What is the process of placenta formation?

Formation of the Human Placenta

The placenta forms through a precisely coordinated process beginning at implantation, where trophoblast cells differentiate along two distinct pathways—villous and extravillous—to create the maternal-fetal interface that supports fetal development throughout pregnancy. 1, 2

Initial Implantation and Early Development

After the blastocyst implants into the uterine wall, trophoblast cells undergo rapid proliferation and differentiation to establish the placental foundation 3. This process is tightly regulated by oxygen tension, transcription factors, hormones, growth factors, and signaling molecules 1.

The Two Pathways of Trophoblast Differentiation

Villous Trophoblast Pathway

• Cytotrophoblast cells fuse to form the multinucleated syncytiotrophoblast, which covers the entire surface of the chorionic villi and serves as the primary interface for maternal-fetal exchange 2, 4
• The syncytiotrophoblast forms the outer epithelial layer of chorionic villi, where it is separated from maternal blood by only three to four cell layers (the placental membrane) 4
• This pathway creates the functional units of the placenta where oxygen, nutrients, and waste products are exchanged 4

Extravillous Trophoblast Pathway

The extravillous pathway produces two specialized cell types 1, 2:

• Interstitial extravillous trophoblasts invade the decidua and a portion of the myometrium, anchoring the placenta to the uterine wall 1, 2
• Endovascular extravillous trophoblasts remodel maternal spiral arteries, transforming them into dilated, compliant vessels unresponsive to maternal vasomotor control 1, 4

Critical Early Pregnancy Events

First Trimester Vascular Remodeling

• During weeks 6-12 of pregnancy, extravillous trophoblast cells plug the spiral arteries, allowing the fetoplacental unit to develop in a low-oxygen environment 2
• At 10-12 weeks of pregnancy, the trophoblastic plugs are progressively dislocated, and the syncytiotrophoblast begins bathing in maternal blood 2
• This transition marks the establishment of full maternal-placental circulation 2

Chorioallantoic Fusion

• The allantois (an extra-embryonic structure) undergoes vasculogenesis and fuses with the chorion at approximately embryonic day 8.5 (E8.5), which is instrumental in placenta formation by E9.5 5
• The vascular plexus undergoes deep remodeling to form the umbilical artery and vein, which invade the chorion through sprouting angiogenesis 5

Functional Maturation

• As pregnancy progresses, the placenta develops terminal branches of chorionic villi where the majority of fetal-maternal exchange occurs 4
• The syncytiotrophoblast takes over maternal metabolism by secreting polypeptide hormones into maternal circulation, increasing energetic flux to the fetus 2
• The placenta synthesizes progesterone from maternal cholesterol to maintain uterine quiescence and produces estrogens using maternal and fetal adrenal androgens 2

Key Regulatory Mechanisms

• Oxygen tension is a critical regulator of trophoblast differentiation and function, with the early low-oxygen environment being essential for proper placental development 1, 2
• Transcriptional networks, hormones, growth factors (including VEGFs, PDGFs, ANGPTs, ephrins, NOTCH ligands, and WNTs), and microRNAs coordinate the differentiation process 5, 1

Clinical Significance

• Abnormal placental formation, particularly limited trophoblast invasion and failed spiral artery remodeling, causes preeclampsia and fetal growth restriction 1
• The intensity of trophoblast invasion into the uterine wall and the specificity of hormonal functions characterize human placentation 2