Effects of N-carbamylglutamate on steroidogenesis and relative abundances of mRNA transcripts in pig placental trophoblasts.

Supplementation of N-carbamylglutamate (NCG) improves gestation outcomes, with increased piglet within-litter uniformity of birth weight and reduced peripheral steroid concentrations in pregnant sows and ewes. It was hypothesized that the effect of NCG on placental function results from direct effects on the placental trophoblasts. There, therefore, was investigation of the effects of NCG on pig placental trophoblast (pTr) steroidogenesis, mRNA transcript abundance, and cell proliferation in vitro. The pTr were treated with NCG in serum-free medium for 24-48 h. Treatment with NCG inhibited pTr progesterone, androstenedione, testosterone (all P <  0.01), and estradiol (P <  0.05) production, whereas it promoted (P <  0.05) pTr proliferation. Treatment with NCG suppressed (P <  0.05) the relative abundances of CYP11A1, CYP19A1, and CASP3 and increased abundances of CCDN1 (P <  0.01) and CDK4 (P <  0.05) mRNA transcripts in pTr, whereas NCG treatment had no effect (P >  0.10) on relative abundances of StAR, HSD17B4, or HSD3B mRNA transcripts. Treatments with NCG can increase pTr cell numbers of sows through upregulating CCND1 and CDK4 and suppressing CASP3 mRNA transcript abundances, while modulating steroidogenesis through effects on CYP11A1 and CYP19A1 mRNA transcript abundances. It is concluded that NCG may have a direct action on pTr and may regulate placental function by suppressing pTr differentiation as a consequence of lesser steroid synthesis while promoting pTr proliferation and inhibiting apoptosis in sows.