Time filter

Source Type

Liu X.-M.,Zhejiang University | Ding G.-L.,Zhejiang University | Jiang Y.,Zhejiang University | Pan H.-J.,Zhejiang University | And 7 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Background: Low expression levels of S100A11 proteins were demonstrated in the placental villous tissue of patients with early pregnancy loss, and S100A11 is a Ca2+-binding protein that interprets the calcium fluctuations and elicits various cellular responses. Objectives: The objective of the study was to determine S100A11 expression in human endometrium and its roles in endometrial receptivity and embryo implantation. Methods: S100A11 expression in human endometrium was analyzed using quantitative RT-PCR, Western blot, and immunohistochemical techniques. The effects of S100A11 on embryo implantation were examined using in vivo mouse model, and JAr (a human choriocarcinoma cell line) spheroid attachment assays. The effects of endometrial S100A11 on factors related to endometrial receptivity and immune responses were examined. Using a fluorescence method, we examined the changes in cytosolic Ca2+ and Ca2+ release from intracellular stores in epidermal growth factor (EGF)-treated endometrial cells transfected with or without S100A11 small interfering RNA. Results: S100A11 was expressed in human endometrium. S100A11 protein levels were significantly lower in endometrium of women with failed pregnancy than that in women with successful pregnancy outcomes. The knockdown of endometrial S100A11 not only reduced embryo implantation rate in mouse but also had adverse effects on the expression of factors related to endometrial receptivity and immune responses in human endometrial cells. Immunofluorescence analysis showed that S100A11 proteins were mainly localized in endoplasmic reticulum. The EGF up-regulated endometrial S100A11 expression and promoted the Ca2+ uptake and release from Ca2+ stores, which was inhibited by the knockdown of S100A11. Conclusions: Endometrial S100A11 is a crucial intermediator in EGF-stimulated embryo adhesion, endometrium receptivity, and immunotolerance via affecting Ca2+ uptake and release from intracellular Ca2+ stores. Down-regulation of S100A11 may cause reproductive failure. Copyright © 2012 by The Endocrine Society.

Guo J.,Zhejiang University | Tian T.,Zhejiang University | Lu D.,Zhejiang University | Xia G.,Zhejiang University of Science and Technology | And 4 more authors.
Journal of Obstetrics and Gynaecology Research | Year: 2012

Aim: To clarify the alterations of myostatin, a member of the transforming growth factor-b superfamily, and follistatin-like 3 (FSTL3), a binding protein for myostatin, in pre-eclamptic women. Methods: Samples of blood and placenta were collected from 40 pre-eclamptic women and 40 controls. The serum level and placental expression of FSTL3 and myostatin were determined with enzyme-linked immunosorbent assay, real-time polymerized chain reaction and western blotting. Results: The serum levels of myostatin and FSTL3 were significantly higher in pre-eclamptic women than in the controls (P < 0.001 for both). Placental expression of myostatin and FSTL3 were also significantly increased in the pre-eclamptic placenta compared with that of the controls (P < 0.001 for both); however, there were no significant differences in myostatin or FSTL3 in either the maternal serum or the placenta in women with mild or severe pre-eclampsia (P > 0.05 for both). Conclusion: The serum levels and placental expression of myostatin and FSTL3 are elevated in pre-eclampsia, suggesting the role of myostatin and its binding protein in pre-eclampsia. © 2012 The Authors.

Ding G.-L.,Zhejiang University | Wang F.-F.,Zhejiang University | Shu J.,Zhejiang University | Tian S.,Zhejiang University | And 10 more authors.
Diabetes | Year: 2012

Gestational diabetes mellitus (GDM) has been shown to be associated with high risk of diabetes in offspring. However, the mechanisms involved and the possibilities of transgenerational transmission are still unclear. We intercrossed male and female adult control and first-generation offspring of GDM (F1-GDM) mice to obtain the second-generation (F2) offspring in four groups: C♂-C♀, C♂-GDM♀, GDM♂-C♀, and GDM♂-GDM♀. We found that birth weight significantly increased in F2 offspring through the paternal line with impaired glucose tolerance (IGT). Regardless of birth from F1-GDM with or without IGT, high risk of IGT appeared as early as 3 weeks in F2 offspring and progressed through both parental lineages, especial the paternal line. IGT in male offspring was more obvious than that in females, with parental characteristics and sex-specific transmission. In both F1 and F2 offspring of GDM, the expression of imprinted genes Igf2 and H19 was downregulated in pancreatic islets, caused by abnormal methylation status of the differentially methylated region, which may be one of the mechanisms for impaired islet ultrastructure and function. Furthermore, altered Igf2 and H19 gene expression was found in sperm of adult F1-GDM, regardless of the presence of IGT, indicating that changes of epigenetics in germ cells contributed to transgenerational transmission. © 2012 by the American Diabetes Association.

Wang C.,Key Laboratory of Reproductive Genetics | Wang C.,Zhejiang University | Zhao L.,Key Laboratory of Reproductive Genetics | Zhao L.,Zhejiang University | And 2 more authors.
International Journal of Biological Sciences | Year: 2015

Telomere dysfunction is closely associated with human diseases such as cancer and ageing. Inappropriate changes in telomere length and/or structure result in telomere dysfunction. Telomeres have been considered to be transcriptionally silent, but it was recently demonstrated that mammalian telomeres are transcribed into telomeric repeat-containing RNA (TERRA). TERRA, a long non-coding RNA, participates in the regulation of telomere length, telomerase activity and heterochromatinization. The correct regulation of telomere length may be crucial to telomeric homeostasis and functions. Here, we summarize recent advances in our understanding of the crucial role of TERRA in the maintenance of telomere length, with focus on the variety of mechanisms by which TERRA is involved in the regulation of telomere length. This review aims to enable further understanding of how TERRA-targeted drugs can target telomere-related diseases. © 2015 Ivyspring International Publisher.

Lu Y.-C.,Zhejiang University | Ding G.-L.,Zhejiang University | Yang J.,Zhejiang University | Zhang Y.-L.,Zhejiang University | And 9 more authors.
Human Reproduction | Year: 2012

Background The present study was designed to investigate the expression of small-conductance calcium-activated K+ channels 3 (SK3) in preimplantation embryos and to explore their role in the underlying mechanism of blastocyst hatching. Methods Human preimplantation embryos were donated by patients who achieved successful pregnancy with in vitro fertilization. Mouse preimplantation embryos in different stages were collected and cultured with or without siRNA cell injection. The expression of SK3 was examined by RTPCR, quantitative real-time PCR, western blot and immunofluorescence. Functional expression of SK3 was investigated using the patch-clamp technique. [Ca 2]i was measured by fluorescent imaging. Embryos were cultured in vitro to investigate the effect of SK3 knockdown or apamin, an SK3 inhibitor, on blastocyst hatching and F-actin formation. Results In human blastocysts, the level of SK3 expression was significantly lower in blastocysts that failed to hatch than in blastocysts that hatched successfully. In mouse embryos, SK3 mRNA and protein were not found in zygotes, but were detected from the 2-cell stage onward, with the highest levels observed in blastocysts. SK3 was predominately located in the trophectoderm cell membrane of expanded blastocysts. SK3 knockdown in trophectoderm cells not only suppressed the SK3 current, but also reduced [Ca2]i elevation and membrane potential hyperpolarization induced by thapsigargin. Although the formation of expanded blastocysts was not affected, blastocyst hatching and F-actin formation were significantly inhibited after SK3 knockdown in trophectoderm cells. Conclusions SK3-mediated [Ca 2]i elevation and membrane potential hyperpolarization in trophectoderm cells are important for blastocyst hatching, and defects in SK3 expression may contribute to infertility. © 2012 The Autho.

Discover hidden collaborations