Do Aging and Parity Affect VEGF-A/VEGFR Content and Signaling in the Ovary?—A Mouse Model Study
In this study, the effects of aging and parity on VEGF-A/VEGFR protein content and signaling in the mice ovaries were determined. The research group consisted of nulliparous (virgins, V) and multiparous (M) mice during late-reproductive (L, 9–12 months) and post-reproductive (P, 15–18 months) stages...
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MDPI AG
2023-02-01
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author | Valentina Di Nisio Gianna Rossi Alessandro Chiominto Ezio Pompili Sandra Cecconi |
author_facet | Valentina Di Nisio Gianna Rossi Alessandro Chiominto Ezio Pompili Sandra Cecconi |
author_sort | Valentina Di Nisio |
collection | DOAJ |
description | In this study, the effects of aging and parity on VEGF-A/VEGFR protein content and signaling in the mice ovaries were determined. The research group consisted of nulliparous (virgins, V) and multiparous (M) mice during late-reproductive (L, 9–12 months) and post-reproductive (P, 15–18 months) stages. Whilst ovarian VEGFR1 and VEGFR2 remained unchanged in all the experimental groups (LM, LV, PM, PV), protein content of VEGF-A and phosphorylated VEGFR2 significantly decreased only in PM ovaries. VEGF-A/VEGFR2-dependent activation of ERK1/2, p38, as well as protein content of cyclin D1, cyclin E1, and Cdc25A were then assessed. In ovaries of LV and LM, all of these downstream effectors were maintained at a comparable low/undetectable level. Conversely, the decrease recorded in PM ovaries did not occur in the PV group, in which the significant increase of kinases and cyclins, as well phosphorylation levels mirrored the trend of the pro-angiogenic markers. Altogether, the present results demonstrated that, in mice, ovarian VEGF-A/VEGFR2 protein content and downstream signaling can be modulated in an age- and parity-dependent manner. Moreover, the lowest levels of pro-angiogenic and cell cycle progression markers detected in PM mouse ovaries sustains the hypothesis that parity could exert a protective role by downregulating the protein content of key mediators of pathological angiogenesis. |
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id | doaj.art-7dd29f05346047c1bb463add34ea98cc |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-11T08:44:04Z |
publishDate | 2023-02-01 |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-7dd29f05346047c1bb463add34ea98cc2023-11-16T20:58:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244331810.3390/ijms24043318Do Aging and Parity Affect VEGF-A/VEGFR Content and Signaling in the Ovary?—A Mouse Model StudyValentina Di Nisio0Gianna Rossi1Alessandro Chiominto2Ezio Pompili3Sandra Cecconi4Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynecology, Karolinska Institutet and Karolinska University Hospital, 14186 Huddinge, SwedenDepartment of Life, Health and Environmental Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, ItalyDepartment of Pathology, San Salvatore Hospital, 67100 L’Aquila, ItalyDepartment of Pathology, San Salvatore Hospital, 67100 L’Aquila, ItalyDepartment of Life, Health and Environmental Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, ItalyIn this study, the effects of aging and parity on VEGF-A/VEGFR protein content and signaling in the mice ovaries were determined. The research group consisted of nulliparous (virgins, V) and multiparous (M) mice during late-reproductive (L, 9–12 months) and post-reproductive (P, 15–18 months) stages. Whilst ovarian VEGFR1 and VEGFR2 remained unchanged in all the experimental groups (LM, LV, PM, PV), protein content of VEGF-A and phosphorylated VEGFR2 significantly decreased only in PM ovaries. VEGF-A/VEGFR2-dependent activation of ERK1/2, p38, as well as protein content of cyclin D1, cyclin E1, and Cdc25A were then assessed. In ovaries of LV and LM, all of these downstream effectors were maintained at a comparable low/undetectable level. Conversely, the decrease recorded in PM ovaries did not occur in the PV group, in which the significant increase of kinases and cyclins, as well phosphorylation levels mirrored the trend of the pro-angiogenic markers. Altogether, the present results demonstrated that, in mice, ovarian VEGF-A/VEGFR2 protein content and downstream signaling can be modulated in an age- and parity-dependent manner. Moreover, the lowest levels of pro-angiogenic and cell cycle progression markers detected in PM mouse ovaries sustains the hypothesis that parity could exert a protective role by downregulating the protein content of key mediators of pathological angiogenesis.https://www.mdpi.com/1422-0067/24/4/3318VEGF-AVEGFR2agingovaryparity |
spellingShingle | Valentina Di Nisio Gianna Rossi Alessandro Chiominto Ezio Pompili Sandra Cecconi Do Aging and Parity Affect VEGF-A/VEGFR Content and Signaling in the Ovary?—A Mouse Model Study International Journal of Molecular Sciences VEGF-A VEGFR2 aging ovary parity |
title | Do Aging and Parity Affect VEGF-A/VEGFR Content and Signaling in the Ovary?—A Mouse Model Study |
title_full | Do Aging and Parity Affect VEGF-A/VEGFR Content and Signaling in the Ovary?—A Mouse Model Study |
title_fullStr | Do Aging and Parity Affect VEGF-A/VEGFR Content and Signaling in the Ovary?—A Mouse Model Study |
title_full_unstemmed | Do Aging and Parity Affect VEGF-A/VEGFR Content and Signaling in the Ovary?—A Mouse Model Study |
title_short | Do Aging and Parity Affect VEGF-A/VEGFR Content and Signaling in the Ovary?—A Mouse Model Study |
title_sort | do aging and parity affect vegf a vegfr content and signaling in the ovary a mouse model study |
topic | VEGF-A VEGFR2 aging ovary parity |
url | https://www.mdpi.com/1422-0067/24/4/3318 |
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