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BOR - Papers in Press, published online ahead of print November 24, 2004.
Biol Reprod 2004, 10.1095/biolreprod.104.034975
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BIOLOGY OF REPRODUCTION 72, 727–735 (2005)
DOI: 10.1095/biolreprod.104.034975
© 2005 by the Society for the Study of Reproduction, Inc.

Apoptosis Contributes to Vascular Lumen Formation and Vascular Branching in Human Placental Vasculogenesis1

Fatma Tertemiz3, Umit A. Kayisli2,3,4, Aydin Arici4, and Ramazan Demir3

Department of Histology and Embryology Faculty of Medicine,3 Akdeniz University, Antalya 07070, Turkey Department of Obstetrics and Gynecology,4 Yale University, School of Medicine, New Haven, Connecticut 06520-8063

Placental vasculogenesis consists of several stages, including appearance of hemangioblasts and angiogenic cell islands, setting up a primitive vascular network, and transition from vasculogenesis to sprouting and nonsprouting angiogenesis. In the present study, we hypothesized that placental vasculogenesis and angiogenesis require apoptosis during the formation of primitive vascular pattern, vessel elongation, and angiogenic branching. Vasculogenesis and apoptotic cells were identified using CD31 immunohistochemistry, hematoxylin-eosin (H-E) staining, CD31-TUNEL double-labeling, and transmission-electron microscopy (TEM). No TUNEL-positive cell was detected in angiogenic cell islands; however, several TUNEL-positive cells were observed during the primitive lumen formation. Interestingly, some of the stromal cells located between vasculogenic areas during the endothelial tube elongation and angiogenic branching also were TUNEL-positive. The presence of morphological aspects of apoptosis, such as nuclear shrinkage and nuclear bodies (apoptotic bodies), also was confirmed in H-E-stained and TEM-depicted sections. Quantitative analysis showed that higher ratios for apoptotic cells were found in the core stroma of villi among the vascular branching areas and in the primitive capillary lumen compared to angiogenic cell cords and vasculatures with advanced lumens (P < 0.05). In conclusion, our results suggest that apoptosis likely is involved in the physiologic mechanisms of placental vasculogenesis and angiogenesis, such as lumen formation and angiogenic branching.

1 Supported by Akdeniz University Scientific Research Project Units.

2 Correspondence: Umit A. Kayisli, Department of Histology and Embryology Faculty of Medicine, Akdeniz University, Antalya 07070, Turkey. FAX: 90 242 227 4486; uali{at}akdeniz.edu.tr




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