IGF-II and IGF-binding proteins increase dramatically during rabbit pregnancy

During pregnancy, changes in the IGF axis are associated with changes in maternal metabolism and nutrient re-partitioning which are necessary to meet the demands of a growing conceptus. The aim of this study was to assess the IGF axis, maternal weight changes and food intake in female New Zealand White rabbits (n=7) prior to breeding (day 0) and serially throughout pregnancy until term (day 30-31). The total weight of the pregnant does progressively increased from 4.03±0.06 kg (mean±S.E.M.) on day 0 to 4.47±0.07 kg on day 30 (P<0.001). Maternal tissue mass (total weight minus estimated conceptus weight) increased until day 18, plateaued to day 22/23, and then significantly declined. On day 30, the maternal tissue mass was not significantly different from the non-pregnant value, such that the final increase in total weight was due to conceptus growth. Although the does were fed ad libitum, food intake did not change until day 29 when it decreased to approximately 50% of previous intake (P<0.01). Maternal serum IGF-I was 499 ± 32 ng/ml on day 0, reached a peak of 832 ± 160 ng/ml on day 21 (P<0.02), and then declined to 341±49 ng/ml on day 30. In contrast, serum IGF-II increased dramatically from a non-pregnant level of 85 ± 14 ng/ml to 16 295 ± 2488 ng/ml on day 23 (P<0.001), and then rapidly declined (3335 ± 954 ng/ml, day 30). Changes in serum IGF-binding proteins (IGFBPs) followed a pattern similar to IGF-II, as assessed by Western-ligand blotting. All IGFBPs, especially the 45-40 kDa IGFBP-3 doublet, increased dramatically between days 12 and 24 of pregnancy, and then declined towards term. In conclusion, we observed unique and dramatic changes in the maternal serum IGF axis that corresponded to periods of maternal weight gain and loss. The tissue source of IGFs and IGFBPs remains undetermined, although it is of note that the time when major changes in the IGF axis were first observed coincided with the time of functional change from yolk sac to placenta in the rabbit.