Fetal Programming of Renal Dysfunction and High Blood Pressure by Chronodisruption

dc.contributor.authorMendez, Natalia
dc.contributor.authorTorres-Farfan, Claudia
dc.contributor.authorSalazar, Esteban
dc.contributor.authorBascur, Pia
dc.contributor.authorBastidas, Carla
dc.contributor.authorVergara, Karina
dc.contributor.authorSpichiger, Carlos
dc.contributor.authorHalabi, Diego
dc.contributor.authorVio, Carlos P.
dc.contributor.authorRichter, Hans G.
dc.date.accessioned2025-01-23T21:12:47Z
dc.date.available2025-01-23T21:12:47Z
dc.date.issued2019
dc.description.abstractAdverse prenatal conditions are known to impose significant trade-offs impinging on health and disease balance during adult life. Among several deleterious factors associated with complicated pregnancy, alteration of the gestational photoperiod remains largely unknown. Previously, we reported that prenatal manipulation of the photoperiod has adverse effects on the mother, fetus, and adult offspring; including cardiac hypertrophy. Here, we investigated whether chronic photoperiod shifting (CPS) during gestation may program adult renal function and blood pressure regulation. To this end, pregnant rats were subjected to CPS throughout pregnancy to evaluate the renal effects on the fetus and adult offspring. In the kidney at 18 days of gestation, both clock and clock-controlled gene expression did not display a daily pattern, although there were recurrent weaves of transcriptional activity along the 24 h in the control group. Using DNA microarray, significant differential expression was found for 1,703 transcripts in CPS relative to control fetal kidney (835 up-regulated and 868 down-regulated). Functional genomics assessment revealed alteration of diverse gene networks in the CPS fetal kidney, including regulation of transcription, aldosterone-regulated Na+ reabsorption and connective tissue differentiation. In adult offspring at 90 days of age, circulating proinflammatory cytokines IL-1 beta and IL-6 were increased under CPS conditions. In these individuals, CPS did not modify kidney clock gene expression but had effects on different genes with specific functions in the nephron. Next, we evaluated several renal markers and the response of blood pressure to 4% NaCl in the diet for 4 weeks (i.e., at 150 days of age). CPS animals displayed elevated systolic blood pressure in basal conditions that remained elevated in response to 4% NaCl, relative to control conditions. At this age, CPS modified the expression of Nhe3, Ncc, Atp1a1, Nr3c1 (glucocorticoid receptor), and Nr3c2 (mineralocorticoid receptor); while Nkcc, Col3A1, and Opn were modified in the CPS 4%+NaCl group. Furthermore, CPS decreased protein expression of Kallikrein and COX-2, both involved in sodium handling. In conclusion, gestational chronodisruption programs kidney dysfunction at different levels, conceivably underlying the prehypertensive phenotype observed in the adult CPS offspring.
dc.fuente.origenWOS
dc.identifier.doi10.3389/fendo.2019.00362
dc.identifier.issn1664-2392
dc.identifier.urihttps://doi.org/10.3389/fendo.2019.00362
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/100974
dc.identifier.wosidWOS:000471150100002
dc.language.isoen
dc.revistaFrontiers in endocrinology
dc.rightsacceso restringido
dc.subjectblood pressure
dc.subjectchronodisruption
dc.subjectkidney
dc.subjectfetal programming
dc.subjecthigh-salt diet
dc.subjecttranscriptome landscape
dc.subjectDOHaD
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleFetal Programming of Renal Dysfunction and High Blood Pressure by Chronodisruption
dc.typeartículo
dc.volumen10
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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