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段恩奎 研究员

胚胎植入,小RNA介导获得性性状传递

欢迎您加入胚胎生物学研究组!
- 副研究员:张莹
- 工作人员:曹宇静,雷晓华,马驰原
- 研究生:曲永存,钱静静,张力文

· 查看段恩奎实验室网页

 

  1. 父代的获得性性状能通过精子传递到受精卵中,影响子代健康。除了精子DNA甲基化和组蛋白修饰能携带父代的表观遗传信息外,精子RNA也发挥了关键作用。我们将研究精子RNA及其修饰在父代获得性性状代际/跨代传递中的作用及机制。

  2. 胚胎从输卵管进入子宫后需要在子宫肌层收缩蠕动,宫腔液体的运载下输送到合适的位置,同时在宫腔液体环境中与母体子宫进行相互对话进而在子宫内膜定植。该过程涉及宫腔液体体积和分子的精确调控,是胚胎发育和植入的关键步骤。如果植入位置异常将会导致流产或胎盘前置等妊娠综合症,同时宫腔液体环境失衡将会导致胚胎发育不正常。我们将研究生理、病理情况下宫腔液体调控的分子机制、其对胚胎在子宫内定位/定向的调控,以及对早期胚胎发育的影响。

  3. 我们利用实践十返回式卫星将小鼠2细胞胚胎送上太空,捕捉到2细胞胚胎发育到囊胚的实时动画,证实哺乳动物早期胚胎能在太空发育。进一步我们继续研究太空辐射和微重力对胚胎发育的影响。



示意图展示宫腔液体介导母体妊娠环境暴露的表观遗传信息传递到胚胎,影响胎儿和胎盘发育,引起成年疾病过程

 

 

研究内容和目标:
  成功妊娠并产生健康的后代是人类繁衍的基础,也是生殖生物学家长期以来面临的挑战。据统计,妊娠失败在全球育龄妇女中的比例高达25-40%,已成为当今一个全球性的医学-社会问题。近年来基础和临床医学的研究发现:多数妊娠失败病人的病因都起源于胚胎植入期的异常。正常的胚胎植入需要胚胎发生在子宫内的正确位置和准确的时间,植入位置/方向及时间的异常均可严重影响胚胎的后续发育,是导致流产的重要因素。我们的研究拟通过转基因动物模型,分子/细胞生物学以及电脑模拟等手段阐明植入前后调控胚胎宫内定位和植入的分子/生理/生物力学机制。
  最近的研究也显示亲代的环境暴露能通过妊娠过程传递给子代,影响子代健康。在这个过程中生殖细胞及母体环境表观遗传信息的改变被认为传递到胚胎中,导致成年相关疾病的产生。我们的研究拟揭示表观遗传信息的传递通路,即父母亲环境暴露如何引起表观遗传信息的改变并传递到胚胎中,胚胎发生什么样的改变,如何影响成年子代健康。

 

近5年代表性文章:

  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.