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...

Full description

Bibliographic Details
Main Authors: Valentina Di Nisio, Gianna Rossi, Alessandro Chiominto, Ezio Pompili, Sandra Cecconi
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/4/3318
_version_ 1797620543347752960
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.
first_indexed 2024-03-11T08:44:04Z
format Article
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
publisher MDPI AG
record_format Article
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
work_keys_str_mv AT valentinadinisio doagingandparityaffectvegfavegfrcontentandsignalingintheovaryamousemodelstudy
AT giannarossi doagingandparityaffectvegfavegfrcontentandsignalingintheovaryamousemodelstudy
AT alessandrochiominto doagingandparityaffectvegfavegfrcontentandsignalingintheovaryamousemodelstudy
AT eziopompili doagingandparityaffectvegfavegfrcontentandsignalingintheovaryamousemodelstudy
AT sandracecconi doagingandparityaffectvegfavegfrcontentandsignalingintheovaryamousemodelstudy