In his Quaestiones in Genesim, that great Spanish composer of Marian literature, St. Isidore of Seville (d. 636) gives a marvelous exegesis of Genesis 3:15:
The seed of the devil is a perverse suggestion; the seed of the woman is the fruit of a good work, by which the perverse suggestion of the devil is resisted. She will tread upon his head, because from the beginning she expels his perverse suggestions from her mind. He will strike at her heel, because until the end he will try to deceive her mind, which he was unable to deceive with his first suggestion. Some have understood the following expression in reference to the Virgin, from whom the Lord was born: "I will put enmity between you and the woman," since it was promised that the Savior was going to be born from her, in order to defeat the enemy and to destroy death, of which the enemy was the author. For they also understand the following as a reference to the fruit of Mary’s womb; namely, Christ: "She will tread upon your head, and you will strike at her heel." This means: You will attack him to kill him, but he (Christ), after you have been defeated, will rise again and tread upon your head which is death (19).
We see here in this exegesis the intimate union between the woman and her seed. Mary’s fiat at the Annunciation leads to the birth of the Savior, the one who "will rise again and tread upon … death." Mary’s fiat wasn’t just a "yes" to the Annunciation, but rather also a "yes" to the death of her Son on the Cross, where Mary would also be crucified spiritually and a sword would pierce her heart as well. The Church Fathers, in seeing Mary as the "woman" of Genesis 3:15, unearth the seed for the doctrine of Mary as Co-redemptrix and Mediatrix of All Graces. Co-redemptrix because she actively participates in the crushing of Satan’s head, and Mediatrix of All Graces because she mediated Christ into the world, who is the source of all grace. Nobody sums this doctrine up in relation to Genesis 3:15 better than that great master of Scripture, St. Jerome when he states: "Death came through Eve; life through Mary" (20).
(19) Quaestiones in Genesim 5, 5-7, quoted in Luigi Gambero. Mary and the Fathers of the Church, 378.
(20) Epistle 22, 21, trans. Charles Christopher Mierow, in Ancient Christian Writers, No. 33 (New York, NY: Newman Press, 1963), 154.