title: Development and hormonal regulation of the ovarian lymphatic vasculature.
abstract: The lymphatic vasculature plays a number of essential physiological roles including maintaining fluid homeostasis, providing a network for the transport of immune cells, and facilitating the uptake of fat-soluble nutrients from the gastrointestinal tract. Although the critical importance and remodeling capacity of the blood vasculature has been well described within the ovary, just a few reports describe the lymphatic vasculature. Using histological and molecular techniques, we report the kinetics of ovarian lymphangiogenesis and the hormonal regulation of lymphangiogenic growth factors associated with key stages of ovarian follicle growth. We exploited the Adamts1-null mouse model, a model with a previously characterized lymphatic defect to further interrogate the mechanisms controlling ovarian lymphangiogenesis. The establishment and development of the ovarian lymphatic vascular network in postnatal developing ovaries was associated with the presence and hormonal regulation of the lymphangiogenic growth factors and their receptors, including Vegfc, Vegfd, and Vegfr3. We characterized the hormonally regulated remodeling of the ovarian lymphatic vasculature in response to FSH and estradiol. The lymphatic network was defective in the Adamts1-null ovary, clearly demonstrating both the involvement of FSH/estradiol and the Adamts1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) protease in ovarian lymphangiogenesis. This study provides the first evidence of a malleable lymphatic system responsive to hormonal changes of the female reproductive cycle, at least in the mouse ovary, suggesting a role for lymphatic vessel functions in normal folliculogenesis.
authors.affiliation: School of Pediatrics and Reproductive Health, Robinson Institute, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Brown
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Robker
authors.forename: Darryl L
authors.initials: DL
authors.lastname: Russell
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000071097:ADAMTS1 Protein; D000704:Analysis of Variance; D000818:Animals; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D007150:Immunohistochemistry; D042583:Lymphangiogenesis / Q000502:physiology*; D042601:Lymphatic Vessels / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D006080:Ovarian Follicle / Q000276:immunology / Q000378:metabolism; D010053:Ovary / Q000254:growth & development* / Q000276:immunology / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D040262:Receptors, Vascular Endothelial Growth Factor; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C486323:Adamts1 protein, mouse