Creatine biosynthesis and transport by the term human placenta

Area of Science:

• Biochemistry
• Reproductive Biology
• Cellular Metabolism

Background:

• Creatine is vital for maintaining cellular energy (ATP) homeostasis.
• The creatine kinase circuit plays a role in placental ATP turnover.
• While typically synthesized via the renal-hepatic axis, some high-energy demand tissues can produce creatine endogenously.

Purpose of the Study:

• To investigate whether the human placenta possesses the enzymatic machinery for creatine synthesis.
• To determine the presence and localization of key creatine synthesis enzymes and transporters in placental tissue.

Main Methods:

• Analysis of mRNA and protein expression of arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT) using qPCR and Western blot.
• Immunohistochemistry to localize AGAT, GAMT, and the creatine transporter (SLC6A8).
• Measurement of guanidinoacetate (GAA) and creatine synthesis in placental homogenates via GC-MS and HPLC.

Main Results:

• mRNA and protein for AGAT, GAMT, and SLC6A8 were detected in the human placenta.
• AGAT was found in stromal and endothelial cells of fetal capillaries; GAMT and SLC6A8 localized to the syncytiotrophoblast.
• Placental homogenates demonstrated ex vivo synthesis of both GAA and creatine.

Conclusions:

• The term human placenta is capable of synthesizing creatine.
• This study enhances the understanding of placental energy metabolism and creatine's role within it.