VEGFR2 Expression Is Differently Modulated by Parity and Nulliparity in Mouse Ovary.

Valentina Di Nisio,Gian Mario Tiboni,Sandra Cecconi,Gianna Rossi,Roberto Iorio,Guido Macchiarelli,Sabrina Petricca,Cristina Pellegrini

doi:10.1155/2018/6319414

Valentina Di Nisio, Gian Mario Tiboni + Show 6 more

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https://doi.org/10.1155/2018/6319414

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Abstract

Parity and nulliparity exert opposite effects on women's health, as parity is considered a protective factor for several reproductive diseases. This study is aimed at determining if ovarian VEGF and VEGFR2 expression are differently modulated in the ovaries of parous and nulliparous mice. To this end primiparous and nulliparous fertile mice were sacrificed at postovulatory stage. Whole ovaries, corpus luteum, and residual stromal tissues were analyzed to assess VEGF/VEGFR2 expression levels. Ovarian mRNA amounts of Vegfa (120 and 164) and Vegfr2 were comparable between primiparous and nulliparous mice; both isoforms and receptor were accumulated mainly in corpus luteum tissues. VEGF 120 and 164 protein accumulation and distribution mirrored that of mRNA. Conversely, VEGFR2 protein content was significantly higher in ovaries of nulliparous mice and was more efficiently phosphorylated in ovaries of primiparous mice. In both groups, VEGFR2 was preferentially expressed in corpus luteum, while its phosphorylated form was equally distributed in two somatic compartments. We suggest that parity influences VEGFR2/phospho-VEGFR2 expression and tissue distribution. This difference could be part of a more complex mechanism that at least in mice is activated after the first pregnancy and likely aims to preserve female health.

Highlights

A significant decline of fertility rate is occurring in developed countries, mainly due to economic problems and lifestyle choices
The present study explored how pregnancy can exert its protective effects by assessing if vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor type 2 (VEGFR2) expression were differently modulated in the ovaries of adult primiparous, compared with nulliparous mice
The chemicals used were purchased from the following sources: rabbit polyclonal VEGFA and phospho-ERK1/2 (Thr202/Tyr204; sc-16982-R); mouse monoclonal Flk1, ERK1/2, and α/β tubulin; goat anti-rabbit IgG conjugated to horseradish peroxidase (HRP) and goat anti-mouse IgG conjugated to HRP from Santa Cruz Biotechnology (Santa Cruz, CA, USA)

Summary

Introduction

A significant decline of fertility rate is occurring in developed countries, mainly due to economic problems and lifestyle choices. Young women can experience fertility problems because of several pathological conditions affecting the ovary, first of all cancer [3,4,5], thereby increasing the number of childless women. In women undergoing stimulation protocols during IVF procedures the question is still debated [11, 12] All these diseases are characterized at the molecular level by elevated hypoxia and overexpression of proangiogenic factors, especially vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor type 2 (VEGFR2) [8, 13,14,15]. This is not surprising, as in the adult mammalian ovary a delicate balancing of pro/antiangiogenic factors participates in the physiological modulation of cyclical angiogenesis and vascular regression [8, 16,17,18,19]

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