Democratic presidential candidates Hillary Rodham Clinton and Bernie Sanders wave after a candidates’ forum at Winthrop University in Rock Hill, S.C., on Nov. 6. (Chris Keane/Reuters)

As the Democratic presidential candidates prepare for their second debate next weekend, a disputed moment of alleged sexism from the first exchange has come to symbolize a sharper and more personal confrontation between Hillary Rodham Clinton and her chief rival, Sen. Bernie Sanders.

The topic was gun control, the issue her campaign considers the keenest policy difference between Clinton and Sanders, and perhaps the only one on which he is positioned to her right. But it was Clinton’s suggestion, after the fact, that the senator from Vermont had spoken to her in a patronizing and dismissive way by accusing her of shouting that has added an edge to an almost painfully polite primary contest.

The episode provides one of the clearest examples of how the Democratic front-runner — who largely avoided such issues in her previous presidential run — plans to make gender and her experiences in the male-dominated realm of national politics a centerpiece of her 2016 bid. But the focus on the Sanders remark, which could easily be taken as harmless or ham-fisted at worst, raises the risk that Clinton may come off as thin-skinned or too politically correct.

Sanders has denied that he had any sexist intent behind the comment, and Clinton has not directly accused him of such. Even so, her references since the exchange to the ways that people hear and react to women are clearly a subtle cue to female voters.

Clinton has “mischaracterized” his remarks on guns, Sanders said during a candidate forum Friday in South Carolina, suggesting that she has twisted the exchange for her own ends.

Clinton is making her experiences as a woman a centerpiece of her presidential campaign. (Chris Keane/Reuters)

Sanders’s wife made that charge more explicitly in an interview last week. Any suggestion that her husband is sexist “is completely ludicrous, as every woman who’s ever worked for him and known him knows,” Jane O’Meara Sanders said.

“I think that’s a misrepresentation of what he said, and I think they know that,” she said. “I also think it diminishes the fact that many, many women have been victims of sexism, so why are you calling it out when it’s not there and you know it? That’s not okay.”

In the first candidates’ debate, Oct. 13 in Las Vegas, Clinton argued in favor of tougher firearm laws and accused Sanders of siding with the gun lobby. With a look of annoyance, Sanders replied, “All the shouting in the world is not going to do what I would hope all of us want, and that is keep guns out of the hands of people who should not have those guns.”

Clinton and her allies have since characterized the comment as tone-deaf sexism. “When women talk,” Clinton told a crowd at a women’s forum in Washington, “some people think we’re shouting.”

The subject and Clinton’s knowing tone were meant to resonate with women who say they are evaluated by a sexist standard that expects them to be mild-mannered or deferential. Some Clinton allies also have complained that a joke from Sanders’s campaign manager about considering her as a running mate was patronizing.

New criticism

Until recently, Clinton mostly refrained from criticizing Sanders, even as his insurgent candidacy took off and posed a more potent threat than expected.

“She feels passionate about the issue of gun violence, and she’s going to continue to give voice and expression to the view she’s heard across the country, particularly [from] moms who have lost their children,” Clinton communications director Jennifer Palmieri said.

Sanders has denied that his “shouting” comment at the first debate had any sexist intent behind it or that it was directed at Clinton. (Chris Thelen/AP)

There is a clear gender gap on the issue. An October Washington Post-ABC News poll found that women were 16 percentage points more likely to say gun violence is a “very serious” problem andwere more likely to favor enacting new gun restrictions. The 2014 General Social Survey found that 35 percent of men report owning a gun, compared with 12 percent of women.

Sanders has fended off the suggestion of sexism from Clinton and her boosters by noting that he had talked about “shouting” and gun control for weeks before he confronted Clinton at the debate. Some Sanders supporters say it is a stretch for Clinton to make the case that the line was directed at her.

But Palmieri said, “Throughout her life, Hillary Clinton has been a fighter for causes that most affect children and families, and she isn’t about to modulate her advocacy on these issues now.”

The sexism charge is a preview of the kind of accusations Clinton and her allies seem likely to make against the eventual Republican presidential nominee. If Clinton wins the Democratic nod, her Republican opponent will probably be a man.

Clinton has repeatedly accused the large GOP field — all men, except for former technology executive Carly Fiorina — of ignoring or overriding women’s health concerns and reproductive rights by attacking Planned Parenthood. Her defense of the organization over the summer against charges of improper handling of tissue from aborted fetuses was an unmistakable signal that she would target her appeals directly to female voters.

When she first delivered her line about women and shouting at an Oct. 23 women’s forum in Washington, it received loud cheers, laughter and applause from the largely female audience.

“It’s sometimes hard to believe, but the notion that women should be equal partners in the life of our nation is still pretty new,” Clinton said at the event, where Sanders also spoke. “I’m doing everything I can to make sure the issues that matter most to women and families are front and center in this race.” She has repeated the same line several times since, but it has not resonated as deeply.

Clinton has focused on equal pay, better child-care and family-leave policies, and other issues particularly important to women, and she talks frequently about her experience as a working mother. The emphasis differs markedly from that of her unsuccessful 2008 campaign, when she played down her gender in favor of her credentials.

At a town hall meeting Saturday in Orangeburg, S.C., highlighting issues important to African American voters, one of the first questions Clinton received was from a young woman who asked how companies should be held accountable for pay disparities and how women can ensure that they are being paid the same amount as men for the same work.

Clinton answered with a simple: “Amen.”

“I cannot do a town hall anywhere in America without being asked this question,” she said to applause. “And for all those Republicans who say this is not a real-world problem, I wish they could come to my town halls.”

“This is not just a women’s issue, this is a family issue, this is an economic issue,” Clinton said.

Sanders on defense

Sanders appeared Saturday in Rock Hill, S.C., at a regional meeting of a group that seeks to elect more women to office; he argued that the economic issues on which he has built his campaign are “intricately connected” to the advancement of women.

Sanders — a self-described democratic socialist — said that raising the minimum wage to $15 an hour, for example, would help millions of single mothers, as would making child care more affordable and mandating that employers provide three months of paid family leave after a woman has a child.

After Sanders campaign manager Jeff Weaver was quoted by Bloomberg Politics as saying that Clinton would “make a great vice president,” Stephanie Schriock, president of Emily’s List, a group that promotes female candidates, quickly took to Twitter to call the remarks a “condescending insult by a team who knows better.” Other Clinton allies have noted that Sanders’s senior campaign staff is overwhelmingly male and white.

Sanders has appeared ruffled and annoyed when asked about the suggestion that he and his team are insensitive or blind to women’s concerns. In an interview with MSNBC last week, he cited his “pro-woman voting record” and pointed out that he had used the “shouting” line before. “That’s what I’ve been saying for months, and I think the record will demonstrate that,” he said.

He added, however, that his campaign manager’s remarks were “inappropriate.”

Two days later, Sanders told reporters that the back-and-forth over sexism had gotten too personal, and “that is unfortunate.”

Fifteen years ago, as Clinton was running for the Senate from New York, her team seized on a moment in a debate with her Republican rival, Rick Lazio, that many considered demeaning, when he strode across the stage and wagged his finger at her.

In a March interview with Mother Jones, Lazio warned that Republicans who aim to beat Clinton this cycle should learn from his experience. if her campaign “can connect with women who have faced sexism, he said, “this is going to be one of the tactics to put the Republican [nominee] on defense.”

Scott Clement in Washington and Abby Phillip in Orangeburg, S.C., contributed to this report.