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Volume 56
Issue 12
10.3390/medicina56120722
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Article

Tadalafil Treatment Ameliorates Hypoxia and Alters Placental Expression of Proteins Downstream of mTOR Signaling in Fetal Growth Restriction

by
Kyoka Tsuchiya
,
Kayo Tanaka
,
Hiroaki Tanaka
*,
Shintaro Maki
,
Naosuke Enomoto
,
Sho Takakura
,
Masafumi Nii
,
Kuniaki Toriyabe
,
Shinji Katsuragi
and
Tomoaki Ikeda
Department of Obstetrics and Gynecology, Mie University School of Medicine, Edobashi, Tsu 8858507, Mie, Japan
*
Author to whom correspondence should be addressed.
Medicina 2020, 56(12), 722; https://doi.org/10.3390/medicina56120722
Submission received: 11 November 2020 / Revised: 18 December 2020 / Accepted: 18 December 2020 / Published: 21 December 2020
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Abstract

Background and Objectives: Fetal growth restriction (FGR) is associated with fetal mortality and is a risk factor for cerebral palsy and future lifestyle-related diseases. Despite extensive research, no effective treatment strategy is available for FGR. Mammalian target of rapamycin (mTOR) signaling is important for the growth of fetal organs and its dysregulation is associated with miscarriage. Here, we focused on mTOR signaling and investigated how the activities of phospho-ribosomal protein S6 (rps6) and phospho-eukaryotic translation initiation factor 4E (eIF-4E), which act downstream of mTOR signaling in the human placenta, change following treatment of FGR with tadalafil and aimed to elucidate the underlying mechanism of action. Placental hypoxia was investigated by immunostaining for hypoxia-inducible factor (HIF)-2α. Materials and Methods: Phosphor-rps6 and phosphor-eIF4E expression were examined by Western blotting and enzyme-linked immunosorbent assay, respectively. Results: HIF-2α expression significantly increased in FGR placenta compared with that in the control placenta but decreased to control levels after tadalafil treatment. Levels of phospho-rps6 and phospho-eIF-4E were significantly higher in FGR placenta than in control placenta but decreased to control levels after tadalafil treatment. Conclusions: Tadalafil restored the levels of HIF-2α, phospho-rps6, and eIF-4E in FGR placenta to those observed in control placenta, suggesting that it could be a promising treatment strategy for FGR.
Keywords: fetal growth restriction; placenta; mTOR fetal growth restriction; placenta; mTOR

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MDPI and ACS Style

Tsuchiya, K.; Tanaka, K.; Tanaka, H.; Maki, S.; Enomoto, N.; Takakura, S.; Nii, M.; Toriyabe, K.; Katsuragi, S.; Ikeda, T. Tadalafil Treatment Ameliorates Hypoxia and Alters Placental Expression of Proteins Downstream of mTOR Signaling in Fetal Growth Restriction. Medicina 2020, 56, 722. https://doi.org/10.3390/medicina56120722

AMA Style

Tsuchiya K, Tanaka K, Tanaka H, Maki S, Enomoto N, Takakura S, Nii M, Toriyabe K, Katsuragi S, Ikeda T. Tadalafil Treatment Ameliorates Hypoxia and Alters Placental Expression of Proteins Downstream of mTOR Signaling in Fetal Growth Restriction. Medicina. 2020; 56(12):722. https://doi.org/10.3390/medicina56120722

Chicago/Turabian Style

Tsuchiya, Kyoka, Kayo Tanaka, Hiroaki Tanaka, Shintaro Maki, Naosuke Enomoto, Sho Takakura, Masafumi Nii, Kuniaki Toriyabe, Shinji Katsuragi, and Tomoaki Ikeda. 2020. "Tadalafil Treatment Ameliorates Hypoxia and Alters Placental Expression of Proteins Downstream of mTOR Signaling in Fetal Growth Restriction" Medicina 56, no. 12: 722. https://doi.org/10.3390/medicina56120722

APA Style

Tsuchiya, K., Tanaka, K., Tanaka, H., Maki, S., Enomoto, N., Takakura, S., Nii, M., Toriyabe, K., Katsuragi, S., & Ikeda, T. (2020). Tadalafil Treatment Ameliorates Hypoxia and Alters Placental Expression of Proteins Downstream of mTOR Signaling in Fetal Growth Restriction. Medicina, 56(12), 722. https://doi.org/10.3390/medicina56120722

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