Three-dimensional understanding of the morphological complexity of the human uterine endometrium
Manako Yamaguchi,
Kosuke Yoshihara,
Kazuaki Suda,
Hirofumi Nakaoka,
Nozomi Yachida,
Haruka Ueda,
Kentaro Sugino,
Yutaro Mori,
Kaoru Yamawaki,
Ryo Tamura,
Tatsuya Ishiguro,
Teiichi Motoyama,
Yu Watanabe,
Shujiro Okuda,
Kazuki Tainaka,
Takayuki Enomoto
Affiliations
Manako Yamaguchi
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Kosuke Yoshihara
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Corresponding author
Kazuaki Suda
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Hirofumi Nakaoka
Human Genetics Laboratory, National Institute of Genetics, Mishima 411-8540, Japan; Department of Cancer Genome Research, Sasaki Institute, Sasaki Foundation, Chiyoda-ku 101-0062, Japan
Nozomi Yachida
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Haruka Ueda
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Kentaro Sugino
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Yutaro Mori
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Kaoru Yamawaki
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Ryo Tamura
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Tatsuya Ishiguro
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Teiichi Motoyama
Department of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Yu Watanabe
Division of Bioinformatics, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Shujiro Okuda
Division of Bioinformatics, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Kazuki Tainaka
Department of System Pathology for Neurological Disorders, Brain Research Institute, Niigata University, Niigata 951-8585, Japan; Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, Suita 565-5241, Japan; Corresponding author
Takayuki Enomoto
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Corresponding author
Summary: The fundamental morphology of the endometrial glands is not sufficiently understood by 2D observation because these glands have complicated winding and branching patterns. To construct a large picture of the endometrial gland structure, we performed tissue-clearing-based 3D imaging of human uterine endometrial tissue. Our 3D immunohistochemistry and layer analyses revealed that the endometrial glands form a plexus network in the stratum basalis and expand horizontally along the muscular layer, similar to the rhizome of grass. We then extended our method to assess the 3D morphology of tissue affected by adenomyosis, a representative “endometrium-related disease,” and observed its 3D morphological features, including the direct invasion of endometrial glands into the myometrium and an ant colony-like network of ectopic endometrial glands within the myometrium. Thus, further understanding of the morphology of the human endometrium based on 3D analysis will lead to the identification of the pathogenesis of endometrium-related diseases.