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Effects of obesogenic diet on uterine natural killer cell function and vascular remodeling in pregnancy in mice Baltayeva, Jennet

Abstract

Pre-pregnancy obesity associates with adverse reproductive outcomes that impact maternal and fetal health. While obesity-driven mechanisms underlying adverse pregnancy outcomes remain unclear, local uterine immune cells are strong but poorly studied candidates. Uterine immune cells, particularly uterine natural killer cells (uNK), play central roles in orchestrating developmental events in pregnancy. However, the effect of obesity on uNK biology is poorly understood. Using an obesogenic high fat/high sugar diet (HFD) mouse model, I set out to examine the effects of maternal obesity on uNK composition and establishment of the maternal-fetal interface. HFD exposure resulted in weight gain-dependent increases in systemic inflammation and rates of fetal resorption. While HFD did not affect total uNK proprotions, HFD exposure led to an increase in natural cytotoxicity triggering receptor-1 (Ncr1) expressing uNKs as well as overall uNK activity. Importantly, HFD-associated changes in uNK coincided with impairments in uterine artery remodeling in mid-pregnancy, but these vascular alterations were no longer observed by late pregnancy. Comparison of uNK mRNA transcripts from control and HFD mice identified HFD-directed transcriptional changes in genes that play roles in promoting activity/cytotoxicity and vascular biology. Together, this work provides new insight into how obesity may impact uNK-processes central to the establishment of the maternal-fetal interface in early and mid-pregnancy. Moreover, these findings shed light on the cellular processes affected by maternal obesity that may relate to overall pregnancy health.

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Attribution-NonCommercial-NoDerivatives 4.0 International

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