was observed in arrested 2-cell embryo following 10-3M MEHP treatment for 24h. However, antioxidants, catalase (CAT), and superoxide dismutase (SOD), reduced intracellular ROS and protected MEHP-exposed embryos from death but failed to return the arrested embryos. Further experiments demonstrated that the level of apoptosis was not altered in live arrested 2-cell embryo and increased in dead arrested 2-cell embryo after MEHP treatment, which implied that ROS and apoptosis were not related with 2-cell block. During analysis of the indicators of embryonic genome activation (EGA) initiation (Hsc70, MuERV-L, Hsp70.1, eIF-1A, and Zscan4) and maternal-effect genes (OCT4 and SOX2), we found that MEHP treatment could significantly decline Hsc70, MuERV-L mRNA level and SOX2 protein level, and markedly enhance Hsp70.1, eIF-1A, Zscan4 mRNA level, and OCT4 protein level at 2-cell to 4-cell stage. Supplementation of CAT and SOD did not reverse the expression tendency of EGA related genes. Collectively, this study demonstrates for the first time that MEHP-induced 2-cell block is mediated by the failure of EGA onset and maternal-effect genes, not oxidative stress and apoptosis. © 2012 Wiley Periodicals, Inc.
Xia H.-F.,Institute for Family Planning |
Xia H.-F.,Peking Union Medical College |
Cao J.-L.,Institute for Family Planning |
Cao J.-L.,Peking Union Medical College |
And 3 more authors.
Reproduction | Year: 2014
MiR199awas found tobe differentiallyexpressed inrat uteri between the prereceptive and receptive phase viamicroRNA(miRNA)microarray analysis in our previous study.However, the role of miR199a in rat embryo implantation remained unknown. In the study, northern blot results showed that the expression levels of miR199a were higher on gestation days 5 and 6 (g.d.5-6) in rat uteri than on g.d.3-4 and g.d.7-8. In situ localization of miR199a in rat uteri showed that miR199awasmainly localized in the stroma or decidua. The expression of miR199a was not significantly different in the uteri of pseudopregnant rats and evidently increased in the uteri of rats subjected to activation of delayed implantation and experimentally induced decidualization. Treatmentwith 17β-estradiol or both 17β-estradiol and progesterone significantly diminished miR199a levels. Gain of function of miR199a in endometrial stromal cells isolated from rat uteri inhibited cell proliferation and promoted cell apoptosis. Loss of function of miR199a displayed opposite roles on cell proliferation and apoptosis. Further investigation uncovered a significant inverse association between the expression of miR199a and growth factor receptor-bound protein 10 (Grb10), an imprinted gene, and miR199a could bind to the 30UTR of Grb10 to inhibit Grb10 translation. In addition, in vivo analysis found that the immunostaining of GRB10 was attenuated in the stroma or decidua from g.d.4 to 6, contrary to the enhancement of miR199a. Collectively, upregulation of miR199a in rat uterus during the receptive phase is regulated by blastocyst activation and uterine decidualization. Enforced miR199a expression suppresses cell proliferation partially through targeting Grb10. © 2014 Society for Reproduction and Fertility.
Song P.-P.,Institute for Family Planning |
Song P.-P.,Peking Union Medical College |
Hu Y.,Institute for Family Planning |
Hu Y.,Peking Union Medical College |
And 10 more authors.
American Journal of Obstetrics and Gynecology | Year: 2011
Objective: The objective of the study was to investigate the expression and regulation of polycomb group (PcG) proteins in human neural tube defects (NTDs). Study Design: PcG proteins in human NTD fetuses and age-matched controls were detected by Western blot. The relation between PcG proteins and microribonucleic acids was predicted and confirmed by the bioinformatics method, real-time polymerase chain reaction (PCR), dual-luciferase activity assay, and Western blot. The trimethyl condition of histone H3 Lys27 (H3K27) was detected by immunohistochemical and immunofluorescence. Results: Embryonic ectoderm development protein (EED) was differentially detected in placenta, cerebral cortex, and spinal cord from NTDs and age-matched controls. MiR-30b can interact with 3'-untranslated region (UTR) of Eed and regulate endogenous EED expression in neural tissues. In addition, we found an inverse relationship between the miR-30b expression and the amount of trimethyl H3K27. Conclusion: Differential expression of EED exists in the nerves system in human NTDs and that is regulated by miR-30b. © 2011 Published by Mosby, Inc.
Liu S.,Peking Union Medical College |
Liu S.,Institute for Family Planning |
Tian W.,Tianjin Hospital |
Tian W.,Tianjin Medical University |
And 9 more authors.
Genetic Testing and Molecular Biomarkers | Year: 2014
Aims: Developmental dysplasia of the hip (DDH) is a common congenital or acquired skeletal disease characterized by subluxation, dislocation, or dysplasia of the hip joint. This study aimed to explore the potential impact of Dickkopf-1 (DKK1) gene polymorphisms on embryonic hip joint development and the course of DDH. Methods: One hundred ninety-two unrelated Chinese Han female DDH patients and 191 unrelated, healthy, ethnically matched female controls were recruited and genotyped for two tag single-nucleotide polymorphisms (SNPs) of DKK1 using the Sequenom method. Results: One of the two DKK1 tag SNPs, rs11001560, was not shown to be significantly statistically different in allele frequency between DDH patients and control groups (χ2=0.898, df=1, p=0.343). However, a significant difference in genotype distribution was observed (χ2=21.987, df=2, p<0.0001). For SNP rs1569198, significant differences were observed in both allele frequency and genotype distribution between the DDH group and control group (χ2=31.484, df=1, p<0.0001 and χ2=30.323, df=2, p<0.0001). The A allele frequency of rs1569198 has a significant association to increased risk of DDH development (odds ratio [OR]=3.032, 95% confidence interval [95% CI]: 2.034-4.519). Conclusion: In conclusion, the association between two tag SNPs of the DKK1 gene and DDH development reached statistical significance in our study population; the results of our genetic association analysis indicated that DKK1 may be a good candidate responsible for DDH development in the Chinese Han female population. © Copyright 2014, Mary Ann Liebert, Inc. 2014.