Tesis Doctorado
EFFECT OF THE GESTATIONAL CRONODISRUPTION ON THE FUNCTION OF THE ADRENAL GLAND IN THE FETUS AND THE ADULT PROGENY
Effect of the gestatiónal cronodisruptión on the functión of the adrenal gland in the fetus and the adult progeny
Autor
Torres, Claudia
UNIVERSIDAD AUSTRAL DE CHILE
Institución
Resumen
Light at night is essential to a 24/7 society, but it has negative consequences on health. Basically, light at night induces an alteration of our biological clocks, known as chronodisruption with effects even when this occurs during pregnancy. Indeed, an abnormal photoperiod during gestation alters fetal development, inducing long term-effects on the offspring. Here we explored the developmental impact of gestational chronodisruption (chronic photoperiod shift - CPS) on fetal and adult adrenal biorhythm and function. For instance, fetal adrenal glands had blunt daily rhythms of corticosterone, core clock gene machinery, and the genes related with corticosterone synthesis. Microarray analysis revealed significant changes in Lipid Metabolism, Small Molecule Biochemistry, and the Inflammatory Response pathway that agrees with fetal adrenal dysfunction. Regarding other developmental effects on CPS progeny, adult rats gestated under CPS lose the nocturnal melatonin peak and had a free running corticosterone rhythms. At the adrenal level, there were molecular, morphological, and physiological differences among control and CPS offspring, suggesting major desynchronization of the adrenal circadian clock and steroidogenic pathway. Additionally, to better understand the impact of chronodisruption during pregnancy on adult life physiology, we compared gestational chronodisruption with adult life chronodisruption exposition. Our data demonstrate that pregnancy is a critical windows for fetus development and especially the adrenal function, highly sensitive to programming by chronodisruption until adult life. Moreover, melatonin administration to pregnant rats exposed to CPS restored corticosterone rhythm synchronization in the offspring, but not AM-PM corticosterone response to an ACTH challenge. Altogether, the present results demonstrate that gestational chronodisruption altered fetal and adult adrenal function. This could translate to long-term abnormal stress responses and metabolic adaptation, increasing the risk of developing chronic diseases, such as metabolic syndrome and cardiovascular malfunction in adulthood.