His siblings included Ippolito II, Archbishop of Milan and later Cardinal, nun Leonora, and Francesco, Marchese di Massalombarda.

They sought to make a deal with Ercole, who subsequently provided the army with the necessary artillery to later advance on and sack the city of Rome.

Thus the court she assembled about her in Ferrara corresponded to the tradition which the cultivation of science and art implicitly required, including scholars like Bernardo Tasso and Fulvio Pellegrini Morato.

Meanwhile, Duchess Renée was corresponding with a number of Protestants and was suspected to have converted, despite the presence of a special court of the Inquisition in Ferrara.

Ercole brought accusations of heresy against his wife to King Henry II of France and Inquisitor Oriz in 1554, and she subsequently confessed.