Tadalafil treatment in mice for preeclampsia with fetal growth restriction has neuro-benefic effects in offspring through modulating prenatal hypoxic conditions

Autor:	Kenji Ikemura, Tadashi Kimura, Takashi Umekawa, Tomoaki Ikeda, Yuki Kamimoto, Kayo Tanaka, Hiroaki Tanaka, Masafumi Nii, Eiji Kondo, Masahiro Okuda, Masayuki Endoh, Ineko Kato, Ryota Tachibana, Ning Ma, Michiko Kaneda, Hiroshi Hosoda, Shintaro Maki, Shoichi Magawa, Kento Yoshikawa, Fumi Furuhashi, Takao Owa, Makoto Tsuji, Kyoko Shimada, Takekazu Miyoshi
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	0301 basic medicine medicine.medical_specialty medicine.drug_mechanism_of_action Offspring Placenta Vasodilator Agents lcsh:Medicine Article Preeclampsia Tadalafil 03 medical and health sciences Mice 0302 clinical medicine Pre-Eclampsia Pregnancy Internal medicine medicine Basic Helix-Loop-Helix Transcription Factors Animals Hypoxia lcsh:Science Fetus Multidisciplinary Fetal Growth Retardation business.industry lcsh:R Brain medicine.disease Disease Models Animal 030104 developmental biology Endocrinology medicine.anatomical_structure Treatment Outcome In utero embryonic structures Female lcsh:Q business Phosphodiesterase 5 inhibitor 030217 neurology & neurosurgery medicine.drug
Zdroj:	Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) Scientific Reports
ISSN:	2045-2322
Popis:	We have demonstrated that tadalafil facilitates fetal growth in mice with L-NG-nitroarginine methyl ester (L-NAME)-induced preeclampsia (PE) with fetal growth restriction (FGR). Tadalafil is a selective phosphodiesterase 5 inhibitor that dilates the maternal blood sinuses in the placenta, thereby facilitating the growth of the fetus. The purpose of this study was to investigate the effects of tadalafil treatment for PE and FGR on the developing brain in FGR offspring using an L-NAME-induced mouse model of PE with FGR. A control group of dams received carboxymethylcellulose (CMC). L-NAME-treated groups received L-NAME dissolved in CMC from 11 days post coitum (d.p.c.). The L-NAME-treated dams were divided into two subgroups 14 d.p.c. One subgroup continued to receive L-NAME. The other subgroup received L-NAME with tadalafil suspended in CMC. Tadalafil treatment for PE with FGR reduced the expression of hypoxia-inducible factor-2α in the placenta and in the brain of the FGR fetus. Moreover, tadalafil treatment in utero shows improved synaptogenesis and myelination in FGR offspring on postnatal day 15 (P15) and P30. These results suggest that tadalafil treatment for PE with FGR not only facilitates fetal growth, but also has neuroprotective effects on the developing brain of FGR offspring through modulating prenatal hypoxic conditions.
Databáze:	OpenAIRE
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