Identification of uterine pacemaker regions at the myometrial–placental interface in the rat

Abstract

Key Points Coordinated contraction of the uterine smooth muscle is essential to parturition.Histologically and physiologically defined pacemaker structures have not been identified in uterine smooth muscle.Here we report combined electrophysiological and histological evidence of zones associated with pacemaker activity in the rat myometrium.Our method relies crucially on the integration of histological and electrophysiological data in an in silico three‐dimensional reconstruction of the rat myometrium at 10 μm resolution.We find that myometrial/placental pacemaking zones are closely related with placental sites and the area of disruptive myometrial remodelling surrounding such sites.If analogues of the myometrial/placental pacemaking zone are present in the human, defining their histology and physiology will be important steps towards treatment of pre‐term birth, pre‐eclampsia, and postpartum haemorrhage. AbstractCoordinated uterine contractions are essential for delivering viable offspring in mammals. In contrast to other visceral smooth muscles, it is not known where excitation within the uterus is initiated, and no defined pacemaking region has hitherto been identified. Using multi‐electrode array recordings and high‐resolution computational reconstruction of the three‐dimensional micro‐structure of late pregnant rat uterus, we demonstrate that electrical potentials are initiated in distinct structures within the placental bed of individual implantation sites. These previously unidentified structures represent modified smooth muscle bundles that are derived from bridges between the longitudinal and circular layers. Coordinated implantation and encapsulation by invading trophoblast give rise to isolated placental/myometrial interface bundles that directly connect to the overlying longitudinal smooth muscle layer. Taken together, these observations imply that the anatomical structure of the uterus, combined with site‐specific implantation, gives rise to emergent patterns of electrical activity that drive effective contractility during parturition.

The haemodynamics of the human placenta in utero

“…This phenomenon may relate to previous reports that anchoring villi (connecting the chorionic plate to the uterine wall) are contractile, because such contractility would assist in maintaining the shape of the placenta as the wall contracts [7]. It may also be related to the myometrial-placental pacemaker zone that has recently been identified in rats [49]. It is likely that such utero-placental contractions may have previously been identified as Braxton Hicks contractions involving the whole uterine wall (S3C Fig), or localized uterine contractions on ultrasound [50] and MRI [50,51], which have been associated with transient reductions in both uterine blood flow [52] and placental oxygenation [37].…”

“…We also need to understand what triggers the contractions: is it a reduction in oxygenation or an increase in pressure within the placenta? Are the contractions initiated in the myometrium of the placental bed [49] or by the anchoring villi [7]? The rate of detection of contractions was higher in PEs than in HCs, but longer sampling in more participants is required to be confident of any difference.…”

The haemodynamics of the human placenta in utero

“…This phenomenon may relate to previous reports that anchoring villi (connecting the chorionic plate to the uterine wall) are contractile, since such contractility would assist in maintaining the shape of the placenta as the wall contracts [7]. It may also be related to the myometrial-placental pacemaker zone that has recently been identified in rats [49]. It is likely that such uteroplacental contractions may have previously been identified as Braxton Hicks contractions involving the whole uterine wall (Fig.…”

“…We also need to understand what triggers the contractions: is it a reduction in oxygenation, or an increase in pressure within the placenta? Are the contractions initiated in the myometrium of the placental bed [49] or by the anchoring villi [7]? The rate of detection of contractions was higher in PEs than HCs, but longer sampling in more subjects is required to be confident of any difference.…”

Setting the pace for labour

“…Maximal survival of all pups would be facilitated if the placentae of pups closest to the cervix became detached from the uterine wall earlier in the labour process, while those closer to the oviduct remained firmly attached to the uterine wall. It is unclear from the study of Lutton et al , whether and to what extent this might have occurred. In other words, a sophisticated contraction gradient along the uterus might be required.…”