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Maternal obesity drives functional alterations in uterine NK cells
Sofie Perdu, … , Lauren DeLuca, Alexander G. Beristain
Sofie Perdu, … , Lauren DeLuca, Alexander G. Beristain
Published July 21, 2016
Citation Information: JCI Insight. 2016;1(11):e85560. https://doi.org/10.1172/jci.insight.85560.
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Research Article Immunology Reproductive biology

Maternal obesity drives functional alterations in uterine NK cells

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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

Sofie Perdu, Barbara Castellana, Yoona Kim, Kathy Chan, Lauren DeLuca, Alexander G. Beristain

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Figure 1

Maternal obesity is associated with low-grade chronic inflammation.

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Maternal obesity is associated with low-grade chronic inflammation.
(A) ...
(A) Relationship between serum C-reactive protein (CRP) and BMI shown graphically as a line amongst 90 women in early pregnancy. The horizontal line indicates the CRP threshold (3 μg/ml), indicative of low-grade inflammation. The blue hashed box indicates control (lean) BMI samples having CRP values < 3 μg/ml; the red hashed box indicates obese BMI samples having CRP values ≥ 3 μg/ml. r2 = the coefficient of determination. (B) Relationship between serum leptin and BMI shown graphically as a line. (C) Pie chart depicting proportions of control and obese BMI women presenting with/without elevated serum CRP. (D) Linear regression analysis showing the relationship between serum CRP and leptin between control and obese BMI women. Shown are the 95% confidence interval (95% CI) and the coefficient of determination (r2). P < 0.0001, linear regression statistics.

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