It seems that in 1537 Charles V proposed that Infante Luís of Portugal, Duke of Beja (3 March 1506 – 27 November 1555), son of King Manuel I be married to Henry VIII of England's daughter, future Queen Mary I.
Luís had been considered a bright young prince and considered, at least in the letters "virtuous, valourous, and generous", having studied mathematics and astronomy. He had accompanied Charles V to Tunis, and it was proposed that he be given the Duchy of Milan, as a way of securing peace between France and the Holy Roman Empire. The French were agreeable to the scheme as it would also potentially bring a Catholic Prince to the throne of England.
It also seems that Henry VIII was in favour of marrying off the young princess on the condition that she renounce her place in the line of succession any future children he should have. The negotiations seemed to have almost come to fruition as Portugal and England maintained friendly relations throughout this period.
The question is, if a younger marriage would have allowed Mary to produce offspring. When she married Philip II, she was 37 and never produced any children. If she gets married at an earlier age, would a child be possible? Assuming that Portugal's throne becomes vacant in 1578 as IOTL, if a surviving heir is available would he or she be the heir to both Portugal and England resulting in a dynastic union? I would be curious to see what effects this would have had on Europe in the short-term, and even long-term.