NEW YORK (AP) — Serena Williams took a medical timeout because of a problem with her right foot and later double-faulted on the last two points as she and sister Venus lost in the doubles quarterfinals at the U.S. Open.

Serena, left, and Venus Williams slap hands between points against Garbine Muguruza and Carla Suarez Navarro, of Spain, during a doubles match at the 2014 U.S. Open tennis tournament, Sunday, Aug. 31, 2014, in New York. (AP Photo/Seth Wenig)

The Williams sisters, owners of 13 Grand Slam doubles titles, were beaten 7-6 (5), 6-4 Tuesday by the fourth-seeded Russian duo of Ekaterina Makarova and Elena Vesnina.

Serena’s serve was broken early in each of the first two sets, and then again in the final game.

She and Venus are 4-3 in doubles in 2014, with two of the losses against Makarova and Vesnina. They also played each other at Dubai in February.

In singles, the top-seeded Serena and 17th-seeded Makarova could face each other again in the semifinals. They play their quarterfinal matches in that event Wednesday, and it was not clear how much Serena’s foot would be an issue against her opponent, 11th-seeded Flavia Pennetta.

During the changeover after the third game of the second set of doubles, Williams removed her right shoe and sock so a trainer could treat that foot during a medical timeout.

Venus Williams, right, misses a shot from Elena Vesnina, center, as Serena Williams, left, looks on during a quarterfinals doubles match against Vesnina and Ekaterina Makarova, of Russia, during the 2014 U.S. Open tennis tournament, Tuesday, Sept. 2, 2014, in New York. (AP Photo/John Minchillo)

The Williams sisters have not been to a major semifinal in doubles since losing in that round at last year’s U.S. Open. Their last Grand Slam doubles trophy came at Wimbledon in 2012.

When they played together at Wimbledon this year, they stopped after three games in the second round on July 1, after Serena served four consecutive double-faults. She had looked disoriented during warmups, having trouble grabbing tennis balls tossed to her by ballkids. The reason given that day was that she was ill.