Effects of insufficient serine on health and selenoprotein expression in rats and their offspring

OBJECTIVE: To observe the impact of insufficient exogenous and/or endogenous serine on selenoprotein expression and health of pregnant rats and their offspring. METHOD: Experiment 1 was conducted in male rats, in which the dose-dependent effects of serine on selenoprotein expression and thyroid hormones (T3, T4 and TSH) were investigated by feeding either a serine adequate diet (20C), serine-deprived diet (20CSD) or 20CSD with different serine levels (0.5, 1.0, and 2.0 times the amount of serine in 20C). In experiment 2, a PHGDH inhibitor was administrated to pregnant rats fed either 20C or 20CSD. Blood and organ tissues of pregnant rats and offspring were subjected to the analyses of thyroid hormone, serine and homocysteine and GPx3 and SELENOP in plasma and expression of GPx1 and DIO1, 2 in tissues respectively. RESULT: In experiment 1, plasma SELENOP and GPx3 levels in adult male rats increased with the increasing dose of serine. Immunohistochemical results showed that GPx1 expression in liver and kidney of male rats also increased with increasing serine supplementation. Amongst all diet groups, only male rats fed 20CSD had significantly lower plasma TSH and T4 levels (P < 0.05). In experiment 2, GPx1 and DIO2 expression in the liver and kidney were suppressed in pregnant rats administered with a PHGDH compared to those who were not (P < 0.05). There were no significant differences in plasma T4 and T3 amongst all diet groups (P > 0.05). Also, offspring born to pregnant rats administered with a PHGDH inhibitor exhibited slower growth rates and hyperhomocysteinemia compared to offspring from mothers not administered with the inhibitor (P < 0.05). Conclusions: Insufficient exogenous serine through the diet decreased selenoprotein synthesis in adult male rats. However, this was not observed in pregnant rats, whereby exogenous or endogenous serine deficiency had no effect on the selenoprotein levels. A possible explanation is that dams may have an adaptive mechanism to limit maternal serine utilization and ensure adequate supply to the fetus.