title: Maternal obesity drives functional alterations in uterine NK cells.
abstract: Over one-fifth of North American women of childbearing age are obese, putting these women at risk for a variety of detrimental chronic diseases. In addition, obesity increases the risk for developing major complications during pregnancy. The mechanisms by which obesity contributes to pregnancy complications and loss remain unknown. Increasing evidence indicates that obesity results in major changes to adipose tissue immune cell composition and function; whether or not obesity also affects immune function in the uterus has not been explored. Here we investigated the effect of obesity on uterine natural killer (uNK) cells, which are essential for uterine artery remodeling and placental development. Using a cohort of obese or lean women, we found that obesity led to a significant reduction in uNK cell numbers accompanied with impaired uterine artery remodeling. uNK cells isolated from obese women had altered expression of genes and pathways associated with extracellular matrix remodeling and growth factor signaling. Specifically, uNK cells were hyper-responsive to PDGF, resulting in overexpression of decorin. Functionally, decorin strongly inhibited placental development by limiting trophoblast survival. Together, these findings establish a potentially new link between obesity and poor pregnancy outcomes, and indicate that obesity-driven changes to uterine-resident immune cells critically impair placental development.
authors.affiliation: The Child and Family Research Institute, Vancouver, Canada.
authors.forename: Sofie
authors.initials: S
authors.lastname: Perdu
authors.affiliation: The Child and Family Research Institute, Vancouver, Canada.|Department of Obstetrics and Gynecology and the.
authors.forename: Barbara
authors.initials: B
authors.lastname: Castellana
authors.affiliation: The Child and Family Research Institute, Vancouver, Canada.
authors.forename: Yoona
authors.initials: Y
authors.lastname: Kim
authors.affiliation: The Child and Family Research Institute, Vancouver, Canada.
authors.forename: Kathy
authors.initials: K
authors.lastname: Chan
authors.affiliation: The Child and Family Research Institute, Vancouver, Canada.|Experimental Medicine Graduate Program, The University of British Columbia, Vancouver, Canada.
authors.forename: Lauren
authors.initials: L
authors.lastname: DeLuca
authors.affiliation: The Child and Family Research Institute, Vancouver, Canada.|Department of Obstetrics and Gynecology and the.|Experimental Medicine Graduate Program, The University of British Columbia, Vancouver, Canada.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Beristain
mesh_terms: D000328:Adult; D024061:Collagen Type III / Q000378:metabolism; D058575:Decorin / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology*; D009765:Obesity / Q000503:physiopathology*; D010920:Placenta; D011247:Pregnancy; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D014327:Trophoblasts; D055988:Uterine Artery / Q000503:physiopathology*; D014599:Uterus / Q000166:cytology* / Q000276:immunology; D066253:Vascular Remodeling; D055815:Young Adult
chemical_list: C439971:COL3A1 protein, human; D024061:Collagen Type III; C546878:DCN protein, human; D058575:Decorin; D017479:Receptors, Platelet-Derived Growth Factor