Top

Published in:

Open Access 01-12-2014 | Research

Locally existing endothelial cells and pericytes in ovarian stroma, but not bone marrow-derived vascular progenitor cells, play a central role in neovascularization during follicular development in mice

Authors: Fumie Kizuka-Shibuya, Nobuko Tokuda, Kiyoshi Takagi, Yasuhiro Adachi, Lifa Lee, Isao Tamura, Ryo Maekawa, Hiroshi Tamura, Takashi Suzuki, Yuji Owada, Norihiro Sugino

Published in: Journal of Ovarian Research | Issue 1/2014

Abstract

Background

Neovascularization 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.

Methods

A 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).

Results

Cells 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.

Conclusions

Locally 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.

Available only for authorised users

Zimmermann RC, Xiao E, Bohlen P, Ferin M: Administration of antivascular endothelial growth factor receptor 2 antibody in the early follicular phase delays follicular selection and development in the rhesus monkey. Endocrinology 2002, 143: 2496–2502.CrossRefPubMed

Danforth DR, Arbogast LK, Ghosh S, Dickerman A, Rofagha R, Friedman CI: Vascular endothelial growth factor stimulates preantral follicle growth in the rat ovary. Biol Reprod 2003, 68: 1736–1741.CrossRefPubMed

Wulff C, Wilson H, Wiegand SJ, Rudge JS, Fraser HM: Prevention of thecal angiogenesis, antral follicular growth, and ovulation in the primate by treatment with vascular endothelial growth factor trap R1R2. Endocrinology 2002, 143: 2797–2807.CrossRefPubMed

Garside SA, Henkin J, Morris KD, Norvell SM, Thomas FH, Fraser HM: A thrombospondin-mimetic peptide, ABT-898, suppresses angiogenesis and promotes follicular atresia in pre- and early-antral follicles in vivo. Endocrinology 2010, 151: 5905–5915. 10.1210/en.2010-0283CrossRefPubMed

Zimmermann RC, Xiao E, Husami N, Sauer MV, Lobo R, Kitajewski J, Ferin M: Short-term administration of antivascular endothelial growth factor antibody in the late follicular phase delays follicular development in the rhesus monkey. J Clin Endocrinol Metab 2001, 86: 768–772.PubMed

Zimmermann RC, Hartman T, Kavic S, Pauli SA, Bohlen P, Sauer MV, Kitajewski J: Vascular endothelial growth factor receptor 2-mediated angiogenesis is essential for gonadotropin-dependent follicle developmen. J Clin Invest 2003, 112: 659–669.PubMedCentralCrossRefPubMed

Findlay JK: Angiogenesis in reproductive tissues. J Endocrinol 1986, 111: 357–366. 10.1677/joe.0.1110357CrossRefPubMed

Fraser HM: Regulation of the ovarian follicular vasculature. Rev Reprod Biol Endocrinol 2006, 4: 18. 10.1186/1477-7827-4-18CrossRef

Wulff C, Wiegand SJ, Saunders PT, Scobie GA, Fraser HM: Angiogenesis during follicular development in the primate and its inhibition by treatment with truncated Flt-1-Fc (vascular endothelial growth factor Trap (A40)). Endocrinology 2001, 142: 3244–3254.PubMed

10.

Kizuka F, Tokuda N, Takagi K, Adachi Y, Lee L, Tamura I, Maekawa R, Taketani T, Tamura H, Suzuki T, Owada Y, Sugino N: Involvement of bone marrow-derived vascular progenitor cells in neovascularization during formation of the corpus luteum in mice. Biol Reprod 2012,87(3):55. 10.1095/biolreprod.112.099960CrossRefPubMed

11.

Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM: Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997, 275: 964–967. 10.1126/science.275.5302.964CrossRefPubMed

12.

Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM: Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999, 85: 221–228. 10.1161/01.RES.85.3.221CrossRefPubMed

13.

Sugino N, Suzuki T, Sakata A, Miwa I, Asada H, Taketani T, Yamagata Y, Tamura H: Angiogenesis in the human corpus luteum: changes in expression of angiopoietins in the corpus luteum throughout the menstrual cycle and in early pregnancy. J Clin Endocrinol Metab 2005, 90: 6141–6148. 10.1210/jc.2005-0643CrossRefPubMed

14.

Sugino N, Matsuoka A, Taniguchi K, Tamura H: Angiogenesis in the human corpus luteum. Reprod Med Biol 2008, 7: 91–103. 10.1111/j.1447-0578.2008.00205.xCrossRef

15.

Matsuoka-Sakata A, Tamura H, Asada H, Miwa I, Taketani T, Yamagata Y, Sugino N: Changes in vascular leakage and expression of angiopoietins in the corpus luteum during pregnancy in rats. Reproduction 2006, 131: 351–360. 10.1530/rep.1.00947CrossRefPubMed

16.

Chang CC, Lerman OZ, Thanik VD, Scharf CL, Greives MR, Schneider RJ, Formenti SC, Saadeh PB, Warren SM, Levine JP: Dose-dependent effect of radiation on angiogenic and angiostatic CXC chemokine expression in human endothelial cells. Cytokine 2009, 48: 295–302. 10.1016/j.cyto.2009.08.007CrossRefPubMed

17.

Kozin SV, Kamoun WS, Huang Y, Dawson MR, Jain RK, Duda DG: Recruitment of myeloid but not endothelial precursor cells facilitates tumor regrowth after local irradiation. Cancer Res 2010, 70: 5679–5685. 10.1158/0008-5472.CAN-09-4446PubMedCentralCrossRefPubMed

18.

Wright DE, Wagers AJ, Gulati AP, Johnson FL, Weissman IL: Physiological migration of hematopoietic stem and progenitor cells. Science 2001, 294: 1933–1936. 10.1126/science.1064081CrossRefPubMed

19.

Tanaka K, Sata M, Natori T, Kim-Kaneyama JR, Nose K, Shibanuma M, Hirata Y, Nagai R: Circulating progenitor cells contribute to neointimal formation in nonirradiated chimeric mice. FASEB J 2008, 22: 428–436.CrossRefPubMed

20.

Owada Y, Abdelwahab SA, Kitanaka N, Sakagami H, Takano H, Sugitani Y, Sugawara M, Kawashima H, Kiso Y, Mobarakeh JI, Yanai K, Kaneko K: Altered emotional behavioral responses in mice lacking brain-type fatty acid-binding protein gene. Eur J Neurosci 2006, 24: 175–187. 10.1111/j.1460-9568.2006.04855.xCrossRefPubMed

21.

Song S, Ewald AJ, Stallcup W, Werb Z, Bergers G: PDGFRbeta + perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival. Nat Cell Biol 2005, 7: 870–879. 10.1038/ncb1288PubMedCentralCrossRefPubMed

22.

Suzuki T, Sasano H, Takaya R, Fukaya T, Yajima A, Nagura H: Cyclic changes of vasculature and vascular phenotypes in normal human ovaries. Hum Reprod 1998, 13: 953–959. 10.1093/humrep/13.4.953CrossRefPubMed

23.

Butcher RL, Kirkpatrick-Keller D: Pattern of follicular growth during the four-day estrous cycle of the rat. Biol Reprod 1984, 31: 280–286. 10.1095/biolreprod31.2.280CrossRefPubMed

24.

Masuda H, Kalka C, Takahashi T, Yoshida M, Wada M, Kobori M, Itoh R, Iwaguro H, Eguchi M, Iwami Y, Tanaka R, Nakagawa Y: Estrogen-mediated endothelial progenitor cell biology and kinetics for physiological postnatal vasculogenesis. Circ Res 2007, 101: 598–606. 10.1161/CIRCRESAHA.106.144006CrossRefPubMed

25.

Alev C, Ii M, Asahara T: Endothelial progenitor cells: a novel tool for the therapy of ischemic diseases. Antioxid Redox Signal 2011, 15: 949–965. 10.1089/ars.2010.3872CrossRefPubMed

26.

Ii M, Nishimura H, Iwakura A, Wecker A, Eaton E, Asahara T, Losordo DW: Endothelial progenitor cells are rapidly recruited to myocardium and mediate protective effect of ischemic preconditioning via “imported” nitric oxide synthase activity. Circulation 2005, 111: 1114–1120. 10.1161/01.CIR.0000157144.24888.7ECrossRefPubMed

27.

Krenning G, van Luyn MJ, Harmsen MC: Endothelial progenitor cell-based neovascularization: implications for therapy. Trends Mol Med 2009, 15: 180–189. 10.1016/j.molmed.2009.02.001CrossRefPubMed

28.

Kuhnert F, Tam BY, Sennino B, Gray JT, Yuan J, Jocson A, Nayak NR, Mulligan RC, McDonald DM, Kuo CJ: Soluble receptor-mediated selective inhibition of VEGFR and PDGFRbeta signaling during physiologic and tumor angiogenesis. Proc Natl Acad Sci U S A 2008, 105: 10185–10190. 10.1073/pnas.0803194105PubMedCentralCrossRefPubMed

29.

Redmer DA, Doraiswamy V, Bortnem BJ, Fisher K, Jablonka-Shariff A, Grazul-Bilska AT, Reynolds LP: Evidence for a role of capillary pericytes in vascular growth of the developing ovine corpus luteum. Biol Reprod 2001, 65: 879–889. 10.1095/biolreprod65.3.879CrossRefPubMed

30.

Tigges U, Hyer EG, Scharf J, Stallcup WB: FGF2-dependent neovascularization of subcutaneous matrigel plugs is initiated by bone marrow-derived pericytes and macrophages. Development 2008, 135: 523–532. 10.1242/dev.002071CrossRefPubMed

Title: Locally existing endothelial cells and pericytes in ovarian stroma, but not bone marrow-derived vascular progenitor cells, play a central role in neovascularization during follicular development in mice
Authors: Fumie Kizuka-Shibuya
Nobuko Tokuda
Kiyoshi Takagi
Yasuhiro Adachi
Lifa Lee
Isao Tamura
Ryo Maekawa
Hiroshi Tamura
Takashi Suzuki
Yuji Owada
Norihiro Sugino
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Journal of Ovarian Research / Issue 1/2014
Electronic ISSN: 1757-2215
DOI: https://doi.org/10.1186/1757-2215-7-10

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Locally existing endothelial cells and pericytes in ovarian stroma, but not bone marrow-derived vascular progenitor cells, play a central role in neovascularization during follicular development in mice

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2014

Brachial-to-ankle pulse wave velocity as an independent prognostic factor for ovulatory response to clomiphene citrate in women with polycystic ovary syndrome

A pilot study to search possible mechanisms of ultralong gonadotropin-releasing hormone agonist therapy in IVF-ET patients with endometriosis

Lipid index changes in the blood serum of patients with hyperplastic and early neoplastic lesions in the ovaries

In vivo fate mapping of cryopreserved murine ovarian grafts

microRNA 490-3P enhances the drug-resistance of human ovarian cancer cells

Evaluation of the ovarian reserve function in patients with metabolic syndrome in relation to healthy controls and different age groups