Tridimensional visualization reveals direct communication between the embryo and glands critical for implantation

• Published in: Nature communications Vol. 9; no. 1; pp. 603 - 13
• Main Authors: Yuan, Jia, Deng, Wenbo, Cha, Jeeyeon, Sun, Xiaofei, Borg, Jean-Paul, Dey, Sudhansu. K.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.02.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 14/1; 14/19; 14/69; 631/136/2086; 631/136/3194; 631/1647/245/2221; 631/443/494/2732/1577; Animals; Beads; Blastocyst - cytology; Blastocyst - drug effects; Blastocyst - physiology; Blastocysts; Casing (process); Cell Communication - drug effects; Cell Communication - genetics; Cell Communication - physiology; Cell Polarity - genetics; Cell Polarity - physiology; Clonal deletion; Crypts; Elongation; Embryo Implantation - genetics; Embryo Implantation - physiology; Embryos; Epithelial cells; Female; Gene deletion; Gene Expression Regulation, Developmental; Glands; Heparin-binding EGF-like Growth Factor - genetics; Heparin-binding EGF-like Growth Factor - metabolism; Heparin-binding EGF-like Growth Factor - pharmacology; Humanities and Social Sciences; Imaging, Three-Dimensional - methods; Implantation; Life Sciences; Male; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Microscopy, Confocal; multidisciplinary; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Polarity; Pregnancy; Pseudopregnancy; Science; Science (multidisciplinary); Uterus; Uterus - cytology; Uterus - metabolism; Uterus - physiology; Visualization; Embryogenesis; Intrauterine growth; Infertility; 3-D reconstruction
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-03092-4

Embryo implantation is central to pregnancy success. Our previous understanding is limited by studying this phenomenon primarily in two dimensions. Here we employ 3D visualization, revealing that epithelial evaginations that form implantation chambers (crypts) consistently arise with preexisting glands, suggesting direct access of glands to embryos within the chamber. While the lobular domains of the glands become more developed, the ductal regions continue to elongate and progressively stretch following implantation. Using diapausing mice and mice with deletion of the planar cell polarity gene Vangl2 in uterine epithelial cells, we show that dynamic changes in gland topography depend on implantation-competent blastocysts and planar cell polarity. By transferring blastocyst-size beads preloaded with HB-EGF in pseudopregnant mice, we found that HB-EGF is a trigger for the communication between embryos and glands. Glands directly connecting the crypt encasing the embryo during implantation are therefore fundamental to pregnancy success. Embryo implantation initiates the interaction of the blastocyst with the uterus and occurs within a specialised crypt formed by uterine epithelial cells. Here, using 3D imaging techniques of wild type and mutant uteri, the authors show that crypt formation occurs with preexisting glands of the uterus, opening communication between glands and the implanting embryo.