Republican hopes of winning back the Senate majority in next year’s midterms are increasingly being challenged by a wave of retirements.

Sen. Roy Blunt (Mo.) on Monday became the fifth GOP incumbent to announce he won’t seek reelection in 2022. Blunt’s seat is relatively safe for Republicans, but the two-term senator’s retirement creates yet another line of defense for the GOP as it seeks to defend open seats created by Republican retirements in Ohio, Pennsylvania, North Carolina and Alabama. In all, Republicans are defending 20 seats compared with Democrats’ 14.

That creates plenty of openings for Democrats to add to their majority even in a midterm election, when the president’s party typically loses seats.

To be sure, Republicans appear more likely than not to keep the open seats in Alabama and Missouri, a former battleground that has shifted sharply to the right in recent years. Even Ohio, a longtime swing state, will pose a challenge for Democrats. Former President Trump won the state comfortably in both 2016 and 2020, and Sen. Sherrod Brown (Ohio) stands as the last-remaining Democrat elected to statewide office.

But the GOP will also be defending seats in Wisconsin and Pennsylvania, two states President Biden narrowly won in the presidential race, as well as the swing states of North Carolina and Florida. The most vulnerable incumbents that Democrats are defending are first-term senators in Arizona and Georgia, which went blue in 2020 for the first time in decades and where the GOP will seek to go on offense.

Even in historically red states, the spate of retirements means that Republicans may have to contend with bruising primary fights that could weaken their standing ahead of competitive general elections.

“I think the more immediate question, in part because this will happen first is, what will happen in primaries and what candidates emerge from that?” veteran Republican strategist Doug Heye told The Hill.

The retirements also mark the latest sign of an ongoing shift in the GOP away from the traditional conservatism that has defined it for the past several decades. With seasoned Republican lawmakers stepping down, Trump loyalists are enthusiastically eyeing their seats as they look to solidify the former president’s ideological grip on the party.

There’s already a GOP primary fight underway in Ohio, where former state Treasurer Josh Mandel and former state Republican Party chair Jane Timken are vying to take up Trump’s mantle in the race to replace retiring Sen. Rob Portman. In Alabama, Rep. Mo Brooks (R-Ala.), a staunch Trump ally, has expressed interest in running for Sen. Richard Shelby’s seat.

Meanwhile, Trump’s daughter-in-law Lara Trump is said to be weighing a bid to replace retiring Sen. Richard Burr (R) in North Carolina.

Also looming over the Senate retirements, and adding to consternation within the GOP, is Trump’s pledge to oust Republican lawmakers whom he views as insufficiently loyal to his vision for the party.

The former president vowed recently to travel to Alaska to campaign against Sen. Lisa Murkowski (R) in her 2022 reelection bid. Murkowski was one of seven senators to vote to convict Trump in his impeachment trial last month and is the only one of that cohort up for reelection next year. Trump has also already thrown his support behind a primary challenge to Rep. Anthony Gonzalez (Ohio), who was among 10 House Republicans who voted to impeach him in January.

There’s an ongoing debate among Republicans over exactly what role Trump should play in the party’s politics in 2022 and beyond. While some Republicans have blamed Trump for recent electoral losses and have expressed a desire to put his presidency behind them, others argue that the former president remains the GOP’s most effective campaigner and influential figure.

“Donald Trump is going to do whatever he feels best helps him, so helping other candidates is at the bottom of his priority list,” Heye said.

There are also signs of tension between Trump and the GOP’s political committees that could complicate life for candidates. On Monday, the former president called on donors to contribute to his Save America PAC instead of the Republican National Committee (RNC) or the GOP’s other campaign groups. The statement came after Trump’s lawyers demanded that the RNC, the National Republican Senatorial Committee and the National Republican Congressional Committee stop using his name and likeness for fundraising and merchandise sales.

More retirements could be on the horizon. Two other GOP senators, Chuck Grassley (Iowa) and Ron Johnson (Wis.), have not yet committed to running for reelection in 2022. Johnson, who previously pledged to not seek a third term in the Senate but is still considering a reelection bid, said last week that retiring after his current term is “probably my preference now.” Grassley, who will be 89 years old on Election Day in 2022, has said he will decide this fall whether to run.

Democrats are particularly eager to compete for Johnson’s seat in Wisconsin, given a spate of high-profile Democratic victories there in recent years that included Biden’s win in November.

Former North Carolina Gov. Pat McCrory (R), who’s strongly considering a bid for Burr’s open seat next year, said that growing anti-establishment sentiment among activists on both sides of the aisle have contributed to the recent retirements. Voters still value political experience, he said, but are increasingly enthusiastic about D.C. outsiders.

“It’s becoming harder to defend incumbency than to say you got new ideas from outside D.C.,” McCrory said. “The days of staying so long are past due. You do need some experience. You don’t want it all to happen at once, but rotation is good.”

“It might be a great opportunity to bring in new blood with experience outside of D.C. A former mayor or a former governor or otherwise,” he added. Before McCrory became the North Carolina governor, he served as the mayor of Charlotte for 14 years.

The Democratic performance at the Senate level in 2022 will likely hinge on Biden’s popularity in the midterms. Most first-term presidents in modern history have lost seats in Congress during their first midterms.

But Democrats aren’t writing off even hard-to-win open seats. While Republicans have projected confidence that they will hold Blunt’s seat in Missouri, Sen. Gary Peters (D-Mich.), chairman of the Democratic Senatorial Campaign Committee (DSCC), said Monday that his group would be keeping an eye on the Missouri Senate race, adding that there are “a number of well-qualified folks who are interested in running.”

“Biden has started off very strongly, but the national winds frequently influence what happens in the individual states in the midterm elections,” said Michael Gordon, Democratic strategist and principal at Group Gordon.

“If he can remain popular and people can believe that he is taking the country forward in a new direction, then it is more likely that Democrats can pick up some of these open Senate seats,” he added.