VEGFR-3 Neutralization Inhibits Ovarian Lymphangiogenesis, Follicle Maturation, and Murine Pregnancy
Identifieur interne : 003005 ( Main/Exploration ); précédent : 003004; suivant : 003006VEGFR-3 Neutralization Inhibits Ovarian Lymphangiogenesis, Follicle Maturation, and Murine Pregnancy
Auteurs : Joseph M. Rutkowski [Suisse] ; Jong Eun Ihm [Suisse] ; Seung Tae Lee [Suisse] ; Witold W. Kilarski [Suisse] ; Veronique I. Greenwood [Suisse] ; Miriella C. Pasquier [Suisse] ; Alexandra Quazzola [Suisse] ; Didier Trono [Suisse] ; Jeffrey A. Hubbell [Suisse] ; Melody A. Swartz [Suisse]Source :
- The American Journal of Pathology [ 0002-9440 ] ; 2013.
Abstract
Lymphatic vessels surround follicles within the ovary, but their roles in folliculogenesis and pregnancy, as well as the necessity of lymphangiogenesis in follicle maturation and health, are undefined. We used systemic delivery of mF4-31C1, a specific antagonist vascular endothelial growth factor receptor 3 (VEGFR-3) antibody to block lymphangiogenesis in mice. VEGFR-3 neutralization for 2 weeks before mating blocked ovarian lymphangiogenesis at all stages of follicle maturation, most notably around corpora lutea, without significantly affecting follicular blood angiogenesis. The numbers of oocytes ovulated, fertilized, and implanted in the uterus were normal in these mice; however, pregnancies were unsuccessful because of retarded fetal growth and miscarriage. Fewer patent secondary follicles were isolated from treated ovaries, and isolated blastocysts exhibited reduced cell densities. Embryos from VEGFR-3–neutralized dams developed normally when transferred to untreated surrogates. Conversely, normal embryos transferred into mF4-31C1–treated dams led to the same fetal deficiencies observed with
Url:
DOI: 10.1016/j.ajpath.2013.07.031
PubMed: 24036251
PubMed Central: 3814520
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en"><p>Lymphatic vessels surround follicles within the ovary, but their roles in folliculogenesis and pregnancy, as well as the necessity of lymphangiogenesis in follicle maturation and health, are undefined. We used systemic delivery of mF4-31C1, a specific antagonist vascular endothelial growth factor receptor 3 (VEGFR-3) antibody to block lymphangiogenesis in mice. VEGFR-3 neutralization for 2 weeks before mating blocked ovarian lymphangiogenesis at all stages of follicle maturation, most notably around corpora lutea, without significantly affecting follicular blood angiogenesis. The numbers of oocytes ovulated, fertilized, and implanted in the uterus were normal in these mice; however, pregnancies were unsuccessful because of retarded fetal growth and miscarriage. Fewer patent secondary follicles were isolated from treated ovaries, and isolated blastocysts exhibited reduced cell densities. Embryos from VEGFR-3–neutralized dams developed normally when transferred to untreated surrogates. Conversely, normal embryos transferred into mF4-31C1–treated dams led to the same fetal deficiencies observed with <italic>in situ</italic>
gestation. Although no significant changes were measured in uterine blood or lymphatic vascular densities, VEGFR-3 neutralization reduced serum and ovarian estradiol concentrations during gestation. VEGFR-3–mediated lymphangiogenesis thus appears to modulate the folliculogenic microenvironment and may be necessary for maintenance of hormone levels during pregnancy; both of these are novel roles for the lymphatic vasculature.</p>
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<name sortKey="Ihm, Jong Eun" sort="Ihm, Jong Eun" uniqKey="Ihm J" first="Jong Eun" last="Ihm">Jong Eun Ihm</name>
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<name sortKey="Lee, Seung Tae" sort="Lee, Seung Tae" uniqKey="Lee S" first="Seung Tae" last="Lee">Seung Tae Lee</name>
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