A Fox News interview from 2021, in which Sen. JD Vance smeared Vice President Kamala Harris as one of a group of "childless cat ladies," has resurfaced since he became the Republican vice presidential nominee, sparking widespread anger.

In the clip, Vance questioned Democrats -- including Harris, Transportation Secretary Pete Buttigieg and U.S. Rep. Alexandria Ocasio-Cortez -- for not having biological children.

"We are effectively run in this country via the Democrats, via our corporate oligarchs, by a bunch of childless cat ladies who are miserable at their own lives and the choices that they've made and so they want to make the rest of the country miserable too," Vance said.

"How does it make any sense that we've turned our country over to people who don't really have a direct stake in it?" he asked.

The 2021 interview began circulating widely after Hillary Clinton shared the clip on X. "What a normal, relatable guy who certainly doesn't hate women having freedoms," she wrote.

Though Harris does not have biological children, she does have two stepchildren -- Cole and Ella Emhoff -- who have lovingly referred to her as "Momala."

Kerstin Emhoff -- second gentleman Doug Emhoff's ex-wife, and mother to Cole and Ella Emhoff -- has been a vocal supporter of Harris, and defended her against attacks about her parental status.

"These are baseless attacks. For over 10 years, since Cole and Ella were teenagers, Kamala has been a co-parent with Doug and I," she said. "She is loving, nurturing, fiercely protective, and always present. I love our blended family and am grateful to have her in it."

Ella Emhoff shared her mother's statement on Instagram, writing, "I love my three parents."

"How can you be 'childless' when you have cutie pie kids like Cole and I?" she added.

Buttigieg also hit back against Vance's comments, saying in a CNN interview that Vance should not speak about other people's children.

"The really sad thing is he said that after Chasten and I had been through a fairly heartbreaking setback in our adoption journey," Buttigieg said. "He couldn't have known that, but maybe that's why you shouldn't be talking about other people's children, and it's not about his kids or my kids or the vice president's family. It's about your family, people's families whose well-being will depend on whether we go into a future led by somebody like Kamala Harris, who is focused on expanding the prosperity, the freedom, the well-being of our families."

Actress Jennifer Aniston, who has spoken about her struggles with fertility, made a post on Instagram slamming Vance, who has voted against establishing federal protections for in vitro fertilization.

"I truly can't believe this is coming from a potential VP of The United States," Aniston wrote. "All I can say is ... Mr Vance, I pray that your daughter is fortunate enough to bear children of her own one day. I hope she will not need to turn to IVF as a second option. Because you are trying to take that away from her too."

In a post on X, former President Donald Trump's national press secretary Karoline Leavitt said Vance's words had been taken out of context and that he was being "unfairly attacked."

"As a new mom, my heart aches for women who are unable to bear children," Leavitt wrote, before sharing a 30-second video of Vance speaking at an Intercollegiate Studies Institute event on July 24, 2021 -- in which Vance similarly attacked "the childless left" but added a caveat that his attacks are not directed at those who are "unable" to have kids.

Vance's spokesperson Taylor Van Kirk said the Senator's words had been "twisted."

"Once again, the leftwing media have twisted Senator Vance's words and spun up a false narrative about his position on the issues," Van Kirk said. "The only childlessness we should be talking about are the childless parents who lost their kids to the murderous thugs and deadly fentanyl coming across Kamala's southern border."

Vance's comments have even struck a nerve with some prominent conservative women.

"One of my best friends did rounds and rounds of unsuccessful IVF wanting to have a child. It is still painful to talk about," Meghan McCain said in an X post. "This 'childless women' comment by JD Vance has made so many waves with so many different friends of mine for its insensitivity and cruelty to women."

Beverly Hallberg, a fellow with the conservative nonprofit Independent Women's Forum, replied to McCain's post.

"I'm childless on earth, but I have a baby in heaven due to an ectopic pregnancy," Hallberg said. "Not all women who don't have children are childless by choice. It adds insult to injury, to put it mildly, when these comments are said."

Corie Whalen, media relations director at a Republican think tank and former congressional staffer, said on X she was disgusted by Vance's comments.

"I'm a right-leaning woman who agrees with almost nothing the Biden-Harris administration has done, but the primal hatred and disgust Vance stokes in me transcends politics," she wrote. "I suspect I am not the only woman of my vintage, so to speak, who feels this way."

The head of a major infertility nonprofit also spoke out against Vance, calling his comments "painful and tone-deaf."

"People are childfree for many reasons -- from grieving the pain of miscarriage to experiencing failed adoptions or rounds of fertility treatments to making their own choice not to have children," said Barbara Collura, president and CEO of RESOLVE: The National Infertility Association.

"For some, living without children doesn't feel like a choice that they made, but a choice that they live with, despite trying to grow their families," Collura added. "Under no circumstances, should living childfree be weaponized in a way that degrades people or their value to society."

In an interview with ABC News at the American Teachers Federation Conference in Houston, Briget Rein -- a former Brooklyn teacher, who wore a pink shirt that said "Cats Against Trump" -- proudly identified herself as a "cat lady" and said she thought Vance's remarks were "stupid."

"Vance also is unprepared to be a vice president, he's not prepared. Because he's busy looking at the surface. He's not looking at the full picture," she said."You know, this cat lady went to college. This cat lady went to work ... but he's busy talking about cat ladies, and talking about women in a very derogatory fashion."

Sen. Kirsten Gillibrand, D-N.Y., argued that even small attacks on Harris -- even if Harris and her campaign embrace the incoming and try to make light of it -- could undermine her, pointing to the 2021 video of the comments from Vance.

"It's really undermining her, and the fact that we get fixated on it and repeat it, and even though we just do memes and try to make it funny, we're literally talking about that she's a cat owner," Gillibrand said Wednesday night after a screening of a documentary on Geraldine Ferraro. "It's absurd. She's running for president the United States."

ABC News' Brittany Shepherd contributed to this report.