What is the function of human chorionic gonadotropin (hCG) on the placenta?

Function of Human Chorionic Gonadotropin (hCG) on the Placenta

Human chorionic gonadotropin (hCG) serves multiple critical functions on the placenta, primarily promoting trophoblast invasion and placental development, which directly impacts fetal growth, maternal immune tolerance, and pregnancy maintenance.

Primary Functions of hCG on the Placenta

Trophoblast Invasion and Placental Development

• hCG is the first hormonal message from the placenta to the mother, detectable in maternal blood just two days after implantation 1
• Different glycoforms of hCG have distinct functions:
  • Regular hCG promotes formation of the syncytiotrophoblast (the endocrine tissue of the placenta) 2
  • Hyperglycosylated hCG (hCG-H) specifically stimulates trophoblast invasion and angiogenesis by interacting with the TGFβ receptor in a pathway independent of the LH/CG receptor 1, 3

Spiral Artery Remodeling

• hCG-H plays a key role in promoting extravillous cytotrophoblast cells to infiltrate the decidua and remodel spiral arteries into low-resistance, larger-diameter vessels 3
• This vascular remodeling is crucial for adequate placental perfusion and fetal growth

Maintenance of Early Pregnancy

• Acts as a super LH agonist, stimulating progesterone secretion by the corpus luteum until the placenta itself produces sufficient progesterone 1
• Contributes to myometrial quiescence (preventing uterine contractions) 1
• Facilitates local immune tolerance at the maternal-fetal interface 1

Structure and Production of hCG

• hCG is a complex glycoprotein composed of two highly glycosylated subunits:

  • α-subunit: identical to pituitary gonadotropin hormones (LH, FSH, TSH), contains two N-glycosylation sites, encoded by a single gene (CGA) 1
  • β-subunit: specific to hCG, contains two sites of N-glycosylation and four sites of O-glycosylation, encoded by a cluster of genes (CGB) 1

• Production sources:

  • Primarily secreted by the syncytiotrophoblast into maternal blood 2
  • Also secreted by invasive extravillous trophoblast (iEVT) 1
  • Peaks at 8-10 weeks of gestation at approximately 100,000 mIU/mL 4

Clinical Implications of hCG in Placental Function

Impact on Fetal Growth

• Low hCG concentrations in late first trimester (11-12 weeks) are associated with decreased fetal growth for both male and female fetuses 5
• High hCG concentrations during late first trimester are associated with increased fetal growth, but only in female fetuses 5
• Impaired trophoblast invasion and inadequate remodeling of uterine arteries leads to defective placental perfusion and potential fetal growth restriction 3

Abnormal hCG Levels and Pregnancy Complications

• Abnormally high hCG levels (≥2 MoM) may be associated with increased risk of preeclampsia and preterm delivery 6
• Elevated hCG levels (>100,000 mIU/mL) at 6 weeks may indicate multiple gestation or gestational trophoblastic disease 4
• In gestational trophoblastic disease, hCG is a key marker for diagnosis and monitoring 7

Diagnostic Value

• hCG-H represents a potential serum marker of implantation and early trophoblast invasion 1
• Different glycoforms of hCG can be used to monitor normal versus pathological pregnancies 2
• Maternal concentration and glycan structure of hCG change throughout pregnancy, reflecting different biological activities essential for pregnancy outcome 1

Clinical Pitfalls and Considerations

• hCG exists in multiple molecular forms (intact heterodimer, total beta hCG, free beta-subunit, degraded forms), which can affect test interpretation 4
• The glycosylation state of hCG varies with pregnancy stage, production source, and in pathological conditions 1
• Management decisions should not be based solely on a single hCG level but rather on the combination of hCG and ultrasound findings 4
• False-positive hCG results can occur due to heterophilic antibodies, cross-reactivity with luteinizing hormone, marijuana use, and hypogonadism 4

Understanding the complex functions of hCG on the placenta is essential for interpreting hCG levels in clinical practice and recognizing its role in maintaining healthy pregnancy and fetal development.