The blood supply to the primate placenta is established by the conversion of the muscular spiral arteries into dilated funnel- shaped uteroplacental arteries whose walls are composed mainly of trophoblast cells and connective tissue. These changes are thought to accommodate the greater volume of blood flow required by the developing conceptus, and to modify the normal maternal control mechanisms of these vessels. It has been observed that pregnancies complicated by preeclampsia alone, or preeclampsia with essential hypertension, structural modification of the arterial walls is less extensive and this apparently compromises uteroplacental perfusion. The key element in the conversion of the arteries is the migration of endovascular cells, thought to be trophoblast, into the spiral arteries. The endothelium is apparently removed and this is followed by the destruction of the muscular arterial wall and its replacement by trophoblast and connective tissue. There are many gaps in our understanding of the development of the uteroplacental arteries in primates especially the cellular mechanisms by which the invasion, destruction and replacement are carried out. The long- term objective of this proposal is the characterize the process of invasion and modification of the spiral arteries in the rhesus monkey, a species with many placental anatomical similarities to the human.
Specific aims are 1) to define ultrastructurally and immunocytochemically the sequence of cellular interactions between endovascular trophoblast and endothelial cells during the initial invasion of the spiral arteries; 2) to determine the cellular mechanisms by which the endovascular trophoblast removes the maternal endothelium, penetrates the walls of the arteries and destroys the smooth muscle of the tunica media. At the present time, there is little information available on how this is accomplished in primates. Careful ultrastructural descriptions will be coupled with cytochemical studies to evaluate the role of lysosomal enzymes in this process, a role suggested by studies in other species; and 3) to determine, using immunocytochemical methods, the changes in the composition of the connective tissue components of the arterial wall during the conversion of the spiral arteries to the uteroplacental arteries.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD024491-04
Application #
3325111
Study Section
Special Emphasis Panel (SRC (MW))
Project Start
1988-03-01
Project End
1993-12-31
Budget Start
1991-03-01
Budget End
1993-12-31
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Enders, A C; Blankenship, T N (2012) Interstitial trophoblast cells: an enigmatic and variable component of the developing macaque placenta. Placenta 33:672-6
Enders, A C (2007) Implantation in the macaque: expansion of the implantation site during the first week of implantation. Placenta 28:794-802
Enders, A C; Blankenship, T N; Fazleabas, A T et al. (2001) Structure of anchoring villi and the trophoblastic shell in the human, baboon and macaque placenta. Placenta 22:284-303
Enders, A C (2000) Trophoblast-uterine interactions in the first days of implantation: models for the study of implantation events in the human. Semin Reprod Med 18:255-63
Douglas, G C; Thirkill, T L; Blankenship, T N (1999) Vitronectin receptors are expressed by macaque trophoblast cells and play a role in migration and adhesion to endothelium. Biochim Biophys Acta 1452:36-45
Blankenship, T N; Enders, A C (1997) Trophoblast cell-mediated modifications to uterine spiral arteries during early gestation in the macaque. Acta Anat (Basel) 158:227-36
Enders, A C; Blankenship, T N (1997) Modification of endometrial arteries during invasion by cytotrophoblast cells in the pregnant macaque. Acta Anat (Basel) 159:169-93
King, B F; Blankenship, T N (1997) Immunohistochemical localization of fibrillin in developing macaque and term human placentas and fetal membranes. Microsc Res Tech 38:42-51
Blankenship, T N; Enders, A C (1997) Expression of platelet-endothelial cell adhesion molecule-1 (PECAM) by macaque trophoblast cells during invasion of the spiral arteries. Anat Rec 247:413-9
Blankenship, T N; King, B F (1996) Macaque intra-arterial trophoblast and extravillous trophoblast of the cell columns and cytotrophoblastic shell express neural cell adhesion molecule (NCAM). Anat Rec 245:525-31

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