In vitro and in vivo evidence for lack of endovascular remodeling by third trimester trophoblasts.
The placental-decidual interaction through invading trophoblasts determines whether a physiological transformation of the uterine spiral arteries is established or not. Trophoblast-orchestrated artery remodeling is central to normal placentation. Dysregulated uteroplacental interaction and vascular remodeling are thought to be associated with the molecular events underlying the pathology of late pregnancy anomalies including preeclampsia. Although the exact gestational age at which trophoblast invasion ceases is not known, it remains unclear whether late pregnancy trophoblasts retain the ability to transform the uterine arteries. Here, we have developed a dual cell, in vitro culture system that mimics the vascular remodeling events during normal pregnancy. We demonstrate that first and third trimester trophoblasts respond differentially to interactive signals from endothelial cells when cultured on matrigel. Term primary trophoblasts or immortalized third trimester extravillous TCL1 trophoblasts not only fail to respond to signals from endothelial cells but also inhibit endothelial cell tube formation. In contrast, HTR8 cells, representing a first trimester trophoblast cell line with invasive properties, undergo spontaneous migration and synchronize with the endothelial cells in a capillary network. This disparity in behavior was confirmed in vivo using a matrigel plug assay. Poor expression of VEGF C and VEGF receptors coupled with high E-cadherin expression by term primary trophoblasts and TCL1 cells contributed to their restricted interactive and migratory properties. We further show that the kinase activity of VEGF R2 is essential for proactive crosstalk by HTR8 cells. This unique behavior of first trimester trophoblasts in the presence of endothelial cells offers a potential approach to study cell-cell interactions and to decipher modulatory components in the serum samples from adverse pregnancy outcomes.
Kalkunte
S
S
Department of Pediatrics, Women and Infants Hospital, 101 Dudley Street, Providence, RI 02905, USA.
Lai
Z
Z
Tewari
N
N
Chichester
C
C
Romero
R
R
Padbury
J
J
Sharma
S
S
D015703:Antigens, CD / Q000096:biosynthesis; D001158:Arteries / Q000502:physiology*; D015820:Cadherins / Q000096:biosynthesis; D002460:Cell Line; D018920:Coculture Techniques; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D005260:Female; D006801:Humans; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000502:physiology; D011263:Pregnancy Trimester, Third / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D014327:Trophoblasts / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis
D015703:Antigens, CD; D015820:Cadherins; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1
Placenta. 2000 Sep;21(7):693-702
10985973
Acta Obstet Gynecol Scand. 2003 Aug;82(8):722-9
12848643
N Engl J Med. 2004 Feb 12;350(7):672-83
14764923
Am J Reprod Immunol. 2008 Jan;59(1):75-83
18154598
J Immunol. 2000 Jun 1;164(11):5721-8
10820249
Hypertension. 2007 Jul;50(1):35-6
17515451
Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H541-50
18055511
Placenta. 1996 Mar-Apr;17(2-3):137-46
8730883
Am J Obstet Gynecol. 2003 Jan;188(1):177-82
12548214
Am J Reprod Immunol. 2007 Aug;58(2):98-110
17631003
J Reprod Immunol. 2004 Dec;64(1-2):9-29
15596224
Gynecol Oncol. 2001 Jul;82(1):162-6
11426979
Exp Cell Res. 1993 Jun;206(2):204-11
7684692
Arterioscler Thromb Vasc Biol. 2001 Dec;21(12):1934-40
11742867
Hum Reprod. 1999 Aug;14(8):2131-8
10438439
Nat Med. 2006 Jun;12(6):642-9
16751767
Placenta. 1983 Oct-Dec;4(4):397-413
6634666
Biol Reprod. 2005 Aug;73(2):237-43
15800179
J Clin Endocrinol Metab. 2004 May;89(5):2484-90
15126581
Dev Biol. 2003 Nov 1;263(1):114-25
14568550
Placenta. 2002 Jan;23(1):3-19
11869088
Am J Obstet Gynecol. 2003 Oct;189(4):1063-9
14586356
J Biol Chem. 2004 Feb 13;279(7):5716-24
14625306
Nat Rev Cancer. 2005 Sep;5(9):675-88
16148884
Biol Reprod. 1998 Dec;59(6):1540-8
9828203
Endocrinology. 2006 Nov;147(11):5275-83
16887905
Trends Cell Biol. 2005 Jan;15(1):19-26
15653074
Cell Tissue Res. 1988 Jul;253(1):231-40
3416340
Exp Cell Res. 2005 Feb 1;303(1):101-13
15572031
Nat Med. 2006 Sep;12(9):1065-74
16892062
Mol Hum Reprod. 2000 Jan;6(1):88-95
10611266
J Clin Invest. 1997 May 1;99(9):2139-51
9151786
J Perinat Med. 2006;34(6):447-58
17140293
Am J Pathol. 2002 Apr;160(4):1405-23
11943725
Mol Cell Biol. 2005 Jan;25(1):355-63
15601856