"If it's a legitimate rape, the female body has ways to try to shut that whole thing down," he said.
Within hours, many women's groups had denounced his statement, as did McCaskill and GOP presidential candidate Mitt Romney.
Akin, 65, a six-term congressman from the St. Louis area, has apologized repeatedly for the remark and said he misspoke.
He reiterated Wednesday that no rape is legitimate, calling it a "heinous crime," and said he was misinformed about a rape victim's ability to ward off pregnancy.
"The fact of the matter is I think that anybody doing a lot of public speaking can make a mistake," he said. "They knew I wasn't perfect."
By staying in the race past an informal 5 p.m. deadline Tuesday, Akin made any future decision to back out of the race more complicated. If he steps down now, a court would have to certify his decision, and his campaign, or the state Republican Party, might be liable for the cost of reprinting ballots.
That could run into the hundreds of thousands of dollars, election officials said.
But Akin said he didn't feel alone in his ongoing battle against McCaskill. "That was a decision made by the citizens of our state and not politicians," he said on TV.
Akin said the race is not about him or his ego. "It is about the voters of the state of Missouri," he said. "They've chosen me because of the principles I stand on."
Still, many Republicans said privately Wednesday that Akin remained isolated with only two close advisers: his wife, Lulli, and his son, who's serving as campaign manager.
Many of those Republicans speculated about an array of possible scenarios to replace Akin that would allow him to step down and still save face, including a swap with a current member of Congress that would allow him to remain in the U.S. House, representing his St. Louis area district.
Republican insiders said that members of the party's state committee, which would pick a Senate replacement if Akin drops out, have been getting calls from potential candidates, as well as their allies pushing their case.
Few Republicans would speak on the record about the behind-the-scenes political chess game. But Akin would have to agree to end his Senate candidacy, which he continues to adamantly insist won't happen.
If a deal were to be worked out, the 60-some member state committee would have to sign off on a new Senate candidate. And a congressional committee would have to agree to Akin. Pulling off a pair of moves like that could be tricky, insiders said.
In fact, one GOP operative, Jeff Roe, called such speculation "preposterous."
Still, the talk continued throughout Wednesday on Twitter and several blogs. Other names mentioned for possible job swaps included U.S. Rep. Jo Ann Emerson, U.S. Rep. Blaine Luetkemeyer and Ann Wagner, the Republican candidate seeking to replace Akin in the 2nd Congressional District.
Emerson, of southeast Missouri, is generally viewed as a political moderate inside a party that has moved rightward and who could have trouble winning a statewide Republican primary where conservatives dominate. But she could possibly do better in a general election.
Some Republicans also mentioned St. Louis businessman John Brunner, who finished second in the Aug. 7 Republican primary. But critics noted Brunner spent about $8 million of his own money on that race against Akin and former state Treasurer Sarah Steelman of Rolla and still couldn't win the nomination. Steelman also was believed to be lobbying to replace Akin if he withdraws.
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