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Cited by 112Reproductive System and PregnancyReproductive Biology and FertilityPregnancy and preeclampsia studies

Role of uterine stromal-epithelial crosstalk in embryo implantation

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Hantak, Alison M., Bagchi, Indrani C., Bagchi, Milan K.·2014·The International Journal of Developmental Biology
DOI 10.1387/ijdb.130348mbPMC PMC4768910
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Abstract

Embryo implantation is a crucial step for successful pregnancy. Prior to implantation, the luminal epithelium undergoes steroid hormone-induced structural and functional changes that render it competent for embryo attachment. Subsequent invasion of the embryo into the maternal tissue triggers differentiation of the underlying stromal cells to form the decidua, a transient tissue which supports the developing embryo. Many molecular cues of both stromal and epithelial origin have been identified that are critical mediators of this process. An important aspect of uterine biology is the elaborate crosstalk that occurs between these tissue compartments during early pregnancy through expression of paracrine factors regulated by the steroid hormones estrogen and progesterone. Aberrant expression of these factors often leads to implantation failure and infertility. Genetically-engineered mouse models have been instrumental in elucidating what these paracrine factors are, what drives their expression, and what their effects are on neighboring cells. This review provides an overview of several well-characterized signaling pathways that span both epithelial and stromal compartments and their function during implantation in the mouse.

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  • In the mouse uterus, dexamethasone blocks estrogen-mediated induction of Igf-1, a key growth factor stimulating epithelial cell proliferation.

    “In the mouse uterus, dexamethasone blocks estrogen-mediated induction of insulin-like growth factor-I (Igf-1), a key growth factor stimulating epithelial cell proliferation [55,56,57].”

    From Stress and the HPA Axis: Balancing Homeostasis and Fertility. (2017) · cites this paper as [57]

    The ‘Stromal Factors Regulating Epithelial Function’ section says estrogen induces uterine Igf1 and describes IGF1’s role in estrogen-induced epithelial proliferation. It does not say that dexamethasone blocks Igf1 induction; searches for dexamethasone and glucocorticoid inhibition found no supporting passage. Page numbers were not available in our copy. (LLM, conf=0.88)

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Research works printed but not linked: 59

  1. ADESANYA OO ZHOU J SAMATHANAM C POWELL-BRAXTON L BONDY CA Insulin-like growth factor 1 is required for G2 progression in the estradiol-induced mitotic cycle Proc Natl Acad Sci U S A 1999 96 3287 3291 10077676 PMC15934
  2. BHATT H BRUNET LJ STEWART CL Uterine expression of leukemia inhibitory factor coincides with the onset of blastocyst implantation Proc Natl Acad Sci U S A 1991 88 11408 11412 1722331 PMC53144
  3. BUCHANAN DL SETIAWAN T LUBAHN DB TAYLOR JA KURITA T CUNHA GR COOKE PS Tissue compartment-specific estrogen receptor-alpha participation in the mouse uterine epithelial secretory response Endocrinology 1999 140 484 491 9886861
  4. CATALANO RD JOHNSON MH CAMPBELL EA CHARNOCK-JONES DS SMITH SK SHARKEY AM Inhibition of Stat3 activation in the endometrium prevents implantation: a nonsteroidal approach to contraception Proc Natl Acad Sci U S A 2005 102 8585 8590 15937114 PMC1150834
  5. CHA J SUN X DEY SK Mechanisms of implantation: strategies for successful pregnancy Nat Med 2012 18 1754 1767 23223073 PMC6322836
  6. CHEN JR CHENG JG SHATZER T SEWELL L HERNANDEZ L STEWART CL Leukemia inhibitory factor can substitute for nidatory estrogen and is essential to inducing a receptive uterus for implantation but is not essential for subsequent embryogenesis Endocrinology 2000 141 4365 4372 11108244
  7. CHENG JG CHEN JR HERNANDEZ L ALVORD WG STEWART CL Dual control of LIF expression and LIF receptor function regulate Stat3 activation at the onset of uterine receptivity and embryo implantation Proc Natl Acad Sci U S A 2001 98 8680 8685 11438698 PMC37495
  8. COOKE PS BUCHANAN DL YOUNG P SETIAWAN T BRODY J KORACH KS TAYLOR J LUBAHN DB CUNHA GR Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium Proc Natl Acad Sci USA 1997 94 6535 6540 9177253 PMC21085
  9. DAIKOKU T CHA J SUN X TRANGUCH S XIE H FUJITA T HIROTA Y LYDON J DEMAYO F MAXSON R DEY SK Conditional deletion of Msx homeobox genes in the uterus inhibits blastocyst implantation by altering uterine receptivity Dev Cell 2011 21 1014 1025 22100262 PMC3241866
  10. DAIKOKU T SONG H GUO Y RIESEWIJK A MOSSELMAN S DAS SK DEY SK Uterine Msx-1 and Wnt4 signaling becomes aberrant in mice with the loss of leukemia inhibitory factor or Hoxa-10: evidence for a novel cytokine-homeobox-Wnt signaling in implantation Mol Endocrinol 2004 18 1238 1250 14976223
  11. ESWARAKUMAR VP LAX I SCHLESSINGER J Cellular signaling by fibroblast growth factor receptors Cytokine Growth Factor Rev 2005 16 139 149 15863030
  12. FIRULLI BA HADZIC DB MCDAID JR FIRULLI AB The basic helix-loop-helix transcription factors dHAND and eHAND exhibit dimerization characteristics that suggest complex regulation of function J Biol Chem 2000 275 33567 33573 10924525 PMC2561327
  13. FRANCO HL LEE KY BROADDUS RR WHITE LD LANSKE B LYDON JP JEONG JW DEMAYO FJ Ablation of Indian hedgehog in the murine uterus results in decreased cell cycle progression, aberrant epidermal growth factor signaling, and increased estrogen signaling Biol Reprod 2010 82 783 790 20056671 PMC2842491
  14. FRANCO HL RUBEL CA LARGE MJ WETENDORF M FERNANDEZ-VALDIVIA R JEONG JW SPENCER TE BEHRINGER RR LYDON JP DEMAYO FJ Epithelial progesterone receptor exhibits pleiotropic roles in uterine development and function FASEB J 2012 26 1218 1227 22155565 PMC3289500
  15. HEWITT SC KORACH KS Oestrogen receptor knockout mice: roles for oestrogen receptors alpha and beta in reproductive tissues Reproduction 2003 125 143 149 12578528
  16. HEWITT SC LI L GRIMM SA CHEN Y LIU L LI Y BUSHEL PR FARGO D KORACH KS Research resource: whole-genome estrogen receptor α binding in mouse uterine tissue revealed by ChIP-seq Mol Endocrinol 2012 26 887 898 22446102 PMC3355558
  17. HEWITT SC LI Y LI L KORACH KS Estrogen-mediated regulation of Igf1 transcription and uterine growth involves direct binding of estrogen receptor alpha to estrogen-responsive elements J Biol Chem 2010 285 2676 2685 19920132 PMC2807324
  18. HOLLENBERG SM STERNGLANZ R CHENG PF WEINTRAUB H Identification of a new family of tissue-specific basic helix-loop-helix proteins with a two-hybrid system Mol Cell Biol 1995 15 3813 3822 7791788 PMC230620
  19. HUYEN DV BANY BM Evidence for a conserved function of heart and neural crest derivatives expressed transcript 2 in mouse and human decidualization Reproduction 2011 142 353 368 21527398 PMC3141103
  20. KAPUR S TAMADA H DEY SK ANDREWS GK Expression of insulin-like growth factor-I (IGF-I) and its receptor in the peri-implantation mouse uterus, and cell-specific regulation of IGF-I gene expression by estradiol and progesterone Biol Reprod 1992 46 208 219 1311209
  21. KREGE JH HODGIN JB COUSE JF ENMARK E WARNER M MAHLER JF SAR M KORACH KS GUSTAFSSON JA SMITHIES O Generation and reproductive phenotypes of mice lacking estrogen receptor beta Proc Natl Acad Sci U S A 1998 95 15677 15682 9861029 PMC28103
  22. KURIHARA I LEE DK PETIT FG JEONG J LEE K LYDON JP DEMAYO FJ TSAI MJ TSAI SY COUP-TFII mediates progesterone regulation of uterine implantation by controlling ER activity PLoS Genet 2007 3 e102 17590085 PMC1892047
  23. KURITA T LEE KJ COOKE PS TAYLOR JA LUBAHN DB CUNHA GR Paracrine regulation of epithelial progesterone receptor by estradiol in the mouse female reproductive tract Biol Reprod 2000 62 821 830 10727249
  24. KURITA T YOUNG P BRODY JR LYDON JP O’MALLEY BW CUNHA GR Stromal progesterone receptors mediate the inhibitory effects of progesterone on estrogen-induced uterine epithelial cell deoxyribonucleic acid synthesis Endocrinology 1998 139 4708 4713 9794483
  25. LEE DK KURIHARA I JEONG JW LYDON JP DEMAYO FJ TSAI MJ TSAI SY Suppression of ERalpha activity by COUP-TFII is essential for successful implantation and decidualization Mol Endocrinol 2010 24 930 940 20219888 PMC2870934
  26. LEE JH KIM TH OH SJ YOO JY AKIRA S KU BJ LYDON JP JEONG JW Signal transducer and activator of transcription-3 (Stat3) plays a critical role in implantation via progesterone receptor in uterus FASEB J 2013 27 2553 2563 23531596 PMC3688751
  27. LEE K JEONG J KWAK I YU CT LANSKE B SOEGIARTO DW TOFTGARD R TSAI MJ TSAI S LYDON JP DEMAYO FJ Indian hedgehog is a major mediator of progesterone signaling in the mouse uterus Nat Genet 2006 38 1204 1209 16951680
  28. LEE KY JEONG JW WANG J MA L MARTIN JF TSAI SY LYDON JP DEMAYO FJ Bmp2 is critical for the murine uterine decidual response Mol Cell Biol 2007 27 5468 5478 17515606 PMC1952078
  29. LI Q KANNAN A DEMAYO FJ LYDON JP COOKE PS YAMAGISHI H SRIVASTAVA D BAGCHI MK BAGCHI IC The antiproliferative action of progesterone in uterine epithelium is mediated by Hand2 Science 2011 331 912 916 21330545 PMC3320855
  30. LI Q KANNAN A WANG W DEMAYO FJ TAYLOR RN BAGCHI MK BAGCHI IC Bone morphogenetic protein 2 functions via a conserved signaling pathway involving Wnt4 to regulate uterine decidualization in the mouse and the human J Biol Chem 2007 282 31725 31732 17711857
  31. LI W NOTANI D MA Q TANASA B NUNEZ E CHEN AY MERKURJEV D ZHANG J OHGI K SONG X OH S KIM HS GLASS CK ROSENFELD MG Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation Nature 2013 498 516 520 23728302 PMC3718886
  32. LYDON JP DEMAYO FJ FUNK CR MANI SK HUGHES AR MONTGOMERY CA JR SHYAMALA G CONNEELY OM O’MALLEY BW Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities Genes Dev 1995 9 2266 2278 7557380
  33. MATSUMOTO H ZHAO X DAS SK HOGAN BL DEY SK Indian hedgehog as a progesterone-responsive factor mediating epithelial-mesenchymal interactions in the mouse uterus Dev Biol 2002 245 280 290 11977981
  34. MCMAHON AP More surprises in the Hedgehog signaling pathway Cell 2000 100 185 188 10660040
  35. NALLASAMY S LI Q BAGCHI MK BAGCHI IC Msx homeobox genes critically regulate embryo implantation by controlling paracrine signaling between uterine stroma and epithelium PLoS Genet 2012 8 e1002500 22383889 PMC3285581
  36. NIKAS G PSYCHOYOS A Uterine pinopodes in peri-implantation human endometrium. Clinical relevance Ann N Y Acad Sci 1997 816 129 142 9238262
  37. PAN YF WANSA KD LIU MH ZHAO B HONG SZ TAN PY LIM KS BOURQUE G LIU ET CHEUNG E Regulation of estrogen receptor-mediated long range transcription via evolutionarily conserved distal response elements J Biol Chem 2008 283 32977 32988 18728018
  38. PARIA BC MA W TAN J RAJA S DAS SK DEY SK HOGAN BL Cellular and molecular responses of the uterus to embryo implantation can be elicited by locally applied growth factors Proc Natl Acad Sci U S A 2001 98 1047 1052 11158592 PMC14706
  39. PAWAR S STAROSVETSKY E ORVIS GD BEHRINGER RR BAGCHI IC BAGCHI MK STAT3 regulates uterine epithelial remodeling and epithelial-stromal crosstalk during implantation Mol Endocrinol 2013 27 1996 2012 24100212 PMC3857199
  40. RAMATHAL CY BAGCHI IC TAYLOR RN BAGCHI MK Endometrial decidualization: of mice and men Semin Reprod Med 2010 28 17 26 20104425 PMC3095443
  41. RICHARDS RG WALKER MP SEBASTIAN J DIAUGUSTINE RP Insulin-like growth factor-1 (IGF-1) receptor-insulin receptor substrate complexes in the uterus. Altered signaling response to estradiol in the IGF-1(m/m) mouse J Biol Chem 1998 273 11962 11969 9565625
  42. RUBEL CA LANZ RB KOMMAGANI R FRANCO HL LYDON JP DEMAYO FJ Research resource: Genome-wide profiling of progesterone receptor binding in the mouse uterus Mol Endocrinol 2012 26 1428 1442 22638070 PMC3404303
  43. SIMON L SPIEWAK KA EKMAN GC KIM J LYDON JP BAGCHI MK BAGCHI IC DEMAYO FJ COOKE PS Stromal progesterone receptors mediate induction of Indian Hedgehog (IHH) in uterine epithelium and its downstream targets in uterine stroma Endocrinology 2009 150 3871 3876 19372202 PMC2717869
  44. SINGH H APLIN JD Adhesion molecules in endometrial epithelium: tissue integrity and embryo implantation J Anat 2009 215 3 13 19453302 PMC2714633
  45. SMITH AG HEATH JK DONALDSON DD WONG GG MOREAU J STAHL M ROGERS D Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides Nature 1988 336 688 690 3143917
  46. SONG H LIM H DAS SK PARIA BC DEY SK Dysregulation of EGF family of growth factors and COX-2 in the uterus during the preattachment and attachment reactions of the blastocyst with the luminal epithelium correlates with implantation failure in LIF-deficient mice Mol Endocrinol 2000 14 1147 1161 10935540
  47. STEWART CL KASPAR P BRUNET LJ BHATT H GADI I KÖNTGEN F ABBONDANZO SJ Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor Nature 1992 359 76 79 1522892
  48. SUN X BARTOS A WHITSETT JA DEY SK Uterine deletion of Gp130 or Stat3 shows implantation failure with increased estrogenic responses Mol Endocrinol 2013 27 1492 1501 23885093 PMC3753427
  49. SURVEYOR GA GENDLER SJ PEMBERTON L DAS SK CHAKRABORTY I JULIAN J PIMENTAL RA WEGNER CC DEY SK CARSON DD Expression and steroid hormonal control of Muc-1 in the mouse uterus Endocrinology 1995 136 3639 3647 7628404
  50. TAKAMOTO N ZHAO B TSAI SY DEMAYO FJ Identification of Indian hedgehog as a progesterone-responsive gene in the murine uterus Mol Endocrinol 2002 16 2338 2348 12351698
  51. THIE M HARRACH-RUPRECHT B SAUER H FUCHS P ALBERS A DENKER HW Cell adhesion to the apical pole of epithelium: a function of cell polarity Eur J Cell Biol 1995 66 180 191 7774604
  52. TSAI SJ WU MH CHEN HM CHUANG PC WING LY Fibroblast growth factor-9 is an endometrial stromal growth factor Endocrinology 2002 143 2715 2721 12072406
  53. WAKITANI S HONDO E PHICHITRASLIP T STEWART CL KISO Y Upregulation of Indian hedgehog gene in the uterine epithelium by leukemia inhibitory factor during mouse implantation J Reprod Dev 2008 54 113 116 18239353
  54. WALKER MP DIAUGUSTINE RP ZERINGUE E BUNGER MK SCHMITT M ARCHER TK RICHARDS RG An IGF1/insulin receptor substrate-1 pathway stimulates a mitotic kinase (cdk1) in the uterine epithelium during the proliferative response to estradiol J Endocrinol 2010 207 225 235 20798132 PMC4766979
  55. WINUTHAYANON W HEWITT SC ORVIS GD BEHRINGER RR KORACH KS Uterine epithelial estrogen receptor α is dispensable for proliferation but essential for complete biological and biochemical responses Proc Natl Acad Sci U S A 2010 107 19272 19277 20974921 PMC2984169
  56. WU X HOWARD MJ Transcripts encoding HAND genes are differentially expressed and regulated by BMP4 and GDNF in developing avian gut Gene Expr 2002 10 279 293 12450220 PMC5977526
  57. XIE H WANG H TRANGUCH S IWAMOTO R MEKADA E DEMAYO FJ LYDON JP DAS SK DEY SK Maternal heparin-binding-EGF deficiency limits pregnancy success in mice Proc Natl Acad Sci U S A 2007 104 18315 18320 17986609 PMC2084340
  58. YANG ZM LE SP CHEN DB COTA J SIERO V YASUKAWA K HARPER MJ Leukemia inhibitory factor, LIF receptor, and gp130 in the mouse uterus during early pregnancy Mol Reprod Dev 1995 42 407 414 8607969
  59. ZHU L POLLARD JW Estradiol-17beta regulates mouse uterine epithelial cell proliferation through insulin-like growth factor 1 signaling Proc Natl Acad Sci U S A 2007 104 15847 15851 17895382 PMC2000402

Cited by

Sorted by citations

Authors
Hantak, A. M., Bagchi, I. C., & Bagchi, M. K.
Affiliations
University of Illinois Urbana-Champaign (US)
Corresponding author
Bagchi, Milan K.
ORCID
Venue
The International Journal of Developmental Biology
Publisher
EHU Press
Published
2014
Volume
58
Issue
2-3-4
Pages
139-146
ISSN
0214-6282 (ISSN-L)
DOI
10.1387/ijdb.130348mb
PMC
PMC4768910
OpenAlex
W1965853166
Cited by
112
References
2
Citations by year
2026: 8 · 2025: 14 · 2024: 8 · 2023: 9 · 2022: 15 · 2021: 9 · 2020: 13 · 2019: 8 · 2018: 5 · 2017: 13 · 2016: 6 · 2015: 4
FWCI
3.50
Type
journal article
Language
en
Open access
Locations
  • The International Journal of Developmental Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Environmental Health Sciences (T32ES007326)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD055787)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
Keywords
embryo implantation, uterine stroma, luminal epithelium, stromal-epithelial crosstalk, decidua formation, paracrine signaling, estrogen, progesterone, implantation failure, infertility, genetically engineered mouse models, signaling pathways
MeSH terms
Animals, Embryo, Mammalian, Epithelial Cells, Female, Humans, Embryo Implantation, Pregnancy, Uterus, Stromal Cells, Receptor Cross-Talk, Mice

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