Creatine phosphagen system regulates energy metabolism and growth of trophoblasts

Disrupting creatine/PCr metabolism with cyclocreatine (20 mM) in primary human trophoblast stem cells reduces proliferation, arrests the cell cycle, and increases apoptosis.

• Why it matters: The creatine (Cr)-creatine kinase (CK)-phosphocreatine (PCr) system supports ATP homeostasis, but its role in early human placental development and trophoblast growth is poorly defined.
• What they did: Across first- to term human placentae (n=3–6/group), Cr-CK-PCr components showed gestational age- and compartment-specific localization, and trophoblast function was tested by treating primary hTSCs and trophoblast organoids with cyclocreatine (0–40 mM) for 48 h.
• The result: Cyclocreatine impaired mitochondrial and glycolytic function (P<0.01) and reduced organoid growth and EGFR expression (P<0.05), supporting that Cr/PCr disruption compromises trophoblast bioenergetics, proliferation, and survival.