title: Chronic maternal hypertension affects placental gene expression and differentiation in rabbits.
abstract: BACKGROUND
  Previously, we have shown that adult offspring from hypertensive rabbits develop hypertension.
  
  
  METHODS
  We aimed to determine the effects of mild (+15 mmHg) and moderate (+25 mmHg) increases in maternal blood pressure and plasma renin activity on placental differentiation and expression of components of the renin-angiotensin system and 11[beta]-hydroxysteroid dehydrogenase type 2 mRNA in rabbits. Placentas were collected from normotensive (sham), mild (2-kidney-1-cellophane wrapped; 2K-1W) and moderate (2-kidney-2-cellophane wrapped; 2K-2W) hypertensive groups at gestational age of 14, 21 and 28 days. Placental gene expression was quantified by reverse transcriptase-PCR, and morphometry was assessed by videoimage analyses of placental sections.
  
  
  RESULTS
  Fetal weight was similar between groups across gestation. In the 2K-1W group at gestational age day 14, fetal-to-placental weight ratio was increased (approximately 34%) as were volumes of fetal capillaries ([up arrow]56%) and maternal blood space at gestational age day 21 ([up arrow]55%) compared with sham (all P < 0.05). In the 2K-2W group, fetal-to-placental weight ratio was increased at gestational age day 21 (approximately 25%; P < 0.01) with an accompanying reduction in placental weight, and at gestational age day 28, volume density of fetal capillaries was increased (approximately 22%; P < 0.05). Placental renin mRNA was lower in both the 2K-1W (approximately 88%) and 2K-2W (approximately 98%) groups at gestational age day 28 (all P < 0.01). Placental 11[beta]-hydroxysteroid dehydrogenase type 2 mRNA was lower in the 2K-1W (approximately 36%) and 2K-2W (approximately 31%) groups at gestational age day 14 and greater (approximately 36%) in the 2K-2W group at gestational age day 21 (all P < 0.01). Associations between placental AT1R and AT2R mRNA and placental differentiation were disturbed by hypertension.
  
  
  CONCLUSIONS
  Mild and moderate maternal hypertension differentially alters placental structure and gene expression that may affect placental functional capacity and contribute to programming of hypertension in offspring.
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria, Australia.
authors.forename: Adelle
authors.initials: A
authors.lastname: McArdle
authors.forename: Devaki
authors.initials: D
authors.lastname: Maduwegedera
authors.forename: Karen
authors.initials: K
authors.lastname: Moritz
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Flower
authors.forename: Kate M
authors.initials: KM
authors.lastname: Denton
authors.forename: Claire T
authors.initials: CT
authors.lastname: Roberts
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000033:anatomy & histology; D015870:Gene Expression; D046110:Hypertension, Pregnancy-Induced / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D010920:Placenta / Q000378:metabolism* / Q000473:pathology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2