What is the role of trophoblast (trophoblastic) invasion in pregnancy?

From the Guidelines

Trophoblast invasion during pregnancy is a critical process that must be carefully managed to prevent complications such as placenta accreta, which can lead to severe maternal morbidity and mortality, and therefore, requires accurate antenatal diagnosis and planned delivery at an experienced center, as recommended by the American Congress of Obstetricians and Gynecologists (ACOG) and the International Federation of Obstetrics and Gynecology (FIGO) 1. The process of trophoblast invasion begins shortly after implantation, when cytotrophoblast cells differentiate into extravillous trophoblasts that migrate into the decidua and maternal spiral arteries, with the primary purpose of remodeling these arteries to increase blood flow to the placenta and fetus.

Key Factors in Trophoblast Invasion

• The balance of trophoblast invasion is essential for normal placental development and a healthy pregnancy outcome, with inadequate invasion associated with complications such as preeclampsia and placental abruption, and excessive invasion leading to conditions like placenta accreta 1.
• The risk of placenta accreta spectrum disorder (PASD) has increased over the past decades, with a current incidence of approximately 1 in 500 deliveries, and is associated with prior cesarean delivery, placenta previa, and other factors such as advanced maternal age and uterine anomalies 1.
• Accurate antenatal diagnosis of PASD is crucial to plan for an appropriate delivery strategy, with the American Congress of Obstetricians and Gynecologists (ACOG) and FIGO recommending planned cesarean delivery with or without hysterectomy, depending on the suspected severity of PASD, around 34 to 38 weeks gestation 1.

Management of Trophoblast Invasion

• The management of trophoblast invasion and PASD requires a multidisciplinary approach, with close follow-up by experienced centers and a contingency plan for emergent delivery, as well as radiologic and clinical data to formulate an appropriate delivery strategy 1.
• The timing of delivery is planned carefully on a case-by-case basis to achieve optimal fetal maturity and avoid the chance of spontaneous labor, with a planned delivery preferred to reduce maternal morbidity and mortality 1.
• Planned cesarean delivery with or without hysterectomy, depending on the suspected severity of PASD, around 34 to 38 weeks gestation, is the recommended management strategy for trophoblast invasion and PASD, as it can help reduce maternal morbidity and mortality, and improve outcomes for both the mother and the fetus 1.

From the Research

Trophoblast Invasion in Pregnancy

• Trophoblast invasion is a crucial component of the establishment of pregnancy, where extravillous trophoblast invades the uterine wall 2.
• This process is tightly regulated and involves the transformation of maternal spiral arteries, tolerance of hypoxia, proliferation, and differentiation of trophoblast cells 2.
• Successful invasion is essential for the survival of the fetus, as it secures an adequate supply of oxygen and nutrients 2.

Mechanisms of Trophoblast Invasion

• The invasion of uterine glands by endoglandular trophoblast enables histiotrophic nutrition of the embryo prior to perfusion of the placenta with maternal blood 3.
• Endovenous trophoblasts invade uterine veins to guarantee the drainage of fluids from the placenta back into the maternal circulation throughout pregnancy 3.
• Endolymphatic trophoblasts invade lymph vessels of the uterus, and endoarterial trophoblasts invade spiral arteries, enabling hemotrophic nutrition of the fetus starting with the second trimester of pregnancy 3.

Abnormal Trophoblast Invasion

• Defective trophoblast invasion underlies fetal growth restriction and preeclampsia-like symptoms in the stroke-prone spontaneously hypertensive rat 4.
• Abnormal placentation with defective remodeling of the spiral arteries precedes the onset of the maternal syndrome in preeclampsia 4.
• Chronic hypertension interferes with early events during the placentation process, leading to impaired remodeling of the spiral arteries and abnormal trophoblast invasion 4.

Regulation of Trophoblast Invasion

• The master regulatory transcription factor controlling the epithelial-mesenchymal transition (EMT) in trophoblast invasion appears to be ZEB2 (zinc finger E-box binding protein 2) 5.
• Overexpression of ZEB2 in trophoblast cell lines leads to increased invasiveness and up-regulation of EMT-associated genes 5.
• The identification of the differentiation mechanism will enable the identification of factors controlling invasion and those aberrant processes that generate abnormal invasion seen in pathologies such as abnormally invasive placenta (AIP) and preeclampsia 5.