Effect of gestational age and fetal sex on metabolism of creatine by uteri, placentae, and fetuses of pigs†.

The creatine (Cr) biosynthesis pathway buffers adenosine triphosphate in metabolically active tissues. We investigated whether sex of fetus and day of gestation influence Cr in endometrial and conceptus tissues from gilts on days 60 and 90 (n = 6 gilts/day) of gestation. Uterine and conceptus tissues associated with one male and one female fetus from each gilt were analyzed for creatine, messenger RNAs (mRNAs), and proteins for Cr biosynthesis. Total Cr decreased in amniotic fluid but increased in allantoic fluid between days 60 and 90 of gestation for male (P < 0.05) but not for female fetuses (P > 0.05). Endometrial expression of creatine kinase, muscle (CKM), creatine kinase mitochondrial type 1 (CKMT1), and solute carrier family 6, member 8 (SLC6A8) mRNAs increased (P < 0.05) between days 60 and 90 only for female fetuses. On day 60, expression of creatine kinase, brain (CKB) and CKMT1 mRNAs was greater (P < 0.05) for placentae of female than male fetuses. Livers of male fetuses had greater expression of arginine:glycine amidinotransferase (AGAT) and CKB than for females on day 60, while kidneys of female fetuses had greater expression of guanidinoacetate-N-methyltransferase (GAMT) than male fetuses on day 90 (P < 0.05). Localization of GAMT, CKB, CKMT1, and SLC6A8 proteins to uterine and chorionic epithelium was not influenced by gestational age or fetal sex. Arginine-glycine amidinotransferase localized to fetal kidneys and appeared greater on day 90 than on day 60 in both sexes. Thus, expression of the creatine-creatine kinase-phosphocreatine system at the uterine-conceptus interface is affected by gestational age and fetal sex to influence energy homeostasis in pigs.