Effects of maternal nutrition during gestation on placental steroid metabolizing enzyme activity in sheep

Normal pregnancy in sheep relies heavily on placental secretion of steroids during the last half of gestation. Maternal nutrient restriction or over-nutrition has been shown to increase or decrease peripheral concentrations of steroids, respectively. The objective was to determine the effects of maternal nutrition on placental steroid metabolizing enzyme activity in sheep. Pregnant ewes (n = 60) were allocated to receive either 100% [control-fed (CON; n = 20)], 60% [restricted- fed (RES; n = 20)], or 140% [over-fed (OVER; n = 20)] of NRC requirements for TDN beginning at d 30.2 ± 0.2 of gestation. Ewes from each nutritional treatment were slaughtered at d 45 (n = 20), 90 (n = 20), or 135 (n = 20) of gestation. At slaughter the maternal (caruncle) portion of the placenta was collected for enzymatic activity analysis. Activity of cytochrome P450 1A (CYP1A), cytochrome P450 3A (CYP3A), and UDP-glucuronosyltransferase (UGT) were determined using specific luminogenic substrates. Activities were expressed relative to mg of tissue protein. Data were analyzed using MIXED procedure of SAS and the model statement included nutritional treatment, day of gestation, and their respective interaction. Main effects are discussed in the absence of nutritional treatment by gestational day interactions. Activity of CYP1A in the caruncle was not different across gestational d (P = 0.15) or nutritional treatment (P = 0.94). Similarly, activity of CYP3A in the caruncle was not different across gestational d (P = 0.29) or nutritional treatment (P = 0.98). Activity of UGT was not different across gestational d (P = 0.26). Activity of UGT in the caruncle tended (P = 0.07) to be different across nutritional treatment, whereby activity was increased (P = 0.02) by 170% in OVER compared with CON ewes. In addition, activity of UGT in the caruncle tended (P = 0.10) to be increased by 86% in OVER compared with RES ewes, while activity was not different (P = 0.50) between RES and CON ewes. In conclusion, over-fed ewes had an increase in activity of UGT in the caruncle compared with control-fed and restricted-fed ewes. Therefore, the increase in caruncle UGT could be involved in stimulating additional steroid metabolism during gestation, thereby contributing to the decrease in peripheral concentrations observed in over-fed animals.