DO NULLIPARITY AND MENOPAUSE MODULATE THE EXPRESSION LEVELS OF MAIN PRO-ANGIOGENIC FACTORS: VEGF, VEGFR2, AKT AND ERK2, IN THE MOUSE OVARY?

Objective: Nulliparity and menopause are considered risk factors for ovarian cancer. Nulliparity represents a condition capable of affecting the expression levels of the pro-angiogenic factors and modulating the degree of phosphorylation of signals involved in endothelial cell proliferation. This experimental animal study involved a total of 40 CD1 female mice, young (4-months-old) and old (15-months-old), both parous and nulliparous, where the expression levels of VEGF, VEGFR2, ERK2, Akt and PTEN proteins were determined. Methods: Mice, called Mothers (M), were mated and sacrificed after the first pregnancy and lactation (Young, Y, n = 10) or at 15 month (Old, O, n = 10) of age, when they’re in menopause. The same protocol was adopted for the group of nulliparous mice, called Virgins (V), sacrificed without mating either young (YV, n = 10) or old (OV, n=10). Ovaries were collected and stored for Western blot analysis. The expression levels of VEGF, VEGFR2, ERK2, Akt and PTEN proteins were determined into the 4 groups. Results: VEGF content was always higher in V than in M, but no age-dependent increase of VEGF was recorded in V because of the high levels already present in the YV. VEGFR2 content was higher in V than in M, and was accumulated in OV. Akt and ERK2 were phosphorylated more efficiently in V than in M. PTEN was under phosphorylated in OV. Conclusion: The finding that in the ovaries of nulliparous (V) mice the expression levels of pro-angiogenic proteins are enhanced in comparison to parous (M) mice, contributes to explain epidemiological data by providing the first molecular explanation of the protective role of pregnancy on female health; the over-expression of specific pro-angiogenic proteins and their over-activity can contribute to explain the reason why the incidence of ovarian cancer in nulliparous women is higher than in parous ones.