Behind the Curtain of Abnormal Placentation in Pre-Eclampsia: From Molecular Mechanisms to Histological Hallmarks

Abstract

Successful human pregnancy needs several highly controlled steps to guarantee an oocyte's fertilization, the embryo's pre-implantation development, and its subsequent implantation into the uterine wall. The subsequent placenta development ensures adequate fetal nutrition and oxygenation, with the trophoblast being the first cell lineage to differentiate during this process. The placenta sustains the growth of the fetus by providing it with oxygen and nutrients and removing waste products. It is not surprising that issues with the early development of the placenta can lead to common pregnancy disorders, such as recurrent miscarriage, fetal growth restriction, pre-eclampsia, and stillbirth. Understanding the normal development of the human placenta is essential for recognizing and contextualizing any pathological aberrations that may occur. The effects of these issues may not become apparent until later in pregnancy, during the mid or advanced stages. This review discusses the process of the embryo implantation phase, the molecular mechanisms involved, and the abnormalities in those mechanisms that are thought to contribute to the development of pre-eclampsia. The review also covers the histological hallmarks of pre-eclampsia as found during the examination of placental tissue from pre-eclampsia patients.

Keywords: embryology; histological hallmarks; placentation; pre-eclampsia.

Figure 1

Schematic representation of embryo implantation. (A) Implantation at day 5–6 days POC, the blastocyst attaches to the endometrium via its embryonic pole; (B) at about 7–10 days POC, the blastocyst penetrates deeply in the endometrium. Two layers can be recognized: an inner layer (cytotrophoblast) and an outer syncytial layer (the syncytiotrophoblast); (C) the syncytiotrophoblast expands into the endometrial decidualized mucosa; (D) lacunae appears in the syncytiotrophoblast cellular mass; a fibrin plug covers the implantation site; (E) the destructive activity of the syncytiotrophoblast reaches the endometrial vessels; maternal blood flows into the lacunae; (F) the syncytiotrophoblast surrounds the maternal capillaries, enlarges its network of lacunae, and establishes the placenta’s circulatory system.

Figure 2

(A) Acute atherosis: fibrinoid necrosis (arrowhead) of the spiral arterial wall. Lipid-laden macrophages (arrow) are enclosed in the eosinophilic amorphous material, which surrounds the vessel (H&E, original magnification 50×); (B) distal villous hypoplasia; terminal villi have a “pencil-like” appearance (arrows) (H&E, original magnification 100×); (C) Tenney–Parker change (syncytial knots—arrows) (H&E, original magnification 200×); (D) deciduo-chorial necrosis (arrow) in the chorial membrane (H&E, original magnification 100×); (E) decidual multinucleated giant-cells (extravillous trophoblast—arrows) (H&E, original magnification 100×).