Pregnancy Augments the Vasoactive, Metabolic, and Inflammatory Functions of Uterine Perivascular Adipose Tissue

Introduction: Perivascular adipose tissue (PVAT) is functionally different from other adipose depots and has vasoactive effects that vary with anatomic location and disease state. Healthy pregnancy involves remodeling of the vessels that supply blood flow to the uteroplacental unit (i.e. uterine arteries) and increases adipose tissue metabolic and inflammatory functions. The main objective of this study was to examine whether pregnancy changes the function of PVAT surrounding the uterine arteries (utPVAT). Hypothesis: Healthy pregnancy augments the vasoactive, metabolic, and inflammatory functions of utPVAT. Methods: Pregnant (gestational day 16, term=22-23 days) and aged-matched non-pregnant rats were used. To evaluate the effects of utPVAT on endothelium-dependent dilation in uterine artery, we performed concentration-response curves to acetylcholine (ACh) in the presence or absence of utPVAT using wire myography. A proteome adipokine profiler and reverse transcription polymerase chain reaction (RT-PCR) were used to assess protein and gene expression of utPVAT adipocytokines, respectively. Results: Incubation of uterine arteries from pregnant rats with utPVAT reduced ACh-induced relaxation responses following constriction with 60 mM potassium chloride solution [pEC50, +PVAT (n=5): 6.25 ± 0.12 vs. –PVAT (n=5): 6.66 ± 0.18, p = 0.02] or 10-6 M phenylephrine [pEC50, +PVAT (n=9): 6.86 ± 0.10 vs. –PVAT (n=9): 7.61 ± 0.17, p=0.0004]. This effect was not seen in arteries from non-pregnant animals. Uterine PVAT from pregnant rats (n=3) had reduced mRNA expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) by 5.7 fold compared to utPVAT from non-pregnant rats (n=4). Leptin mRNA expression was reduced by 6.4 fold and protein expression was increased in utPVAT from pregnant rats compared to utPVAT from non-pregnant rats. Interleukin (IL)-10, IL-6, and monocyte chemoattractant protein (MCP)-1 mRNA expression in utPVAT did not differ between groups but protein expression of these adipocytokines was increased in utPVAT from pregnant rats. Conclusion: In pregnancy, utPVAT reduces endothelium-dependent relaxation in uterine arteries. In addition, pregnancy regulates metabolic and inflammatory adipocytokines in utPVAT at the level of protein translation. Future studies will determine the functional role of the vasoactive and molecular changes in utPVAT and their impact on uterine blood flow and fetal growth.