Abstract
BackgroundNeovascularization is necessary for follicular growth. Vascularization is first observed in preantral follicles, and thereafter the vasculature markedly increases in follicles undergoing development. Neovascularization includes angiogenesis and vasculogenesis. Vasculogenesis is the formation of new blood vessels by bone marrow-derived endothelial progenitor cells. It is unclear whether vasculogenesis occurs during follicular growth. Blood vessels must be mature to be functional blood vessels. Mature blood vessels are characterized by the recruitment of pericytes. However, it is unclear where pericytes come from and whether they contribute to neovascularization in the follicle during follicular growth. In this study, we investigated whether bone marrow-derived progenitor cells that differentiate into vascular endothelial cells or pericytes contribute to neovascularization during follicular growth.MethodsA parabiosis model was used in this study. Six-week-old wild-type and transgenic female mice expressing green fluorescent protein (GFP) were conjoined between the lateral abdominal regions to create a shared circulatory system. After 6 weeks, the ovaries were obtained and immunostained for CD31/CD34 (a vascular endothelial cell marker), platelet-derived growth factor receptor-β (PDGFR-β) (a pericyte marker), and GFP (a bone marrow-derived cell marker).ResultsCells that were positive for CD34 and PDGFR-β were observed in the stroma adjacent to the primary or early preantral follicles and in the theca cell layer of the follicles from the late preantral stage to the preovulatory stage. CD31/CD34 and GFP double-positive cells were observed in the theca cell layer of the follicle from the antral stage to the preovulatory stage while the number of double-positive cells in the preovulatory follicles did not increase. PDGFR-β and GFP double-positive cells were observed in the theca cell layer of the preovulatory follicle but not in the smaller follicle.ConclusionsLocally existing endothelial cells and pericytes in the stroma play a central role in the neovascularization during follicular growth, while bone marrow-derived endothelial cells and pericytes partially contribute to this process.
Highlights
IntroductionVasculogenesis is the formation of new blood vessels by bone marrow-derived endothelial progenitor cells
CD34-positive cells and platelet-derived growth factor receptor-β (PDGFR-β)-positive cells were observed in the stroma adjacent to the primary or early preantral follicle
These findings indicate the presence of bone marrow-derived vascular endothelial cells around the preantral follicle and in the theca cell layer of the antral and preovulatory follicles
Summary
Vasculogenesis is the formation of new blood vessels by bone marrow-derived endothelial progenitor cells. It is unclear whether vasculogenesis occurs during follicular growth. Mature blood vessels are characterized by the recruitment of pericytes It is unclear where pericytes come from and whether they contribute to neovascularization in the follicle during follicular growth. We investigated whether bone marrow-derived progenitor cells that differentiate into vascular endothelial cells or pericytes contribute to neovascularization during follicular growth. Suppression of angiogenesis in preantral and early-antral follicles causes follicular atresia at these follicular developmental stages [4]. Vascular development plays a crucial role in the selection and maturation of the dominant follicle destined to ovulate during the late follicular developmental stage [1]. Inhibition of angiogenesis in the late follicular phase interferes with the final stage of follicular development and delays ovulation [5,6]
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