File:Implantation cartoon 01.jpg

This is a hybrid cartoon, based on mouse and human studies, portraying compartment- and cell-type–specific expression of molecules and their potential functions necessary for uterine receptivity, implantation and decidualization. Interplay of ovarian P4- and/or E2-dependent and P4- and/or E2-independent factors in the pregnant uterus in specific compartments contributes to the success of implantation in a juxtacrine/paracrine/autocrine manner. During attachment, interactions between the blastocyst and luminal epithelium (LE) involve ErbB1/4 (blue) and both transmembrane (TM) and soluble (Sol) forms of HB-EGF, as well as L-selectin ligands (sLE) expressed by the luminal epithelium to L-selectin receptors on the blastocyst. The other key signaling pathways for uterine receptivity and implantation are also shown. AA, arachidonic acid; BMP2, bone morphogenetic protein 2; cPLA2α, cytosolic phospholipase A2α; COUP-TFII, chicken ovalbumin upstream promoter transcription factor-2; Cox2, cyclooxygenase-2; E, estrogens; EC, epithelial cell (luminal and glandular epithelia); ENaC, epithelium sodium channel; ER, estrogen receptor; ErbB1/4; epidermal growth factor receptor 1/4; ERK, extracellular signal–regulated kinase; FGF, fibroblast growth factor; GE, glandular epithelium; gp130, glycoprotein 130; Hand2, heart- and neural crest derivatives-expressed protein 2; HB-EGF, heparin-binding epidermal growth factor-like growth factor; Hoxa10/11, homeobox A10/11; ICM, inner cell mass; IHH, Indian hedgehog; KLF5, Kruppel-like factor 5; LIF, leukemia inhibitory factor; LIFR, LIF receptor; LPA3, lysophosphatidic acid receptor 3; MSX1, Muscle segment homeobox 1; P4, progesterone; PG, prostaglandin; PPAR-δ; peroxisome proliferators–activating receptor δ; PR, progesterone receptor; Ptc, Patched; RXR, retinoid X receptor; SC, stromal cell; SGK1, serum- and glucocorticoid-inducible kinase 1; Smo, Smoothened; STAT3, signal transducer and activator of transcription 3; Tr, trophectoderm; Wnt4/5a, Wingless-Type MMTV integration site family members 4/5a. Compartment colors: blue, stroma; pink, luminal epithelium; orange, glandular epithelium; purple, epithelium at the attachment site.

Reference

<pubmed>PMID 23223073</pubmed>| Nat Med

Copyright

Reprinted by permission from Macmillan Publishers Ltd: Nature Medicine (Mechanisms of implantation: strategies for successful pregnancy. Cha J, Sun X, Dey SK. Nat Med. 2012 Dec;18(12):1754-67. doi: 10.1038/nm.3012. Review. PMID 23223073), copyright (2012)

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