Sildenafil augments fetal weight and placental adiponectin in gestational testosterone-induced glucose intolerant rats.

Autor:	Areola ED; HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria., Adewuyi IJ; HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria., Usman TO; HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria.; Cardiovascular Unit, Department of Physiology, College of Health Sciences, Osun State University, Osogbo, Nigeria., Tamunoibuomi G; HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria., Arogundade LK; HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria., Olaoye B; HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria., Matt-Ojo DD; HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria., Jeje AO; HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria., Oyabambi AO; HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria., Afolayan EA; Department of Pathology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria., Olatunji LA; HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria.
Jazyk:	angličtina
Zdroj:	Toxicology reports [Toxicol Rep] 2021 Jun 30; Vol. 8, pp. 1358-1368. Date of Electronic Publication: 2021 Jun 30 (Print Publication: 2021).
DOI:	10.1016/j.toxrep.2021.06.011
Abstrakt:	Testosterone induces intra-uterine growth restriction (IUGR) with maternal glucose dysregulation and oxidant release in various tissues. Adiponectin, which modulates the antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) signaling is expressed in the placenta and affects fetal growth. Sildenafil, a phosphodiesterase type 5 inhibitor (PDE5i), used mainly in erectile dysfunction has been widely studied as a plausible pharmacologic candidate in IUGR. Therefore, the present study sought to determine the effect of PDE5i on placental adiponectin/Nrf2 pathway in gestational testosterone-induced impaired glucose tolerance and fetal growth. Fifteen pregnant Wistar rats were allotted into three groups (n = 5/group) receiving vehicles (Ctr; distilled water and olive oil), testosterone propionate (Tes; 3.0 mg/kg; sc) or combination of testosterone propionate (3.0 mg/kg; sc) and sildenafil (50.0 mg/kg; po ) from gestational day 14-19. On gestational day 20, plasma and placenta homogenates were obtained for biochemical analysis as well as fetal biometry. Pregnant rats exposed to testosterone had 4-fold increase in circulating testosterone compared with control (20.9 ± 2.8 vs 5.1 ± 1.7 ng/mL; p < 0.05) whereas placenta testosterone levels were similar in testosterone- and vehicle-treated rats. Exposure to gestational testosterone caused reduction in fetal and placental weights, placental Nrf2 and adiponectin. Moreover, impaired glucose tolerance, elevated plasma triglyceride-glucose (TyG) index, placental triglyceride, total cholesterol, lactate, malondialdehyde and alanine aminotransferase were observed in testosterone-exposed rats. Treatment with sildenafil improved glucose tolerance, plasma TyG index, fetal and placental weights and reversed placental adiponectin in testosterone-exposed pregnant rats without any effect on placental Nrf2. Therefore, in testosterone-exposed rats, sildenafil improves impaired glucose tolerance, poor fetal outcome which is accompanied by augmented placental adiponectin regardless of depressed Nrf2. Competing Interests: The authors report no declarations of interest. (© 2021 The Authors. Published by Elsevier B.V.)
Databáze:	MEDLINE
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