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En-Kui DUAN, Ph. D.

embryo implantation,small RNA mediated epigenetic inheritance


Co-workers: Ying Zhang, Yujing Cao, Xiaohua Lei, Chiyuan Ma, Yongcun Qu, Jingjing Qian, Liwen Zhang

· DUAN Group website

 

  1. 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.

  2. 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 pregnancy.

  3. We explored mouse preimplantation embryonic development during the spaceflight of China's SJ-10 recoverable satellite. After sending the 2-cell mouse embryo into space, we got the embryonic develop video, and found mouse early embryo could develop to blastocysts in the space. We are detecting the potential effects of radiation and microgravity on early embryo development.



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 in last 5 years:

  1. Qian J, Chen Q, Sean M. Ward, Duan E*, Zhang Y*. Impacts of caffeine during pregnancy. Trends in Endocrinology and Metabolism. 2020 Mar;31(3):218-227.
  2. Zhang Y, Qian J, Oren Z, Mustafa B, Ariel J.J, Dan G, Duan E, David E. Analysis of in vivo uterine peristalsis in the non-pregnant female mouse. Interface Focus. 2019 Aug 6;9(4):20180082.
  3. Zhang Y, Chen Q. The expanding repertoire of hereditary information carriers. Development. 2019 Mar 15;146(6). pii: dev170902
  4. Zhang Y, Zhang X, Shi J, Tuorto F, Li X, Liu Y, Liebers R, Zhang L, Qu Y, Qian J, Pahima M, Liu Y, Yan M, Cao z, Cao Y, Peng H, Liu S, Wang Y, Zheng H, Woolsey R, Zhai Q, Li L, Zhou T, Yan W, Lyko F, Zhang Y*, Zhou Q*, Duan E*, Chen Q*. Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs. Nature Cell Biology 2018; 20:535-540.
  5. Zhang Y, Duan E. LncRNAs and paraspeckles predict cell fate in early mouse embryo. Biology of Reproduction. 2019 May 1;100(5):1129-1131
  6. Qian J, Zhang Y, Qu Y, Zhang L, Shi J, Zhang X, Liu S, Kim BH, Hwang SJ, Zhou T, Chen Q, Ward SM, Duan E*, Zhang Y*. Caffeine consumption during early pregnancy impairs oviductal embryo transport, embryonic development and uterine receptivity in mice. Biology of Reproduction 2018; Dec 1;99(6):1266-1275
  7. Zhang Y, Wang Q, Wang H, Duan E. Uterine Fluid in Pregnancy: A Biological and Clinical Outlook. Trends in Molecular Medicine. 2017 Jul;23(7):604-614.
  8. 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.
  9. 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)
  10. 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)
  11. 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.
  12. 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.
  13. Zhang S, and Duan E*. Epigenetic regulations on skin wound healing: implications from current researches. Ann Transl Med. 2015 3, 227
  14. 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.
  15. 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.
  16. 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.
  17. Zhang Y, Chen Q, Zhang H, Wang Q, Rong L, Jin Y, Wang H, Ma T*, Qiao J*Duan E*. Aquaporin-mediated excessive intrauterine ?uid is a major contributor in hyper-estrogen induced aberrant embryo implantation. Cell Res. 2015 Jan;25(1):139-42.