Placenta 97 (2020) 36–41 Available online 18 June 2020 0143-4004/© 2020 Published by Elsevier Ltd. Acute atherosis and diffuse lipid infiltration of the placental bed: A review of historical lipid studies Ivo Brosens a, * , Jan J. Brosens b , Joanne Muter b , Giuseppe Benagiano c a Faculty of Medicine, KU Leuven, Leuven, Belgium b Tommy’s National Centre for Miscarriage Research, University Hospitals Coventry & Warwickshire, Coventry, CV2 2DX, UK c Department of Maternal and Child Health, Gynaecology and Urology, Sapienza, University of Rome, Rome, Italy A R T I C L E INFO Keywords: Acute atherosis Atherosclerosis Diffuse lipid infiltration Hypertension Preeclampsia Decidua Placental bed ABSTRACT Based on a variety of tissue samples, including Caesarean hysterectomy specimens with the placenta in situ, a detailed map of uteroplacental vascular lesions was established in over a century of research. One such lesion is acute atherosis of unremodelled basal and uteroplacental arteries, defined by the presence of fibrinoid necrosis, subendothelial macrophage foam cells, and perivascular lymphocytic infiltration. Two studies conducted over 50 years ago used Oil Red O staining of frozen tissue sections to visualise lipid infiltration of placental bed vessels and document the presence of lipid-laden foam cells in acute atherosis. These studies also demonstrated that significant amounts of intracellular and extracellular lipids can accumulate in the decidua basalis, often extending into the superficial layer of the myometrium. This phenomenon, termed diffuse lipid infiltration (DLI), was found not only to be prevalent in hypertensive and preeclamptic pregnancies but also associated with postterm pregnancies. Despite being a potential pathognomonic sign of placental malfunction, DLI has been neglected in the context placental bed pathophysiology. To renew interest in this putative pathological feature, and stimulate mechanistic investigations, we review here the original and, to our knowledge, only lipid studies on frozen placental bed tissue sections. 1. Introduction We recently reviewed how our understanding of the complex fea- tures of the interface between the mother and the fetus - the so-called ‘placental bed’ [1] - was shaped over more than a century of in- vestigations [2,3]. This led to an in-depth evaluation of the relationship between defective remodelling of the uteroplacental arteries in the myometrial portion of the placental bed and the Great Obstetrical Syn- dromes, encompassing preeclampsia, spontaneous preterm labour, fetal growth restriction, preterm premature rupture of membranes, sponta- neous mid-trimester miscarriage, and placental abruption [4,5]. Acquisition and analysis of placental bed biopsies that include myo- metrium can be technically challenging [6]. Hence, some recent studies have focussed on lesions in un-remodelled arteries in the decidual portion of the basal plate of the placenta [7,8]. Most uteroplacental spiral arteries in the basal plate are remodelled, perhaps with the exception of some vessels at the periphery of the placenta. Apart from spiral arteries that supply the intervillous space, the decidua also har- bours basal arteries, which are small branches of the radial or spiral arteries. These basal arteries terminate in the decidua basalis but do not open into the intervillous space [9]. Acute atherosis of basal and spiral arteries not remodelled by trophoblast is a conspicuous vasculopathy in pregnancy [10]. It is also a contentious lesion and its incidence and pathological significance has been the subject of debate for many decades [7,10–12]. The first description of acute atherosis was probably reported by Hertig in 1945 in women with preeclampsia, which at the time was called ‘hypertensive albuminuric toxemia’ [13]. In 1950, two studies on preeclamptic women were published detailing the salient pathological features of acute atherosis, including accumulation of macrophages filled with lipids (i.e. foam cells), thickening of the tunica intima (hereafter referred to as ‘intima’), and fibrinoid necrosis of the tunica media [14,15]. Acute vessel necrosis associated with intramural foam cell infiltrates was described by Lendrum et al. as a form of ‘plasmatic vasculosis’ [16]. The pathogenesis of acute atherosis remains incompletely under- stood [12,17]. However, it is reasonable to assume that it is similar to atherogenesis in other organs. Recently, Nakagawa and Nakashima re- ported a detailed description of the sequence of morphological changes * Corresponding author. Faculty of Medicine, KU Leuven, Oud-Heverleestraat 83, 3001, Leuven, Belgium. E-mail address: ivo.brosens@med.kuleuven.be (I. Brosens). Contents lists available at ScienceDirect Placenta journal homepage: http://www.elsevier.com/locate/placenta https://doi.org/10.1016/j.placenta.2020.06.012 Received 25 October 2019; Received in revised form 1 June 2020; Accepted 15 June 2020