When the history books are written, this week may go down as a seminal point in the 2012 battle for control of the Senate.

Despite a multitude of vulnerable Democratic-held seats at the start of the cycle, it’s increasingly possible that Republicans’ inability to stem their own losses could allow Democrats to hold their narrow majority.

Sen. Olympia Snowe’s (R-Maine) retirement immediately put an otherwise safe seat in jeopardy. Now, GOP-held seats in Maine, Massachusetts and Nevada — three states President Barack Obama won by 12 points or more — are in critical political peril, making the party’s task of netting four seats more difficult.

Further complicating the GOP’s path to 51 seats was former Nebraska Sen. Bob Kerrey’s (D) announcement that he will run to succeed retiring Sen. Ben Nelson (D). The Nebraska seat is still a tough hold for Democrats, but Kerrey is the one recruit who can keep it in play for the party, which could, at the very least, force national Republicans to expend valuable resources.

On Wednesday, one day after Snowe’s announcement, Republican strategists were noticeably unenthusiastic to discuss the Senate landscape and the increasingly complicated arithmetic needed for a majority. It was just the opposite for Democrats, some of whom said they could even foresee the party holding not only the majority, but its current 53-47 seat margin.

“At this point, you can make a reasonable case for no change and you can make a reasonable case for a Democratic gain,” Democratic pollster Mark Mellman said. “Nobody thought that at the beginning of the cycle.”

Democrats can negate potential losses in, say, Missouri and North Dakota by winning the two GOP-held states in New England — Maine and Massachusetts — which is hardly a long-shot at this point. Leaving off another potential Democratic pickup in Nevada, that means Republicans would still need to win four more Democratic seats; the most likely targets are Nebraska, Montana and Virginia, along with Wisconsin or New Mexico.

That is still doable, and the Republican target list remains long and even includes Hawaii. But the chips would continue to stack up against the GOP if Sen. Jon Kyl’s (R) open seat in Arizona gets more competitive, which Democrats believe will happen when former Surgeon General Richard Carmona increases his name identification. He will have a tough race against Rep. Jeff Flake, who is expected to emerge from the GOP primary.

National Republican Senatorial Committee Chairman John Cornyn (Texas) attempted Wednesday to put a positive spin on a rough week. The Snowe and Kerrey news had the immediate effect of transforming two sure victories into competitive races, but Cornyn insisted that neither development would dramatically alter the playing field and were merely minor and temporary setbacks.

“Clearly this is a bump in the road, but I don’t think it changes the overall landscape,” Cornyn told reporters, adding that he expects Republicans to win in both states in November.

But the GOP’s path now relies on the party’s ability to win states Obama is targeting. Republican strategist Dan Judy said that puts the onus on the eventual Republican presidential nominee to win while carrying swing states such as Virginia, Wisconsin, Florida, New Mexico and Ohio — all of which Democrats are defending in the Senate.

“I think a majority is still possible, but the road to 51 is much tougher today, and much more dependent on a strong showing by the presidential nominee at the top of the ticket,” Judy said. “But if Obama wins re-election, it’s much more unlikely — although not impossible — that the Republicans will be able to win enough of those to take the Senate.”

Democratic Senatorial Campaign Committee Chairwoman Patty Murray (Wash.) said on MSNBC’s “Andrea Mitchell Reports” that she was “very excited” about Kerrey’s candidacy and called the open seat in Maine “a great opportunity.”

The GOP candidate field in Nebraska is set, and a viable nominee should emerge from the May 15 primary between Attorney General Jon Bruning, state Treasurer Don Stenberg and state Sen. Deb Fischer. That leaves five months for the nominee to run a competitive campaign in a strongly Republican state.

But Snowe’s retirement caught Republicans off guard, and Cornyn conceded that the NRSC is still assessing the political environment in Maine and the potential list of GOP candidates. With a March 15 filing deadline, Republicans don’t have much time to recruit a strong successor to Snowe, if one exists. Democratic Reps. Chellie Pingree and Mike Michaud have already taken steps toward running.

Sen. Jim DeMint (R-S.C.) and other Republicans were not immediately as buoyant about their prospects of holding the seat as Cornyn was, with a few acknowledging that it would make it harder for the GOP to win the Senate majority.

“I think it is a blow,” DeMint said.

The South Carolinian, who is active in endorsing and financially supporting candidates through his Senate Conservatives Fund political action committee, said he would also examine whether to get involved in Maine’s June 12 GOP primary. He noted that time was short and said he had not previously paid attention to Maine because he expected Snowe would run for re-election and easily hold the seat.

In 2010, Republicans captured the governor’s mansion in Maine and took control of both chambers of the state Legislature.

Snowe and Sen. Susan Collins (R) have represented the state for years, even as it grew more liberal with the rest of New England. Collins, during a brief interview Wednesday, agreed with Cornyn’s optimism, contending that while the seat is no longer the “sure bet” that it was for the GOP, it is still very winnable.

Senate Republican Conference Chairman John Thune (S.D.) argued that flipping the chamber was already a “heavy lift” before Snowe’s retirement.

“Obviously, we don’t know exactly what the candidates may be yet,” Thune said. “But we’re hoping that we’ll have a good one.”