Elsevier

Placenta

Volume 27, Issues 9–10, September–October 2006, Pages 939-958
Placenta

The Uterine Spiral Arteries In Human Pregnancy: Facts and Controversies

https://doi.org/10.1016/j.placenta.2005.12.006Get rights and content

Abstract

Uterine spiral arteries play a vital role in supplying nutrients to the placenta and fetus, and for this purpose they are remodelled into highly dilated vessels by the action of invading trophoblast (physiological change). Knowledge of the mechanisms of these changes is relevant for a better understanding of pre-eclampsia and other pregnancy complications which show incomplete spiral artery remodelling. Controversies still abound concerning different steps in these physiological changes, and several of these disagreements are highlighted in this review, thereby suggesting directions for further research. First, a better definition of the degree of decidua- versus trophoblast-associated remodelling may help to devise a more adequate terminology. Other contestable issues are the vascular plugging and its relation with oxygen, trophoblast invasion from the outside or the inside of the vessels (intravasation versus extravasation), the impact of haemodynamics on endovascular migration, the replacement of arterial components by trophoblast, maternal tissue repair mechanisms and the role of uterine natural killer (NK) cells. Several of these features may be disturbed in complicated pregnancies, including the early decidua-associated vascular remodelling, vascular plugging and haemodynamics. The hyperinflammatory condition of pre-eclampsia may be responsible for vasculopathies such as acute atherosis, although the overall impact of such lesions on placental function is far from clear. Several features of the human placental bed are mirrored by processes in other species with haemochorial placentation, and studying such models may help to illuminate poorly understood aspects of human placentation.

Introduction

The interrelationship between maternal and fetal circulations enabling physiological exchange within the placenta is still not fully understood. Probably the most significant breakthrough was achieved in the 18th century when William and John Hunter demonstrated by injection experiments that maternal and fetal vascular structures remain separate, thus refuting the previously held opinion of a continuous mother-to-fetus circulation. This might have been a chance observation, since injecting blood vessels with coloured wax was becoming a routine procedure for anatomical demonstrations at that time. Most probably it was the younger brother John, who actually did the dissections, who quickly grasped the physiological implications of this observation, which in later years led to a quarrel concerning priority [1], [2]. Nevertheless, it was William who illustrated for the first time spiral arteries in his famous “Anatomia uteri humani gravidi tabulis illustrata – The anatomy of the human gravid uterus exhibited in figures” (1774) [3], in a series of superb engravings based on careful dissections of several pregnant uteri. The spiral arteries were then described as “arteriae convolutae/convoluted arteries” which are “passing between the womb and placenta”. These vessels were most clearly visible in drawings of the inside of the uterus after separation of the placenta, “which we broke through in separating these two parts”. This short passage reveals their ignorance about the factual arrangement of maternal blood supply to the placenta. In spite of the ingenuity of the Hunter brothers, they could not have envisioned at that time how the uteroplacental circulation is established by the action of invading cells from the placenta. Since this review deals a lot with placental–uterine interactions, it may be relevant that it was also William Hunter who introduced the term “decidua” for the thickened inner lining of the pregnant uterus which is discarded at parturition. The term is etymologically significant since the Latin word “decidere” means “to fall off”, which also applies to the expulsion of the decidualizing uterine mucosa at menstruation.

After these pioneering observations it took more than a century to clarify the detailed anatomy of the uterine vasculature [4], [5], [6]. The matter is basically settled now, although some confusion arose concerning terminology, i.e. whether the arteries in the inner myometrium should be considered as spiral [7] or radial arteries [8] (Fig. 1). Part of the argument was due to a disagreement about the level where the basal arteries are branching off in the decidua or in the myometrium, as this point is considered to form the demarcation line between radial and spiral arteries. Meanwhile observations on placental bed biopsies have confirmed the deep myometrial origin of basal arteries, which nourish both the inner myometrium and basal endometrium. Therefore the designation of the inner myometrial arteries as spiral arteries has subsequently been followed. A precise terminology – although it may look like a rather insignificant issue – is important regarding the depth over which pregnancy-associated changes in spiral arteries are reported to occur.

Studies on the endometrial spiral arteries of the non-pregnant uterus indicated the remarkable sensitivity of these vessels to stimuli by hormones or growth factors, while the basal arteries are thought to be more stable non-hormone responsive structures [4], [8], [9]. The convoluted course of the spiral arteries obviously results from arterial growth exceeding the increase in endometrial thickness during the cycle and during pregnancy. There can be no doubt that this spiral shape has haemodynamical repercussions. John Hunter already noted that “The intention of these spiral turns would appear to be that of diminishing the force of the circulation as it approaches the spongy substance of the placenta  where quick motion of the blood is not wanted” (quoted by Ramsey [6]). Their peculiar shape would not only lead to a progressive decrease in blood pressure along their length, but would also dampen the pulse, which is important for maintaining a steady blood flow to the intervillous space of the placenta. Ramsey found that the coiling of the spiral arteries still increased in early pregnancy, but that uncoiling started around midpregnancy [6], [10]. The reserve length of the convoluted vessels obviously allows easy stretching during pregnancy-associated uterine growth.

Reynolds [4] made the interesting point that coiled or spiral arteries are not seen in the endometria of most non-pregnant animals, and therefore he speculated that their peculiar shape in primates may be related to menstruation. In fact, increased coiling of endometrial arteries is related to decidualization of the endometrium which in primates is started off spontaneously during the luteal phase of each cycle. In non-menstruating animals such as rats, mice and hamsters, spiral outgrowth of uteroplacental arteries definitely occurs during pregnancy and is also associated with the decidualization process, which in these animals does not occur spontaneously during their estrous cycle, but is induced by blastocyst implantation [11].

Section snippets

Basic histological observations on spiral arteries during pregnancy: a historical overview

The earliest histological observations on uterine spiral arteries in human pregnancy were reported by German investigators in the last third of the 19th century. This early research was summarized and extensively discussed by Grosser, and his monograph should be consulted for detailed references [12]. He quoted Friedländer (1870) as the first to have described endovascular cells in maternal arteries at midpregnancy, without making any statement as to their possible origin. Most investigators

Decidualization of spiral arteries and trophoblast-independent changes

The aforementioned concept of “decidual changes” in spiral arteries as a necessary prelude to trophoblast invasion, attractive as it might be, still needs further substantiation. In how far early vascular decidualization is a conditio sine qua non for the later trophoblast-associated vascular remodelling is still not known.

Several years after the first vascular decidualization studies [18], [29], [31], the idea of trophoblast-independent changes of spiral arteries was revived by Craven et al.

Defects in spiral artery remodelling in pregnancy complications

As mentioned before, it was the demonstration of impaired maternal placental perfusion in hypertensive pregnancies [23] that triggered the search for vasculopathies in the placental bed as possible causes for placental insufficiency and fetal growth restriction [24]. In 1972, Brosens et al. [25] reported for the first time that, in contrast to normal pregnancies, spiral arteries with “normal” histological arterial features, i.e. without “physiological change”, could be easily found in the

Epilogue – reconstitution of the arterial wall after parturition

Because of the drastic changes in spiral artery structure during pregnancy, one might wonder how the original vessel wall is restored after parturition. It is generally thought that trophoblast persists in the uterine wall for a week to 10 days postpartum [151], but in order to have a complete picture of the vascular reconstitution, a day-to-day follow-up study of the former placental bed site would be needed. Unfortunately, the only materials available are curettage and hysterectomy specimens

Conclusion

From this overview it will be clear that there are still a lot of controversies and uncertainties about the exact pathways and mechanisms of spiral artery remodelling, as well as the specific effects of endovascular and/or interstitial trophoblast. As a result, plenty of “placental bed stories” have been told by different investigators, including ourselves. Although a lot of experimental research has already been performed on mechanisms of trophoblast invasion, most findings relate to invasive

Acknowledgement

The authors wish to thank Tom Pijnenborg for his advice and practical help with the illustrations.

References (159)

  • W. Moll

    Absence of intervillous blood flow in the first trimester of human pregnancy

    Placenta

    (1995)
  • A.M. Carter

    When is the maternal placental circulation established in man?

    Placenta

    (1997)
  • J.W. Meekins et al.

    Histological study of decidual spiral arteries and the presence of maternal erythrocytes in the intervillous space during the first trimester of normal human pregnancy

    Placenta

    (1997)
  • E. Jauniaux et al.

    Onset of maternal arterial blood flow and placental oxidative stress

    Am J Pathol

    (2000)
  • G.J. Burton et al.

    Maternal arterial connections to the placental intervillous space during the first trimester of human pregnancy: the Boyd collection revisited

    Am J Obstet Gynecol

    (1999)
  • E. Jauniaux et al.

    Trophoblastic oxidative stress in relation to temporal and regional differences in maternal placental blood flow in normal and abnormal early pregnancies

    Am J Pathol

    (2003)
  • R. Matijevic et al.

    Spiral artery blood flow in the central and peripheral areas of the placental bed in the second trimester

    Obstet Gynecol

    (1995)
  • I. Caniggia et al.

    Oxygen and placental development during the first trimester: implications for the pathophysiology of pre-eclampsia

    Trophoblast Res

    (2000)
  • J.N. Bulmer et al.

    Expression of the proliferation markers Ki67 and transferrin receptor by human trophoblast populations

    J Reprod Immun

    (1988)
  • S.L. Adamson et al.

    Interactions between trophoblast cells and the maternal and fetal circulation in the mouse placenta

    Dev Biol

    (2002)
  • S. Esadeg et al.

    Alpha-2 macroglobulin controls trophoblast positioning in mouse implantation sites

    Placenta

    (2003)
  • T.D. Burrows et al.

    Expression of adhesion molecules by endovascular trophoblast and decidual endothelial cells: implications for vascular invasion during implantation

    Placenta

    (1994)
  • R. Pijnenborg

    Uterine haemodynamics as a possible driving force for endovascular trophoblast migration in the placental bed

    Med Hypotheses

    (2000)
  • A. Soghomonians et al.

    Effect of shear stress on migration and integrin expression in macaque trophoblast cells

    Biochim Biophys Acta

    (2002)
  • D. Martin et al.

    Expression of endothelial nitric oxide synthase by extravillous trophoblast cells in the human placenta

    Placenta

    (2000)
  • W.B. Robertson et al.

    Uteroplacental vascular pathology

    Eur J Obstet Gynecol Reprod Biol

    (1975)
  • S.C. Robson et al.

    Punch biopsy of the human placental bed

    Am J Obstet Gynecol

    (2002)
  • F. Lyall

    The human placental bed revisited

    Placenta

    (2002)
  • I. Thaler et al.

    Changes in uterine blood flow during human pregnancy

    Am J Obstet Gynecol

    (1990)
  • J.D. Aplin

    Expression of integrin a6b4 in human trophoblast and its loss from extravillous cells

    Placenta

    (1993)
  • P.K. Lala et al.

    Growth factors, proteases and protease inhibitors in the maternal–fetal dialogue

    Placenta

    (1996)
  • R. Pijnenborg et al.

    The distribution of fibronectin in the placental bed in normotensive and hypertensive human pregnancies

    Trophoblast Res

    (1992)
  • F. Lyall et al.

    Human trophoblast invasion and spiral artery transformation. The role of PECAM-1 in normal pregnancy, preeclampsia, and fetal growth restriction

    Am J Pathol

    (2001)
  • R. Bulla et al.

    VE-cadherin is a critical molecule for trophoblast–endothelial cell interaction in decidual spiral arteries

    Exp Cell Res

    (2005)
  • P.M. Dunn

    Dr William Hunter (1718–83) and the gravid uterus

    Arch Dis Child Fetal Neonatal Ed

    (1999)
  • W. Moore

    The knife man: the extraordinary life and times of John Hunter, father of modern surgery

    (2005)
  • W. Hunter

    Anatomia uteri humani gravidi tabulis illustrata – the anatomy of the human gravid uterus exhibited in figures

    (1980)
  • S.R.M. Reynolds

    Physiology of the uterus

    (1949)
  • N. Lundgren

    Studies on the vasculature of the corpus of the human uterus

    Acta Obstet Gynecol Scand

    (1957)
  • E.M. Ramsey

    The story of the spiral arteries

    J Reprod Med

    (1981)
  • I. Brosens et al.

    The physiological response of the vessels of the placental bed to normal pregnancy

    J Pathol Bacteriol

    (1967)
  • E.M. Ramsey et al.

    Placental vasculature and circulation

    (1980)
  • J.D. Boyd et al.

    The human placenta

    (1970)
  • E.M. Ramsey et al.

    Comparison of uteroplacental vasculature and circulation in the rhesus monkey and man

    Contrib Embryol Carnegie Inst Wash

    (1966)
  • R. Pijnenborg et al.

    Trophoblast invasion and the establishment of haemochorial placentation in man and laboratory animals

    Placenta

    (1981)
  • O. Grosser

    Frühentwicklung, Eihautbildung und Placentation des Menschen und der Säugetiere

    (1927)
  • J.D. Boyd et al.

    Cells in the spiral arteries of the pregnant uterus

    J Anat

    (1956)
  • J.D. Boyd et al.

    Development and structure of the human placenta from the end of the 3rd month of gestation

    J Obstet Gynaecol Br Commonw

    (1967)
  • W.J. Hamilton et al.

    Development of the human placenta in the first three months of gestation

    J Anat

    (1960)
  • W.J. Hamilton et al.

    Trophoblast in human utero-placental arteries

    Nature

    (1966)
  • Cited by (912)

    • Spiral, uterine artery doppler and placental ultrasound in relation to preeclampsia

      2024, Best Practice and Research: Clinical Obstetrics and Gynaecology
    View all citing articles on Scopus
    View full text