VEGFR-3 neutralization inhibits ovarian lymphangiogenesis, follicle maturation, and murine pregnancy

Joseph M. Rutkowski, Jong Eun Ihm, Seung Tae Lee, Witold W. Kilarski, Veronique I. Greenwood, Miriella C. Pasquier, Alexandra Quazzola, Didier Trono, Jeffrey A. Hubbell, Melody A. Swartz

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 in situ 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.

Original languageEnglish (US)
Pages (from-to)1596-1607
Number of pages12
JournalAmerican Journal of Pathology
Volume183
Issue number5
DOIs
StatePublished - Nov 2013

Fingerprint

Vascular Endothelial Growth Factor Receptor-3
Lymphangiogenesis
Ovarian Follicle
Pregnancy
Ovary
Embryonic Structures
Lymphatic Vessels
Corpus Luteum
Blastocyst
Spontaneous Abortion
Fetal Development
Uterus
Oocytes
Blood Vessels
Estradiol
Cell Count
Maintenance
Hormones
Antibodies
Health

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Rutkowski, J. M., Ihm, J. E., Lee, S. T., Kilarski, W. W., Greenwood, V. I., Pasquier, M. C., ... Swartz, M. A. (2013). VEGFR-3 neutralization inhibits ovarian lymphangiogenesis, follicle maturation, and murine pregnancy. American Journal of Pathology, 183(5), 1596-1607. https://doi.org/10.1016/j.ajpath.2013.07.031

VEGFR-3 neutralization inhibits ovarian lymphangiogenesis, follicle maturation, and murine pregnancy. / Rutkowski, Joseph M.; Ihm, Jong Eun; Lee, Seung Tae; Kilarski, Witold W.; Greenwood, Veronique I.; Pasquier, Miriella C.; Quazzola, Alexandra; Trono, Didier; Hubbell, Jeffrey A.; Swartz, Melody A.

In: American Journal of Pathology, Vol. 183, No. 5, 11.2013, p. 1596-1607.

Research output: Contribution to journalArticle

Rutkowski, JM, Ihm, JE, Lee, ST, Kilarski, WW, Greenwood, VI, Pasquier, MC, Quazzola, A, Trono, D, Hubbell, JA & Swartz, MA 2013, 'VEGFR-3 neutralization inhibits ovarian lymphangiogenesis, follicle maturation, and murine pregnancy', American Journal of Pathology, vol. 183, no. 5, pp. 1596-1607. https://doi.org/10.1016/j.ajpath.2013.07.031
Rutkowski, Joseph M. ; Ihm, Jong Eun ; Lee, Seung Tae ; Kilarski, Witold W. ; Greenwood, Veronique I. ; Pasquier, Miriella C. ; Quazzola, Alexandra ; Trono, Didier ; Hubbell, Jeffrey A. ; Swartz, Melody A. / VEGFR-3 neutralization inhibits ovarian lymphangiogenesis, follicle maturation, and murine pregnancy. In: American Journal of Pathology. 2013 ; Vol. 183, No. 5. pp. 1596-1607.
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