Chemerin Increases Contractility of the Uterine Artery and Leads to Placentomegalia

Abstract

Chemerin is an adipokine released from several tissues (mostly adipocytes but also placenta, ovaries and liver) which participates in the regulation of adipocyte development, inflammatory processes, and metabolic functions. Chemerin is gaining attention in gestation and it has been reported to be augmented in preeclampsia. This adipokine plays a physiological and protective role during early pregnancy; however, late complications in pregnancy may be observed when chemerin levels remain augmented. During pregnancy, maternal uterine artery (UA) blood flow is critical to maintaining the intrauterine environment, permitting normal placental function, and supporting fetal growth. Chemerin has been shown to contract many vascular beds, however, its role on the UA remains to be elucidated. This study tests the hypothesis that chemerin leads to increased contraction of UA contributing to the development of preeclampsia‐like symptoms and leading to gestational disorders. Pregnant (P) and non‐pregnant (NP) Sprague Dawley rats (200–250g) were injected daily (i.p.) with vehicle (saline) or chemerin (16 μg/rat;). On gestational day 20, or corresponding day for NP rats, animals were euthanized and placentas and fetuses weighted. UA was removed, cleaned and mounted in wire myograph. Concentration response‐curves to acetylcholine (ACh) and seretonin [5‐HT (1 nM to 100 μM); in the presence or absence of ERK1/2 inhibitor, PD98059] were performed in UA. Treatment with chemerin decreases the relaxation to ACh in both P [Emax 69.77 ± 4.90 vs. 95.50 ± 3.10] and NP [Emax 74.56 ± 4.52 vs. 96.04 ± 5.75] animals compared to respective controls. Increased sensitivity to 5‐HT was observed in the UAs of chemerin‐treated P [pD2 7.05 ± 0.05 vs. 6.60 ± 0.16] and NP [pD2 6.57 ± 0.07 vs. 6.14 ± 0.14] rats compared to vehicle rats, which was abolished by incubation with PD98059. Further, chemerin treatment on P animals resulted in increased placental weight [(g) 0.50 ± 0.016 vs. 0.43 ± 0.004] with no changes in fetal weight. We conclude that chemerin treatment impairs UA contractility and relaxation leading to placental disorder. These changes in UA function may be a predictive for elevate blood pressure in preeclampsia.Support or Funding InformationNIH 13604