A review of Robertson, Brosens and Pijnenborgs’ early work showed essentially similar or identical observations to the decidual vasculopathy in the current pathology guideline, with the exception that those findings in their original descriptions were in the inner layer of the myometrium, or the myometrial/decidual junction [
12,
13,
60,
63]. These investigators proposed the term “physiological changes” in normal pregnancy and the theory of “failure of invasion” to depict the lack of trophoblastic remnants within the arterial walls and within the inner layers of myometrium, and defined the lack of trophoblastic invasion of the vascular wall as the cardinal feature of the preeclampsia or hypertensive disorders of pregnancy, as well as of other obstetric disorders [
64]. The morphologic changes of the spiral artery in the decidua in preeclampsia have been described by many other early investigators, and it seems that all the investigators agree that these vascular changes are associated with preeclampsia [
5,
65]. The issue appears to be the interpretation of the same, or a similar, morphologic vascular transformation in a spatiotemporal manner among the early investigators. Hertig described these vascular changes in preeclampsia as “acute degenerative arteriolitis”, with the “collection of foamy fat laden mononuclear leukocytes or phagocytes” [
5]. These vascular changes observed by Hertig appeared to be within the decidua, and not in the myometrium, and these morphologic changes were considered the basis of pathologic findings associated with the preeclampsia and hypertensive disorders of pregnancy following placental examination. There is a large body of literature that followed the initial description of Hertig in the pathology texts [
1]. The vascular changes within the myometrium, described early by Robertson, Brosens and Pijnenborg, can be classified today as acute atherosis and mural arterial hypertrophy/hyperplasia, but these changes were found in the myometrium and not in the decidua, raising the question of their equivalency to decidual vasculopathy today [
2]. Some of the vessels in Brosens and Pijnenborgs’ work showed various degrees of arterial restoration, with early endothelial and smooth muscle regeneration, and these regenerative changes were described as a “cushion” with or without mural thrombosis, which was found to be mutually exclusive with endovascular trophoblasts or trophoblasts within the fibrinoid vascular walls [
12,
13]. The concept of vascular restoration/regeneration after “physiologic changes”, or decidual vasculopathy, is only appropriate when the vascular changes are considered in a dynamic and spatiotemporal manner. There was only a brief mention of repair change in the work of Brosens and Pijnenborg, in either decidua or myometrium, without data or systemic study of “vascular regeneration/restoration”. Much of the placental bed biopsies revealed results similar to those described in the myometrium, as these biopsies were taken after the placentas were delivered [
66]. The theory of “failure to invade” acknowledges the presence of the vascular changes, such as acute atherosis and fibrinoid medial necrosis, in the location of decidua as “pathological”, but defines the changes within the myometrium as “physiological”. It is possible that the “physiologic changes” described by these investigators were located in the central portion of the placenta, and the asynchronous spiral artery remodeling associated with the placental lateral growth pattern is described below. The “physiologic changes” within the myometrium could be an extension and continuation of the same morphologic features of decidual vasculopathy into the myometrial segment of the spiral artery, and these “physiologic changes” could represent various degrees of vascular restoration/regeneration after the initial vascular transformation in early pregnancy. From an anatomical viewpoint, the decidual segment of the spiral artery will undergo vascular transformation first during early pregnancy, extending into the myometrial segment of the spiral artery, whereas the myometrial segment of the spiral artery will recover (regenerate/restore) first, if the endothelial cells within the proximal artery serve as progenitor cells for both endothelial cells and smooth muscle cells in the vascular lumen. Many angiocrine factors have been described for tissue-specific endothelium in vascular regeneration, and these angiocrine factors are likely the keys to understanding the role of endothelium as progenitor cells during and after pregnancy [
34,
35,
36,
67]. We examined one hysterectomy specimen, with the placenta in the central region, with regards to decidua and the myometrial segments of the spiral artery. The presence of CD56-positive endovascular and intramural trophoblasts within the decidua supports the view of decidual vasculopathy, and these vascular changes were connected to the myometrial segments of the spiral artery without CD56-positive endovascular or intramural trophoblasts, but with WT1-positive endothelium and SMYOHC-positive smooth muscle cells [
29,
56]. The key morphologic features of “failure to invade” in the early work are those of smooth muscle mural hypertrophy/hyperplasia, as defined in the current placental pathology guideline [
2]. These particular morphologic features were shown to be more associated with essential hypertension in the early work [
13,
68]. It is important to note again that current guidelines on placental examination concern placentas after delivery, whereas the “failure to invade” theory was based on the vascular changes within the myometrium. Our own experience of the placentas after delivery is that mural hypertrophy/hyperplasia is commonly seen in small caliber arteries, and more commonly seen in the decidua capsularis (vera). Mural hypertrophy/hyperplasia alone, similar to classic type vasculopathy alone, does not significantly affect the placental growth and weight [
4]. However, mural hypertrophy/hyperplasia associated with classic vasculopathy in the same placenta significantly affects the placental weight and growth at the late gestation stage [
4]. As suggested previously, mural hypertrophy/hyperplasia appears to be affected by endocrine or circulating factors, without direct interaction with trophoblasts, and the presence of the mixed type of vasculopathy (mural hypertrophy/hyperplasia and classic type vasculopathy) reflects abnormal interactions both locally, between the endothelium and trophoblasts, and globally, within the maternal circulation [
6]. While mural hypertrophy/hyperplasia is a part of the disease process in late gestation, as a cardinal feature of “failure to invade” theory, mural hypertrophy/hyperplasia represents a limited aspect of the pathogenesis of the preeclampsia or hypertensive disorders of pregnancy, as well as other pregnancy-related complications.