"How can we proclaim Christ to a generation that is changing? We must be careful not to administer a vaccine against faith to them," Francis told around 120 leaders of male religious orders during a meeting at the Vatican.
"I remember the case of a very sad little girl who finally confided to her teacher the reason for her state of mind: 'My mother's girlfriend doesn't like me,' " Francis said.
Francis' remarks, which he made Nov. 29, were reported Friday by La Civilta Cattolica, an Italian Jesuit magazine.
"The percentage of children studying in schools who have separated parents is very high," Francis said. "The situation in which we live now provides us with new challenges which sometimes are difficult to understand."
The pope received praise from gay-rights groups in July when he said, "If someone is gay and seeks the Lord with good will, who am I to judge?"
His latest remarks were interpreted by some Italian commentators as an opening to homosexual unions, in a week when Matteo Renzi, the new leader of Italy's center-left Democratic Party, has relaunched the idea of legislation allowing civil unions, including same-sex unions, in Italy.
Plans for civil unions in Italy have repeatedly been shot down by Catholic politicians.
On Sunday, the Vatican indicated that Francis' comments were more about reaching out to a changing society than giving it a stamp of approval.
"Speaking of an 'opening to gay couples' is paradoxical because the pope's speech was totally general and because even the small concrete example given by the Pope (a girl who is sad because her mother's girlfriend doesn't love her) alludes directly to the suffering of the children," Vatican spokesman Father Federico Lombardi told Vatican Radio.
On Dec. 29, a leading bishop said Francis was "shocked" by planned legislation in Malta that would allow gay couples to adopt children.
Bishop Charles Scicluna of Malta denounced same-sex adoption in his Christmas sermon, then told the Sunday Times of Malta that he had shared his concerns about the issue with Francis on Dec. 12. Francis, he said, had "encouraged" him to speak out.
Also Sunday, Pope Francis announced plans for a visit to the Holy Land in May. He said he would visit Amman, Jordan; Bethlehem and Jerusalem on May 24-26.