Extraembryonic metabolism of corticosterone protects against effects of exposure

When females experience stress during reproduction, developing embryos can be exposed to elevated levels of glucocorticoids, which can permanently affect offspring development, physiology, and behavior. However, the embryo can regulate exposure to glucocorticoids. In placental species, the placenta regulates embryonic exposure to maternal steroids via metabolism. In a comparable way, recent evidence has shown the extraembryonic membranes of avian species also regulate embryonic exposure to a number of maternal steroids deposited in the yolk via metabolism early in development. However, despite the known effects of embryonic exposure to glucocorticoids, it is not yet understood how glucocorticoids are metabolized early in development. To address this knowledge gap, we injected corticosterone into freshly laid chicken (Gallus gallus) eggs and identified corticosterone metabolites, located metabolomic enzyme transcript expression, tracked metabolomic enzyme transcript expression during the first six days of development, and determined the effect of corticosterone and metabolites on embryonic survival. We found that yolk corticosterone was metabolized before day four of development into two metabolites: 5β-corticosterone and 20β-corticosterone. The enzymes, AKR1D1 and CBR1 respectively, were expressed in the extraembryonic membranes. Expression was dynamic during early development, peaking on day two of development. Finally, we found that corticosterone exposure is lethal to the embryos, yet exposure to the metabolites is not, suggesting that metabolism protects the embryo. Ultimately, we show that the extraembryonic membranes of avian species actively regulate their endocrine environment very early in development.