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

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dc.contributor.authorAreola, Emmanuel Damilare
dc.contributor.authorAdewuyi, Ifeoluwa Jesufemi
dc.contributor.authorUsman, Taofeek Olumayowa
dc.contributor.authorTamunoibuomi, God’sgift
dc.contributor.authorArogundade, Lucy Kemi
dc.contributor.authorOlaoye, Barakat
dc.contributor.authorMatt-Ojo, Deborah Damilayo
dc.contributor.authorJeje, Abdulrazaq Olatunji
dc.contributor.authorOyabambi, Adewumi Oluwafemi
dc.contributor.authorAfolayan, Enoch Abiodun
dc.contributor.authorOlatunji, Lawrence Aderemi
dc.date.accessioned2025-05-09T15:10:52Z
dc.date.available2025-05-09T15:10:52Z
dc.date.issued2021-06-14
dc.description.abstractTestosterone 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 adipo nectin/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.
dc.description.sponsorshipThis research was supported by TETFUND Institutional-Based Research fund (2019)
dc.identifier.citationAreola, E.D., Adewuyi, I.J., Usman, T.O., Tamunoibuomi, G., Arogundade, L.K., Olaoye, B., Matt-Ojo, D.D., Jeje, A.O., Oyabambi, A.O., Afolayan, E.A., & Olatunji, L.A. (2021). Sildenafil augments fetal weight and placental adiponectin in gestational testosterone-induced glucose intolerant rats. Toxicology Reports, 30 (8), 1358-1368, Published by Elsevier. Available online at: https://www.sciencedirect.com/journal/toxicology-reports/vol/8/suppl/C?page=2
dc.identifier.uri10.1016/j.toxrep.2021.06.011
dc.identifier.urihttps://uilspace.unilorin.edu.ng/handle/123456789/16570
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofseries30(8); 1358-1368
dc.subjectAdiponectin
dc.subjectPoor fetal outcome
dc.subjectAndrogen
dc.subjectPregnancy
dc.subjectPlacental inefficiency
dc.titleSildenafil augments fetal weight and placental adiponectin in gestational testosterone-induced glucose intolerant rats
dc.typeArticle

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