Maternal corticosterone exposure in the mouse programs sex-specific renal adaptations in the renin-angiotensin-aldosterone system in 6-month offspring.
Short-term maternal corticosterone (Cort) administration at mid-gestation in the mouse reduces nephron number in both sexes while programming renal and cardiovascular dysfunction in 12-month male but not female offspring. The renal renin-angiotensin-aldosterone system (RAAS), functions in a sexually dimorphic manner to regulate both renal and cardiovascular physiology. This study aimed to identify if there are sex-specific differences in basal levels of the intrarenal RAAS and to determine the impact of maternal Cort exposure on the RAAS in male and female offspring at 6 months of age. While intrarenal renin concentrations were higher in untreated females compared to untreated males, renal angiotensin II concentrations were higher in males than females. Furthermore, basal plasma aldosterone concentrations were greater in females than males. Cort exposed male but not female offspring had reduced water intake and urine excretion. Cort exposure increased renal renin concentrations and elevated mRNA expression of Ren1, Ace2, and Mas1 in male but not female offspring. In addition, male Cort exposed offspring had increased expression of the aldosterone receptor, Nr3c2 and renal sodium transporters. In contrast, Cort exposure increased Agtr1a mRNA levels in female offspring only. This study demonstrates that maternal Cort exposure alters key regulators of renal function in a sex-specific manner at 6 months of life. These finding likely contribute to the disease outcomes in male but not female offspring in later life and highlights the importance of renal factors other than nephron number in the programming of renal and cardiovascular disease.
School of Biomedical Science, The University of Queensland, St Lucia, Australia.
James S M
JS
Cuffe
School of Biomedical Science, The University of Queensland, St Lucia, Australia.
Danielle J
DJ
Burgess
School of Biomedical Science, The University of Queensland, St Lucia, Australia.
Lee
L
O'Sullivan
School of Biomedical Science, The University of Queensland, St Lucia, Australia.
Reetu R
RR
Singh
School of Biomedical Science, The University of Queensland, St Lucia, Australia k.moritz@uq.edu.au.
Karen M
KM
Moritz
D000804:Angiotensin II / Q000096:biosynthesis; D000818:Animals; D015153:Blotting, Western; D003345:Corticosterone / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000032:analysis; D012083:Renin / Q000096:biosynthesis; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics
C000715471:Mas1 protein, mouse; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D000804:Angiotensin II; D012083:Renin; D003345:Corticosterone
RAS; fetal programming; kidney; sex specific