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

Functions of Human Chorionic Gonadotropin (hCG) in the Placenta

Human chorionic gonadotropin (hCG) is the first hormonal message from the developing placenta to the mother, serving multiple critical functions including maintaining corpus luteum progesterone production, promoting trophoblast invasion, supporting placental angiogenesis, and ensuring myometrial quiescence throughout pregnancy. 1, 2, 3

Basic Characteristics of hCG

• hCG is a complex glycoprotein produced by trophoblastic cells, detectable in maternal blood just after implantation 1
• Composed of two highly glycosylated subunits:
  • Alpha subunit: Identical to pituitary gonadotropin hormones (LH, FSH, TSH)
  • Beta subunit: Unique to hCG, contains two N-glycosylation sites and four O-glycosylation sites 2
• Serum values exceeding 5 mIU/mL indicate pregnancy 4, 1
• hCG levels typically peak at 8-10 weeks gestation and begin to decline thereafter 1, 2

Primary Functions of hCG in Pregnancy

1. Maintenance of Corpus Luteum

• Acts as a "super LH agonist" by binding to the LH/CG receptor
• Stimulates progesterone secretion by the corpus luteum during early pregnancy
• Maintains progesterone production until the placenta itself takes over this function (typically around 7-9 weeks) 2, 3

2. Trophoblast Development and Invasion

• Different forms of hCG have distinct roles in trophoblast development:
  • Regular hCG: Promotes formation of syncytiotrophoblast
  • Hyperglycosylated hCG (hCG-H): Stimulates trophoblast invasion through interaction with TGFβ receptor 2 (independent of LH/CG receptor) 3, 5
• hCG-H is particularly elevated during early first trimester, corresponding to the trophoblastic invasion process 2, 5

3. Placental Angiogenesis and Vascular Development

• Maintains myometrial and decidual spiral arteries
• Supports vascular supply of the placenta throughout pregnancy
• Promotes angiogenesis through LH/CG receptor signaling 2, 3, 6

4. Immune Modulation

• Contributes to local immune tolerance at the maternal-fetal interface
• Helps prevent rejection of the semi-allogeneic fetus 2, 3

5. Myometrial Quiescence

• Helps maintain uterine quiescence during pregnancy
• Prevents premature contractions 2, 3

Different Forms of hCG and Their Specific Functions

1. Regular hCG:

   • Produced by syncytiotrophoblast cells
   • Primary endocrine function maintaining corpus luteum
   • Supports placental vascular supply throughout pregnancy 7, 6

2. Hyperglycosylated hCG (hCG-H):

   • Produced by extravillous cytotrophoblast cells
   • Acts as an autocrine factor controlling trophoblast invasion
   • Critical for implantation and establishment of hemochorial placentation
   • Inhibits apoptosis in extravillous invasive cytotrophoblast cells 7, 6, 5

3. Free Beta-subunit of hCG:

   • Can be produced by certain malignancies
   • Functions as an autocrine factor antagonizing apoptosis 7, 6

Clinical Significance

• hCG measurement is essential in:
  • Pregnancy confirmation (values >5 mIU/mL indicate pregnancy) 4, 1
  • First trimester screening for fetal aneuploidy (combined with PAPP-A and NT) 1
  • Monitoring gestational trophoblastic disease 4, 1
  • Abnormally high levels may indicate gestational trophoblastic disease 4, 1
  • Decreased levels of hCG-H may be associated with intrauterine growth restriction 5

Important Considerations

• Different laboratories may use different assays with varying reference ranges 4, 1
• The glycosylation state of hCG varies with pregnancy stage and in pathological conditions 2, 3
• In rare cases, elevated hCG may be unrelated to pregnancy (e.g., pituitary dysfunction or neoplasia) 4, 1

Understanding the diverse functions of hCG and its variants is crucial for comprehending early pregnancy physiology and diagnosing pregnancy-related complications.