title: Uterine Rbpj is required for embryonic-uterine orientation and decidual remodeling via Notch pathway-independent and -dependent mechanisms.
abstract: Coordinated uterine-embryonic axis formation and decidual remodeling are hallmarks of mammalian post-implantation embryo development. Embryonic-uterine orientation is determined at initial implantation and synchronized with decidual development. However, the molecular mechanisms controlling these events remain elusive despite its discovery a long time ago. In the present study, we found that uterine-specific deletion of Rbpj, the nuclear transducer of Notch signaling, resulted in abnormal embryonic-uterine orientation and decidual patterning at post-implantation stages, leading to substantial embryo loss. We further revealed that prior to embryo attachment, Rbpj confers on-time uterine lumen shape transformation via physically interacting with uterine estrogen receptor (ERα) in a Notch pathway-independent manner, which is essential for the initial establishment of embryo orientation in alignment with uterine axis. While at post-implantation stages, Rbpj directly regulates the expression of uterine matrix metalloproteinase in a Notch pathway-dependent manner, which is required for normal post-implantation decidual remodeling. These results demonstrate that uterine Rbpj is essential for normal embryo development via instructing the initial embryonic-uterine orientation and ensuring normal decidual patterning in a stage-specific manner. Our data also substantiate the concept that normal mammalian embryonic-uterine orientation requires proper guidance from developmentally controlled uterine signaling.
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Shuang
authors: S
authors: Zhang
authors: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100101, China.
authors: Shuangbo
authors: S
authors: Kong
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Bingyan
authors: B
authors: Wang
authors: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] Reproductive Medical Center, The Third Affiliated Hospital of Guangzhou Medical College, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, Guangdong, China.
authors: Xiaohong
authors: X
authors: Cheng
authors: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100101, China.
authors: Yongjie
authors: Y
authors: Chen
authors: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100101, China.
authors: Weiwei
authors: W
authors: Wu
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Qiang
authors: Q
authors: Wang
authors: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100101, China.
authors: Junchao
authors: J
authors: Shi
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Ying
authors: Y
authors: Zhang
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Shumin
authors: S
authors: Wang
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Jinhua
authors: J
authors: Lu
authors: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors: John P
authors: JP
authors: Lydon
authors: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors: Francesco
authors: F
authors: DeMayo
authors: Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Warren S
authors: WS
authors: Pear
authors: 1] Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi 710032, China [2] State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an, Shanxi 710032, China.
authors: Hua
authors: H
authors: Han
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Haiyan
authors: H
authors: Lin
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Lei
authors: L
authors: Li
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Hongmei
authors: H
authors: Wang
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Yan-Ling
authors: YL
authors: Wang
authors: Reproductive Medical Center, The Third Affiliated Hospital of Guangzhou Medical College, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, Guangdong, China.
authors: Bing
authors: B
authors: Li
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Qi
authors: Q
authors: Chen
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Enkui
authors: E
authors: Duan
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Haibin
authors: H
authors: Wang
mesh_terms: D000818:Animals; D010064:Embryo Implantation; D004622:Embryo, Mammalian / Q000502:physiology; D047108:Embryonic Development; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D051880:Receptors, Notch / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014599:Uterus / Q000378:metabolism* / Q000473:pathology
chemical_list: D047628:Estrogen Receptor alpha; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497571:Rbpj protein, mouse; D051880:Receptors, Notch; D014157:Transcription Factors; D020782:Matrix Metalloproteinases