Preeclampsia (PE) is a hypertensive disorder of pregnancy with an incompletely understood etiology affecting approximately 10% of pregnancies worldwide. Obesity is a risk factor among women that develop PE and is mirrored in the blood pressure high subline 5 (BPH/5) mouse. Before pregnancy, BPH/5 adult females are hyperphagic, obese and dyslipidemic with increased reproductive white adipose tissue (rWAT) that expands throughout pregnancy, along with other PE-like symptoms. Pregnant BPH/5 females develop poor placentation with decreased trophoblast invasion and inadequately remodeled decidual vessels, a recognized feature of PE. Kisspeptins (KP), a family of small peptides encoded by the Kiss1 gene, are important regulators of cellular migration and proliferation. They have been shown to inhibit the migration and invasion of trophoblast cells in humans and rodents and may be involved in abnormal placentation observed in PE. Interestingly, Kiss1/Kiss1r are also expressed in the adipose tissue with a potential role in metabolism regulation, including inhibition of adipogenesis and lipolysis induction. When fed a normal diet, adult female kiss1r-knockout mice have reduced energy expenditure, increased adiposity and body weight (BW) than wild-type littermates. Hence, we aimed to characterize Kiss1/Kiss1r mRNA expressionin BPH/5 rWAT and the uteroplacental interface at the peak of decidualization. We hypothesized that at embryonic day (e) 7.5, Kiss1/Kiss1r will be higher in BPH/5 implantation sites, but lower in the rWAT, when compared to control C57. Furthermore, we hypothesized that feeding BPH/5 dams a 25% calorie restriction (CR) diet, beginning at conception (e0.5), would normalize the Kiss1/Kiss1r in e7.5 implantation sites and rWAT. To test our hypothesis, implantation sites and rWAT were collected at e7.5 from adult BPH/5 and C57 fed ad libitum, and age-matched e7.5 BPH/5 females after 25% CR from e0.5 to e7.5 (n = 5-9/group). Kiss1/Kiss1r were measured using RT-PCR and comparisons were performed using independent samples t-test (SPSS) with significance set at 5%. BPH/5 e7.5 implantation sites had 2-fold higher Kiss1/Kiss1r when compared to C57 (p < 0.05). In the rWAT, Kiss1 was approximately five-fold lower in BPH/5 vs. C57 (p < 0.05). When considering Kiss1r, however, the expression was 1.5-fold higher in BPH/5 vs. C57 (p < 0.05). When comparing ad libitum BPH/5 and 25% CR BPH/5 females at e7.5, there was no difference in the rWAT Kiss1/Kiss1r (p > 0.05). Therefore, upregulation of Kiss1/Kiss1r at the utero-placental interface during the peak of decidualization, along with increased Kiss1r in the rWAT characterizes the BPH/5 model of PE. Concurrently, the Kiss1 levels are lower in the BPH/5 rWAT at e7.5 and may be associated with the increased adiposity of these mice previously shown throughout gestation. Even though 7 days of 25% CR has been previously shown to decrease the body weight of pregnant BPH/5 females, it did not alter the expression levels of Kiss1/Kiss1r in the rWAT at e7.5. Further studies are necessary to investigate KP expression in the adipose tissue of CR BPH/5 females at later timepoints of gestation and their role in placental development in PE.
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