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Creatine metabolism at the uterine-placental interface throughout gestation in sheep.

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The placenta requires high levels of ATP to maintain a metabolically active state throughout gestation. The creatine (Cr)-creatine kinase (CK)-phosphocreatine (PCr) system is known to buffer ATP levels; however, the… Click to show full abstract

The placenta requires high levels of ATP to maintain a metabolically active state throughout gestation. The creatine (Cr)-creatine kinase (CK)-phosphocreatine (PCr) system is known to buffer ATP levels; however, the role(s) Cr-CK-PCr system plays in uterine and placental metabolism throughout gestation is poorly understood. In this study, Suffolk ewes were ovariohysterectomized on Days 30, 50, 70, 90, 110 and 125 of gestation (n = 3-5 ewes/per day, except n = 2 on Day 50) and uterine and placental tissues subjected to analyses to measure metabolites, mRNAs, and proteins related to the Cr-CK-PCr system. Day of gestation affected concentrations and total amounts of guanidinoacetate (GA) and Cr in maternal plasma, amniotic fluid and allantoic fluid (P < 0.05). Expression of mRNAs for arginine:glycine amidinotransferase (AGAT), guanidinoacetate methyltransferase (GAMT), creatine kinase B (CKB), and solute carrier (SLC)16A12 in endometria and for AGAT and CKB in placentomes changed significantly across days of gestation (P < 0.05). AGAT protein was more abundant in uterine luminal epithelium (LE) on Days 90 and 125 compared to Days 30 and 50 (P < 0.01). The chorionic epithelium (CE) of placentomes expressed GAMT and SLC6A13 throughout gestation. Cr transporter (SLC6A8) was expressed by the uterine LE and trophectoderm of placentomes throughout gestation. Creatine kinase (CKB and CKMT1) proteins were localized primarily to the uterine LE and to the placental CE of placentomes throughout gestation. Collectively, these results demonstrate cell-specific and temporal regulation of components of the Cr-CK-PCr system that likely influence energy homeostasis for fetal-placental development.

Keywords: creatine; throughout gestation; uterine placental; gestation; pcr system

Journal Title: Biology of reproduction
Year Published: 2023

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