Prenatal dexamethasone-induced programmed hypertension and renal programming.
OBJECTIVE
Antenatal glucocorticoids can induce long-term effects on offspring health, including hypertension. Programmed hypertension has been observed in a prenatal dexamethasone (DEX) exposure model. However, how renal programming responds to prenatal DEX at different stages of development and the impact of DEX on programmed hypertension remain unclear. Therefore, we utilized RNA next-generation sequencing (NGS) to analyze the renal transcriptome in the offspring to examine whether key genes and pathways are responsible for DEX-induced renal programming and hypertension.


METHODS
Pregnant rats received intraperitoneal dexamethasone from gestational day 16 to 22. Prenatal DEX-induced programmed hypertension was examined in male offspring at 16 weeks of age.


RESULTS
Prenatal DEX modified 431 renal transcripts from the nephrogenesis stage to adulthood in a constant manner. At the pre-hypertensive and established hypertension stages, we identified 11 and 13 differentially expressed genes related to blood pressure regulation, respectively. Among these genes, Npr3, Ptgs2, Agt, Edn3, Ephx2, Agtr1b, and Gucy1a3 are associated with endothelium-derived hyperpolarizing and contractile factors (EDHF and EDCF). Genes in the arachidonic acid metabolism pathway may potentially be key genes contributing to programmed hypertension. In addition, DEX induced soluble epoxide hydrolase expression (Ephx2 gene encoding protein).


CONCLUSIONS
Prenatal DEX elicits an imbalance between EDHFs and EDCFs that might lead to renal programming and hypertension. The arachidonic acid metabolism pathway is a common pathway contributing to programmed hypertension. Our results highlight candidate genes and pathways involved in renal programming as targets for therapeutic approaches to prevent programmed hypertension in children exposed to antenatal corticosteroids.
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
Jiunn-Ming
JM
Sheen
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
Hong-Ren
HR
Yu
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
Mao-Meng
MM
Tiao
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
Chih-Cheng
CC
Chen
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan; Department of Traditional Chinese Medicine, Chang Gung University, Linkow, Taiwan.
Li-Tung
LT
Huang
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
Hsin-Yu
HY
Chang
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan; Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan. Electronic address: tainyl@hotmail.com.
You-Lin
YL
Tain
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001794:Blood Pressure / Q000235:genetics; D015153:Blotting, Western; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006973:Hypertension / Q000139:chemically induced*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects*
D016718:Arachidonic Acid; D003907:Dexamethasone
Arachidonic acid; Endothelium-derived contractile factor; Endothelium-derived hyperpolarizing factor; Glucocorticoid; Hypertension; Next-generation sequencing