The Effects of Flavonoid Apigenin on Male Reproductive Health: Inhibition of Spermatogonial Proliferation through Downregulation of <em>Prmt7</em>/<em>Akt3</em> Pathway

Apigenin, a common dietary flavonoid abundantly present in a variety of fruits and vegetables, has promising anticancer properties. As an effector of apigenin in myoblasts, protein arginine methyltransferase 7 (<i>Prmt7</i>) is required for male germ cell development. However, whether ap...

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Autores principales: Bingyuan Wang, Mingrui Zhang, Jiankang Guo, Zhiguo Liu, Rong Zhou, Fei Guo, Kui Li, Yulian Mu
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:d435b2e721964d0f99bd1a340da5a1b42021-11-25T17:54:21ZThe Effects of Flavonoid Apigenin on Male Reproductive Health: Inhibition of Spermatogonial Proliferation through Downregulation of <em>Prmt7</em>/<em>Akt3</em> Pathway10.3390/ijms2222122091422-00671661-6596https://doaj.org/article/d435b2e721964d0f99bd1a340da5a1b42021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12209https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Apigenin, a common dietary flavonoid abundantly present in a variety of fruits and vegetables, has promising anticancer properties. As an effector of apigenin in myoblasts, protein arginine methyltransferase 7 (<i>Prmt7</i>) is required for male germ cell development. However, whether apigenin may influence male reproductive health through <i>Prmt7</i> is still unclear. To this end, mouse spermatogonia were treated with different concentrations (2.5 to 50 μM) of apigenin for 48 h, which showed that apigenin could cause reduced cell proliferation in conjunction with longer S phase and G2/M phase (with concentrations of 10 and 20 μM, respectively), and increased apoptosis of spermatogonia (with concentration of 20 μM). Reduced <i>Prmt7</i> expression was found in 20 μM apigenin-treated spermatogonia. Moreover, siRNA-induced <i>Prmt7</i> knockdown exhibited similar influence on spermatogonia as that of apigenin treatment. In mechanistic terms, transcriptome analysis revealed 287 differentially expressed genes between <i>Prmt7</i>-downregulated and control spermatogonia. Furthermore, rescue experiments suggested that the effects of apigenin on spermatogonia might be mediated through the <i>Prmt7</i>/<i>Akt3</i> pathway. Overall, our study supports that apigenin can interfere with mouse spermatogonial proliferation by way of the downregulated <i>Prmt7</i>/<i>Akt3</i> pathway, which demonstrates that the concentration should be taken into account in future applications of apigenin for cancer therapy of men.Bingyuan WangMingrui ZhangJiankang GuoZhiguo LiuRong ZhouFei GuoKui LiYulian MuMDPI AGarticleapigeninspermatogonial proliferation<i>Prmt7</i><i>Akt3</i>mouseBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12209, p 12209 (2021)
institution DOAJ
collection DOAJ
language EN
topic apigenin
spermatogonial proliferation
<i>Prmt7</i>
<i>Akt3</i>
mouse
Biology (General)
QH301-705.5
Chemistry
QD1-999
spellingShingle apigenin
spermatogonial proliferation
<i>Prmt7</i>
<i>Akt3</i>
mouse
Biology (General)
QH301-705.5
Chemistry
QD1-999
Bingyuan Wang
Mingrui Zhang
Jiankang Guo
Zhiguo Liu
Rong Zhou
Fei Guo
Kui Li
Yulian Mu
The Effects of Flavonoid Apigenin on Male Reproductive Health: Inhibition of Spermatogonial Proliferation through Downregulation of <em>Prmt7</em>/<em>Akt3</em> Pathway
description Apigenin, a common dietary flavonoid abundantly present in a variety of fruits and vegetables, has promising anticancer properties. As an effector of apigenin in myoblasts, protein arginine methyltransferase 7 (<i>Prmt7</i>) is required for male germ cell development. However, whether apigenin may influence male reproductive health through <i>Prmt7</i> is still unclear. To this end, mouse spermatogonia were treated with different concentrations (2.5 to 50 μM) of apigenin for 48 h, which showed that apigenin could cause reduced cell proliferation in conjunction with longer S phase and G2/M phase (with concentrations of 10 and 20 μM, respectively), and increased apoptosis of spermatogonia (with concentration of 20 μM). Reduced <i>Prmt7</i> expression was found in 20 μM apigenin-treated spermatogonia. Moreover, siRNA-induced <i>Prmt7</i> knockdown exhibited similar influence on spermatogonia as that of apigenin treatment. In mechanistic terms, transcriptome analysis revealed 287 differentially expressed genes between <i>Prmt7</i>-downregulated and control spermatogonia. Furthermore, rescue experiments suggested that the effects of apigenin on spermatogonia might be mediated through the <i>Prmt7</i>/<i>Akt3</i> pathway. Overall, our study supports that apigenin can interfere with mouse spermatogonial proliferation by way of the downregulated <i>Prmt7</i>/<i>Akt3</i> pathway, which demonstrates that the concentration should be taken into account in future applications of apigenin for cancer therapy of men.
format article
author Bingyuan Wang
Mingrui Zhang
Jiankang Guo
Zhiguo Liu
Rong Zhou
Fei Guo
Kui Li
Yulian Mu
author_facet Bingyuan Wang
Mingrui Zhang
Jiankang Guo
Zhiguo Liu
Rong Zhou
Fei Guo
Kui Li
Yulian Mu
author_sort Bingyuan Wang
title The Effects of Flavonoid Apigenin on Male Reproductive Health: Inhibition of Spermatogonial Proliferation through Downregulation of <em>Prmt7</em>/<em>Akt3</em> Pathway
title_short The Effects of Flavonoid Apigenin on Male Reproductive Health: Inhibition of Spermatogonial Proliferation through Downregulation of <em>Prmt7</em>/<em>Akt3</em> Pathway
title_full The Effects of Flavonoid Apigenin on Male Reproductive Health: Inhibition of Spermatogonial Proliferation through Downregulation of <em>Prmt7</em>/<em>Akt3</em> Pathway
title_fullStr The Effects of Flavonoid Apigenin on Male Reproductive Health: Inhibition of Spermatogonial Proliferation through Downregulation of <em>Prmt7</em>/<em>Akt3</em> Pathway
title_full_unstemmed The Effects of Flavonoid Apigenin on Male Reproductive Health: Inhibition of Spermatogonial Proliferation through Downregulation of <em>Prmt7</em>/<em>Akt3</em> Pathway
title_sort effects of flavonoid apigenin on male reproductive health: inhibition of spermatogonial proliferation through downregulation of <em>prmt7</em>/<em>akt3</em> pathway
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/d435b2e721964d0f99bd1a340da5a1b4
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