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En-Kui DUAN, Ph. D.

embryo implantation,epidermal development and skin stem cell regulation


Co-workers: Ying Zhang, Yujing Cao, Xiaohua Lei, Yusheng Liu, Yufang Zhang, Yongcun Qu, Jingjing Qian, Liwen Zhang

• DUAN Group website

 

  1. A precisely regulated intrauterine environment has been shown to be responsible for pregnancy establishment, and a disruption of the uterine fluid homeostasis (in volume and/or molecular contents) during this process can cause abnormal embryo implantation and pregnancy loss. During this critical time window, the communications between the embryo and uterus before and during implantation are susceptible to maternal conditions, the disturbance of which can represent an important cause of not only defective embryonic development, but also adult-onset diseases. Before and during embryo implantation, uterine fluid is the liquid medium that connects floating embryo(s) and uterus; this fluid has the potential to transfer vital information between the embryo and uterus, in addition to simply serving as a buffer medium. We are interested in the molecular/biomechanical regulations of intrauterine fluids regulation that are critical for “on site” embryo implantation, as well as uterine fluid mediated maternal epigenetic information transfer in early prengnancy.

  2. Increasing evidence indicates that metabolic disorders in offspring can affect the germ line and influence future generations through epigenetic mechanisms. DNA methylation and histone modification were affected and participated into intergenerational/transgenerational epigenetic inheritances. We also found sperm RNA can also carry environmental exposure information. Herein, we are now investigating the function of sperm RNAs and RNA modifications in epigenetic message intergenerational/transgenerational transfer.



Schematic diagrams showing the process and regulatory factors of embryo distribution along the uterine longitudinal axis (mice).



Maternal Environmental Exposure Might Epigenetically Influence the Embryo via Uterine Fluid

 

Plain english:
  Pregnancy loss is a common and painful condition for gestational women, accounting for 25-40% of total pregnancy, having become a serious social-medical issue worldwide. Both animal studies and clinical investigations have indicated that the cause of many mid-term miscarriage/abnormal pregnancy was seeded very early at the onset of embryo implantation. Normal embryo implantation requires accurate timing and locations within the uteri, abnormal intrauterine embryo distribution and timing are important cause for adverse embryo development and miscarriage. Our group use transgenic/knockout mice as model system, combining cellular, molecular and computational/biomechanical approaches to study the mechanisms how the embryos are transported to the optimal sites and how to initiate implantation process.
  Emerging evidence now supports the notion that the certain paternal traits that are acquired in response to ancestral exposures, such as toxicant contact, mental stresses and diet changes, can be inherited by the offspring. During this process, paternally acquired traits can be ‘memorized’ in the germ cell as epigenetic information or be carried to embryos through pregnant process. Our studies want to reveal the possible mechanisms by which the germ cells or maternal internal environment become acquisitives following environmental–somatic–germline interactions, and how they transmit parentally acquired phenotypes by shaping early embryonic development.

 

Selected publications:

  1. Zhang Y, Wang Q, Wang H, Duan E*. (2017) Uterine Fluid in Pregnancy: A Biological and Clinical Outlook. Trends Mol Med. 2017 Jul;23(7):604-614. (Cover story & Cell Press news &F1000 recommend)
  2. Chen Q*, Yan W*, Duan E*. Epigenetic inheritance of acquired traits through sperm RNAs and sperm RNA modifications. Nat Rev Genet. 2016 Dec;17(12):733-743.
  3. Chen Q, Yan M, Cao Z, Li X, Zhang Y, Shi J, Feng G, Peng H, Zhang X, Zhang Y, Qian J, Duan E*, Zhai Q*, Zhou Q*. Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science. 2016 Jan 22;351(6271):397-400. (Highlight paper)
  4. Shi J, Chen Q, Li X, Zheng X, Zhang Y, Qiao J, Tang F, Tao Y*, Zhou Q*, and Duan E*. Dynamic transcriptional symmetry-breaking in pre-implantation mammalian embryo development revealed by single-cell RNA-seq. Development. 2015 142, 3468-3477. (Highlight paper)
  5. Zhao Q, Liu S, Zhang H, Li N, Wang X, Cao Y, Ning L, Duan E*, and Xia G*. Spatiotemporal Expression of p63 in Mouse Epidermal Commitment. Int J Mol Sci. 2015 Dec 10;16(12):29542-53.
  6. Zhang H, Zhang S, Zhao H, Qiao J, Liu S, Deng Z, Lei X, Ning L, Cao Y, Zhao Y, and Duan E*. Ovine Hair Follicle Stem Cells Derived from Single Vibrissae Reconstitute Haired Skin. Int J Mol Sci.2015 16, 17779-17797.
  7. Zhang S, and Duan E*. Epigenetic regulations on skin wound healing: implications from current researches. Ann Transl Med. 2015 3, 227
  8. Ning L, Lei X, Cao Y, Zhang Y, Cao Z, Chen Q, andDuan E*. Effect of Short-Term Hypergravity Treatment on Mouse 2-Cell Embryo Development.Microgravity Sci. Technol. 2015 27:465–471.
  9. Liu S, Wang X, Zhao Q, Liu S, Zhang H, Shi J, Li N, Lei X, Zhao H, Deng Z, Cao Y, Ning L, Xia G, Duan E*. Senescence of human skin-derived precursors regulated by Akt-FOXO3-p27KIP1/p15 INK4b signaling. Cell Mol Life Sci. 2015 Aug;72(15):2949-60.
  10. Deng Z, Lei X, Zhang X, Zhang H, Liu S, Chen Q, Hu H, Wang X, Ning L, Cao Y, Zhao T, Zhou J, Chen T, Duan E*. mTOR signaling promotes stem cell activation via counterbalancing BMP-mediated suppression during hair regeneration. J Mol Cell Biol. 2015 Feb;7(1):62-72.
  11. Zhang Y, Chen Q, Zhang H, Wang Q, Rong L, Jin Y, Wang H, Ma T*, Qiao J*, Duan E*. Aquaporin-mediated excessive intrauterine fluid is a major contributor in hyper-estrogen induced aberrant embryo implantation. Cell Res. 2015 Jan;25(1):139-42.
  12. Zhang S, Kong S, Wang B, Cheng X, Chen Y, Wu W, Wang Q, Shi J, Zhang Y, Wang S, Lu J, Lydon JP, DeMayo F, Pear WS, Han H, Lin H, Li L, Wang H, Wang YL, Li B, Chen Q*, Duan E*, Wang H*.Uterine Rbpj is required for embryonic-uterine orientation and decidual remodeling via Notch pathway-independent and -dependent mechanisms.Cell Res.2014 Jun 27. doi: 10.1038/cr.2014.82. [Epub ahead of print](Cover story) .
  13. Zhang Y, Zhang Y, Shi J, Zhang H, Cao Z, Gao X, Ren W, Ning Y, Ning L, Cao Y, Chen Y, Ji W, Chen Z*, Chen Q*, Duan E*. Identification and characterization of an ancient class of small RNAs enriched in serum associating with active infection.J Mol Cell Biol 2014 Feb 24;6(2):172-174 (Cover story) .
  14. Wang X, Liu S, Zhao Q, Li N, Zhang H, Zhang X, LeiX, Zhao H, Deng Z, Qiao J, Cao Y, Ning L,Liu S*,Duan E* Three-dimensional hydrogel scaffolds facilitate in vitro self-renewal of human skin-derived precursors,Acta Biomaterialia, 2014 10(7):3177-3187.
  15. Chen Q, Zhang Y, Elad D, Jaffa AJ, Cao Y, Ye X*,Duan E*. Navigating the site for embryo implantation: Biomechanical and molecular regulation of intrauterine embryo distribution.Mol Aspects Med. 2013 Oct;34(5):1024-42 (Invited review) .
  16. Peng H, Shi J, Zhang Y, Zhang H, Liao S, Li W, Lei L, Han C, Ning L, Cao Y, Zhou Q, Chen Q*,Duan E*A novel class of tRNA-derived small RNAs extremely enriched in mature mouse sperm.Cell Res. 2012.22(11):1609-12. (Highlight paper) .
  17. Liu S, Liu S, Wang X, Zhou J, Cao Y, Wang F,Duan E*. The PI3K-Akt pathway inhibits senescence and promotes self-renewal of human skin-derived precursors in vitro. Aging Cell. 2011 Aug;10(4):661-74.
  18. Chen Q, Zhang Y, Peng H, Lei L, Kuang H, Zhang L, Ning L, Cao Y, Duan E*. Transient β2-Adrenoceptor activation confers pregnancy loss by disrupting embryo spacing at implantation. J Biol Chem. 2011 286(6):4349-4356.
  19. Chen Q, Peng H, Lei L, Zhang Y, Kuang H, Cao Y, Shi QX, Ma T, Duan E*. Aquaporin3 is a sperm water channel essential for postcopulatory sperm osmoadaptation and migration. Cell Res. 2011 Jun;21(6):922-33.