Italian Prime Minister Matteo Renzi's defeat in a referendum over his plan to reform the constitution is a harbinger of further uncertainty in Europe next year where populist parties are making gains in the key economies of France, Germany and the Netherlands.

On Sunday, Renzi said he would resign following a "clear" rejection of legislative reform measures as what was originally a rather dry referendum on constitutional change turned into a high-stakes game with the political and economic stability of Italy—and ultimately the euro zone—at risk.

"We know that the referendum was technically on constitutional reforms but the Italian government linked the vote to its own political future," said Stratfor's senior European analyst, Adriano Bosoni.

Sunday's vote was on whether the country's second chamber should be stripped of some of its powers. The country's government is hamstrung by procedure and delays to legislation. A "yes" vote in the referendum would have meant that laws would only need the approval of the lower house to be passed.

Renzi had pinned his political future on the vote, saying he would resign if a "yes" vote was rejected.