Department of Chemical and Biological Physics, Weizmann Institute, 76100 Rehovot, Israel.
Department of Biological Regulation, Weizmann Institute, 76100 Rehovot, Israel.
Proc Natl Acad Sci U S A. 2018 Mar 6;115(10):E2429-E2436. doi: 10.1073/pnas.1715175115. Epub 2018 Feb 14.
Placental functions, including transport and metabolism, play essential roles in pregnancy. This study assesses such processes in vivo from a hyperpolarized MRI perspective. Hyperpolarized urea, bicarbonate, and pyruvate were administered to near-term pregnant rats, and all metabolites displayed distinctive behaviors. Little evidence of placental barrier crossing was observed for bicarbonate, at least within the timescales allowed by C relaxation. By contrast, urea was observed to cross the placental barrier, with signatures visible from certain fetal organs including the liver. This was further evidenced by the slower decay times observed for urea in placentas vis-à-vis other maternal compartments and validated by mass spectrometric analyses. A clear placental localization, as well as concurrent generation of hyperpolarized lactate, could also be detected for [1-C]pyruvate. These metabolites also exhibited longer lifetimes in the placentas than in maternal arteries, consistent with a metabolic activity occurring past the trophoblastic interface. When extended to a model involving the administration of a preeclampsia-causing chemical, hyperpolarized MR revealed changes in urea's transport, as well as decreases in placental glycolysis vs. the naïve animals. These distinct behaviors highlight the potential of hyperpolarized MR for the early, minimally invasive detection of aberrant placental metabolism.
胎盘的功能,包括运输和代谢,在妊娠中起着至关重要的作用。本研究从超极化 MRI 的角度评估了这些过程在体内的情况。将超极化尿素、碳酸氢盐和丙酮酸给予接近分娩的怀孕大鼠,所有代谢物都表现出独特的行为。至少在 C 弛豫允许的时间范围内,碳酸氢盐几乎没有证据表明穿过胎盘屏障。相比之下,尿素被观察到穿过胎盘屏障,其特征可见于某些胎儿器官,包括肝脏。这进一步通过在胎盘相对于其他母体隔室中观察到的尿素较慢的衰减时间得到证实,并通过质谱分析得到验证。[1-C]丙酮酸也可以清楚地定位在胎盘上,并同时产生超极化的乳酸。这些代谢物在胎盘内的寿命也比在母体动脉内长,这与在滋养层界面之后发生的代谢活动一致。当将其扩展到涉及给予导致子痫前期的化学物质的模型时,超极化 MR 揭示了尿素转运的变化,以及与未受影响的动物相比,胎盘糖酵解的减少。这些不同的行为突出了超极化 MR 用于早期、微创检测异常胎盘代谢的潜力。