TY - JOUR
T1 - Tadalafil alleviates preeclampsia and fetal growth restriction in RUPP model of preeclampsia in mice
AU - Sekimoto, Akiyo
AU - Tanaka, Kayo
AU - Hashizume, Yamato
AU - Sato, Emiko
AU - Sato, Hiroshi
AU - Ikeda, Tomoaki
AU - Takahashi, Nobuyuki
N1 - Funding Information:
We thank Dr. Takashi Umekawa and members of Tohoku University, Faculty of Pharmaceutical Sciences and members of Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine for their assistance. Our work was supported by grants-in-aid from the Japan Society for the Promotion of Science (JSPS18K09247, 19K09800), Japan. This work is partially supported by Tohoku University Center for Gender Equality PromotionSupport Project (Project to Promote Gender Equality and Female Researchers).
Funding Information:
We thank Dr. Takashi Umekawa and members of Tohoku University, Faculty of Pharmaceutical Sciences and members of Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine for their assistance. Our work was supported by grants-in-aid from the Japan Society for the Promotion of Science ( JSPS18K09247 , 19K09800 ), Japan. This work is partially supported by Tohoku University Center for Gender Equality Promotion Support Project (Project to Promote Gender Equality and Female Researchers).
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2020/1/15
Y1 - 2020/1/15
N2 - Background: – Tadalafil, a long-acting phosphodiesterase 5 (PDE5) inhibitor, alleviates preeclampsia (PE), and decreases the fetal and infant deaths associated with fetal growth restriction (FGR) in phase II clinical trial. Recently, we demonstrated that tadalafil alleviates FGR and hypertension in the dams with PE induced by L-NAME. Objective: –The aim of present study was to clarify the effect of tadalafil in another mouse model of PE, murine reduced uterine perfusion pressure (RUPP) model we have recently developed. Methods: –At 14.5 dpc we performed RUPP operation in mice to induce PE, administered the animals with tadalafil or vehicle in the drinking water daily from 15.5 dpc, and sacrificed them at 18.5 dpc for analyses. Results: –Tadalafil improved maternal hypertension and glomerular endotheliosis in RUPP mice. Moreover, tadalafil prolonged pregnancy period, and improved survival and growth of the embryos. RUPP increased content of sFlt-1 protein in the placenta, and tadalafil corrected it back to control levels. Conclusion: – Tadalafil alleviates PE-like phenotype and FGR in RUPP murine model. RUPP model could help understand the mechanism of how tadalafil works on PE and FGR.
AB - Background: – Tadalafil, a long-acting phosphodiesterase 5 (PDE5) inhibitor, alleviates preeclampsia (PE), and decreases the fetal and infant deaths associated with fetal growth restriction (FGR) in phase II clinical trial. Recently, we demonstrated that tadalafil alleviates FGR and hypertension in the dams with PE induced by L-NAME. Objective: –The aim of present study was to clarify the effect of tadalafil in another mouse model of PE, murine reduced uterine perfusion pressure (RUPP) model we have recently developed. Methods: –At 14.5 dpc we performed RUPP operation in mice to induce PE, administered the animals with tadalafil or vehicle in the drinking water daily from 15.5 dpc, and sacrificed them at 18.5 dpc for analyses. Results: –Tadalafil improved maternal hypertension and glomerular endotheliosis in RUPP mice. Moreover, tadalafil prolonged pregnancy period, and improved survival and growth of the embryos. RUPP increased content of sFlt-1 protein in the placenta, and tadalafil corrected it back to control levels. Conclusion: – Tadalafil alleviates PE-like phenotype and FGR in RUPP murine model. RUPP model could help understand the mechanism of how tadalafil works on PE and FGR.
KW - Fetal growth restriction
KW - Phosphodiesterase 5 inhibitor
KW - Preeclampsia
KW - Reduced uterine perfusion pressure model
KW - Tadalafil
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U2 - 10.1016/j.bbrc.2019.10.186
DO - 10.1016/j.bbrc.2019.10.186
M3 - Article
C2 - 31703840
AN - SCOPUS:85075332866
SN - 0006-291X
VL - 521
SP - 769
EP - 774
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -