Diabetes consequences in the fetus liver of the non-obese diabetic mice

Abstract

DM type 1 (T1D) incidence is increasing around 3% every year and represents risks for maternal and fetal health. The objective of this study was to explore the effects of diabetes on fetus liver cells in non-obese diabetic (NOD) mice. Hyperglycemic NOD (HNOD), normoglycemic NOD (NNOD) and BALB/c females were used for mating, and the fetus livers were collected at 19.5 gestation day (gd). HNOD group had reduced fetal weight (989.5±68.32 vs 1290±57.39 mg BALB/c, P<0.05) at 19.5 gd and higher glycemia (516.66±28.86 mg dl^-1, P<0.001) at both 0.5 gd and 19.5 gd compared to other groups. The protein expression of albumin (ALB) was significantly reduced in HNOD group (0.9±0.2 vs 3.36±0.36 NNOD P<0.01, vs 14.1±0.49 BALB/c P<0.001). Reduced gene expression of ALB (1.34±0.12 vs 5.53±0.89 NNOD and 5.23±0.71 BALB/c, P<0.05), Hepatic Nuclear Factor-4 alpha (HNF-4α) (0.69±0.1 vs 3.66±0.36 NNOD, P<0.05) and miR-122 (0.27±0,10 vs 0.88±0.15 NNOD, P<0.05) was present in HNOD group. No difference for alpha-Fetoprotein (AFP) and gene expression was observed. In conclusion, our findings show the impacts of T1D on the expression of ALB, AFP, HNF-4α and miR-122 in fetus liver cells by using NNOD and HNOD mice.

Figure 1

Representative dot plot of fetus liver cells from BALB/c, NNOD and HNOD groups at 19.5 dg stained with Albumin (ALB) and Alpha-Fetoprotein (AFP) markers. The histogram show increased expression of ALB in HNOD group compared to NNOD and BALB/c groups. The expression of AFP was not different between groups. Results represent SEM of liver cells collected from fetus livers per animal of control (n=6), NNOD (n=6) and HNOD groups (n=6) analyzed in duplicate, **P<0.01, ****P<0.0001.

Figure 2

Albumin (ALB), alpha-fetoprotein (AFP), Hepatic nuclear factor-4 (HNF-4α) mRNAs and miR-122 expression levels in fetus liver cells of BALB/c, NNOD and HNOD groups at 19.5 dg. Each NNOD and HNOD sample was normalized to a BALB/c sample and, the expression level of ALB, AFP, HNF-4α was calculated by application of ΔΔCt method and the miR-122 fold expression by 2^−ΔΔCt method. The data represent SEM of liver cells collected from fetus livers per animal of control (n=6), NNOD (n=6) and HNOD groups (n=6) analyzed in duplicate, *P<0.05.