title: Local intra-uterine Ang-(1-7) infusion attenuates PGE2and 6-keto PGF1αin decidualized uterus of pseudopregnant rats.
abstract: Cyclooxygenase (COX)-derived prostanoids (PGE2,PGI2) are important contributors to the process of decidualization. Previous studies showed the presence of Ang-(1-7) in the primary and secondary decidualized zones of the implantation site at early pregnancy. Decreased concentrations of Ang-(1-7) were found in the decidualized uterus compared to the non-decidualized uterus of pseudopregnant rats, suggesting that low levels of Ang-(1-7) are required for successful decidualization at early pregnancy.
  
  
  
  To understand the role of Ang-(1-7) in prostaglandin production in a decidualized uterus, induced by a bolus injection of sesame oil, Ang-(1-7) (24 μg/kg/h) or vehicle was then infused directly into the decidualized uterine horn using an osmotic minipump. The right horns were not injected or infused and served as non-decidualized uterine horns in both groups of animals.
  
  
  
  Decidualization increased PGE2concentration in the uterus (0.53 ± 0.05 vs. 12.0 ± 3.2 pmol/mg protein, p < 0.001, non-decidualized vs. decidualized horns); Ang-(1-7) infusion attenuated the increase of PGE2(12.0 ± 3.2 vs. 5.1 ± 1.3 pmol/mg protein, p < 0.01 control vs. Ang-(1-7) treated decidualized horns). The stable metabolite of PGI2(6-keto PGF1α) was increased with decidualization (0.79 ± 0.17 vs. 3.5 ± 0.82 pmol/mg protein, p < 0.001, non-decidualized vs. decidualized horns). Ang-(1-7) infusion attenuated the increase in 6-keto PGF1αin the decidualized horn (3.5 ± 0.82 vs 1.8 ± 0.37 pmol/mg protein, p < 0.05 control vs. Ang-(1-7) treated decidualized horns). The circulating levels of 6-keto-PGF1aand TXB2were decreased by Ang-(1-7) infusion, while no difference was observed in circulating PGE2. Although the global assessment of cleaved caspase 3 immunostaining, a marker of apoptosis, was unchanged within the Ang-(1-7) decidualized horn, there were localized decreases in cleaved caspase 3 staining in the luminal region in the decidualized uterus of Ang-(1-7)-treated rats.
  
  
  
  These studies show that increased local uterine Ang-(1-7) alters the uterine prostaglandin environment, possibly leading to disruptions of early events of decidualization.
authors.affiliation: Hypertension and Vascular Research, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC, 27157-1032, USA. bbrosnih@wakehealth.edu.
authors.forename: K Bridget
authors.initials: KB
authors.lastname: Brosnihan
authors.affiliation: Hypertension and Vascular Research, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC, 27157-1032, USA.|Department of Obstetrics & Gynecology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC, 27157-1032, USA.|Biomedical Research Infrastructure Center, Winston Salem State University, Winston-Salem, NC, USA.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Pulgar
authors.affiliation: Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Manish S
authors.initials: MS
authors.lastname: Bharadwaj
authors.affiliation: Hypertension and Vascular Research, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC, 27157-1032, USA.
authors.forename: Liomar A A
authors.initials: LA
authors.lastname: Neves
authors.affiliation: Hypertension and Vascular Research, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC, 27157-1032, USA.
authors.forename: Liliya M
authors.initials: LM
authors.lastname: Yamaleyeva
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000803:Angiotensin I / Q000008:administration & dosage*; D000818:Animals; D003656:Decidua / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D010446:Peptide Fragments / Q000008:administration & dosage*; D011247:Pregnancy; D011555:Pseudopregnancy / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D015121:6-Ketoprostaglandin F1 alpha; D000803:Angiotensin I; C118790:angiotensin I (1-7); D015232:Dinoprostone
keywords: Angiotensin-(1-7); Apoptosis; Decidualization; Early pregnancy; Prostanoids; Pseudopregnancy