Khankin Eliyahu V, Ko Nga Ling, Mandalà Maurizio, Karumanchi S Ananth, Osol George
Department of Medicine Beth Israel Deaconess Medical Center Harvard Medical School Boston MA USA.
Department of Obstetrics, Gynecology and Reproductive Sciences University of Vermont Larner College of Medicine Burlington VT USA.
FASEB Bioadv. 2021 Jul 5;3(9):702-708. doi: 10.1096/fba.2021-00019. eCollection 2021 Sep.
Outward remodeling of the maternal uterine circulation during pregnancy is essential for normal uteroplacental perfusion and pregnancy outcome. The physiological mechanism by which this process is regulated is unknown; we hypothesized that it involved the normalization of wall shear stress (WSS). Pregnant Sprague-Dawley rats underwent unilateral ligation of the main uterine artery and vein at the cervical end of the uterus on gestational day 10, thus restricting inflow/outflow of blood into that uterine horn to a single point at the ovarian end; the contralateral sham-operated side provided an internal control. This procedure alters uterine hemodynamics by increasing WSS, since the entire uterine horn is supplied by one rather than two vessels. Arterial diameter and blood flow velocity values were measured by intravital ultrasonographic pulse-wave Doppler on gestational day 20 and used to calculate WSS. Although both ovarian artery lumen diameter and blood velocity increased, WSS was similar in both horns. These data support the concept that increased WSS secondary to hemochorial placentation is the primary physiological stimulus for uterine vascular remodeling and that its normalization may be the primary mechanism that regulates the extent of arterial circumferential growth required to maintain placental perfusion. We further hypothesize that shallow spiral artery invasion, such as occurs in preeclampsia, limits the increase in upstream shear stress and results in attenuated remodeling and placental under-perfusion.
孕期母体子宫循环的向外重塑对于正常的子宫胎盘灌注和妊娠结局至关重要。该过程受调控的生理机制尚不清楚；我们推测其涉及壁面剪应力（WSS）的正常化。在妊娠第10天，对怀孕的Sprague-Dawley大鼠在子宫宫颈端进行单侧子宫主动脉和静脉结扎，从而将血液流入/流出该子宫角限制在卵巢端的单个点；对侧假手术侧作为内部对照。由于整个子宫角由一根而非两根血管供血，此操作通过增加WSS改变子宫血流动力学。在妊娠第20天，通过活体超声脉冲波多普勒测量动脉直径和血流速度值，并用于计算WSS。尽管卵巢动脉管腔直径和血流速度均增加，但两个子宫角的WSS相似。这些数据支持以下概念：血绒毛膜胎盘形成继发的WSS增加是子宫血管重塑的主要生理刺激因素，其正常化可能是调节维持胎盘灌注所需动脉周向生长程度的主要机制。我们进一步推测，如子痫前期中发生的浅螺旋动脉侵入会限制上游剪应力的增加，并导致重塑减弱和胎盘灌注不足。
