Does maternal-fetal transfer of creatine occur in pregnant sheep?
Our aim was to determine the disposition of creatine in ovine pregnancy and whether creatine is transferred across the placenta from mother to fetus. Pregnant ewes received either1) a continuous intravenous infusion of creatine monohydrate or saline from 122 to 131 days gestation, with maternal and fetal arterial blood and amniotic fluid samples collected daily for creatine analysis and fetal tissues collected at necropsy at 133 days for analysis of creatine content, or2) a single systemic bolus injection of [13C]creatine monohydrate at 130 days of gestation, with maternal and fetal arterial blood, uterine vein blood, and amniotic fluid samples collected before and for 4 h after injection and analyzed for creatine, creatine isotopic enrichment, and guanidinoacetic acid (GAA; precursor of creatine) concentrations. Presence of the creatine transporter-1 (SLC6A8) and l-arginine:glycine amidinotransferase (AGAT; the enzyme synthesizing GAA) proteins were determined by Western blots of placental cotyledons. The 10-day creatine infusion increased maternal plasma creatine concentration three- to fourfold (P< 0.05) without significantly changing fetal arterial, amniotic fluid, fetal tissues, or placental creatine content. Maternal arterial13C enrichment was increased (P< 0.05) after bolus [13C]creatine injection without change of fetal arterial13C enrichment. SLC6A8 and AGAT proteins were identified in placental cotyledons, and GAA concentration was significantly higher in uterine vein than maternal artery plasma. Despite the presence of SLC6A8 protein in cotyledons, these results suggest that creatine is not transferred from mother to fetus in near-term sheep and that the ovine utero-placental unit releases GAA into the maternal circulation.
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Australia.|Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia.|Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia.
Syed
S
Baharom
Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia.
Robert
R
De Matteo
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Australia.
Stacey
S
Ellery
Institute for Physical Activity and Nutrition, Deakin University, Melbourne, Australia.
Paul
P
Della Gatta
Institute for Physical Activity and Nutrition, Deakin University, Melbourne, Australia.
Clinton R
CR
Bruce
Institute for Physical Activity and Nutrition, Deakin University, Melbourne, Australia.
Greg M
GM
Kowalski
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Australia.
Nadia
N
Hale
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Australia.
Hayley
H
Dickinson
Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia.
Richard
R
Harding
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Australia.|Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia; and.
David
D
Walker
Institute for Physical Activity and Nutrition, Deakin University, Melbourne, Australia; rsnow@deakin.edu.au.
Rodney J
RJ
Snow
D000818:Animals; D003401:Creatine / Q000378:metabolism*; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000378:metabolism; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy / Q000378:metabolism; D011270:Pregnancy, Animal / Q000378:metabolism*; D012756:Sheep / Q000378:metabolism*
C004946:glycocyamine; D003401:Creatine; D005998:Glycine
creatine; fetus; guanidinoacetic acid; placenta; pregnancy