PARIS – Serena Williams laughed at her own jokes and sounded an upbeat tone — or one as positive, at least, as could be expected from a player whose latest bid for a record-tying 24th Grand Slam title ended because of injury, as did her season, probably.

Williams tried to warm up for her second-round match at Roland Garros on Wednesday but huddled afterward with her coach and determined that if walking on the Achilles' tendon she hurt at the U.S. Open nearly three weeks ago was difficult, then trying to run and compete made little sense.

"If it was my knee, that would be more really devastating for me. But this is something that just happened, and it's super acute. That's totally different. I feel like my body is actually doing really, really well," said Williams, who turned 39 on Saturday. "I just ran into, for lack of a better word, bad timing and bad luck, really, in New York."

Williams withdrew about an hour before she would have played Tsvetana Pironkova at Court Philippe Chatrier, her earliest exit from a major tournament in six years and the most significant development in Paris on Day 4, which also included a straight-set loss by U.S. Open runner-up Victoria Azarenka and straightforward wins for Rafael Nadal and Dominic Thiem over a couple of American men.

Williams' departure, and the 10th-seeded Azarenka's 6-2, 6-2 dismissal by 161st-ranked Anna Karolina Schmiedlova — someone who lost 13 consecutive Grand Slam matches until defeating Williams' older sister, Venus, earlier this week — meant none of the four female semifinalists at Flushing Meadows made it past the second round at Roland Garros.

Champion Naomi Osaka didn't make the trip to France at all; No. 21 seed Jennifer Brady was upset in her opening match by a 17-year-old qualifier.

In other matches:

• American teenager Coco Gauff's French Open debut ended in the second round after she double-faulted 19 times in a 4-6, 6-2, 7-5 loss to 159th-ranked qualifier Martina Trevisan.

For Trevisan, a 26-year-old from Italy, this was her first victory in a Grand Slam match played to its conclusion.

• Locked up by what she called a "total body cramp," Kiki Bertens had to use a wheelchair to leave Court 14 after saving a match point and collapsing to her back at the end of a 7-6 (5), 3-6, 9-7 victory over Italy's Sara Errani.

Errani, who swore in Italian as she walked off the court, accused her fifth-seeded Dutch opponent of faking the pain.

Bertens said she was in the treatment room for 45 minutes after the match and didn't stop cramping for half an hour.

• Nadal reached the third round by beating American Mackenzie McDonald 6-1, 6-0, 6-3.

The No. 2-seeded Spaniard is looking to win his record-extending 13th French Open title and equal Roger Federer's men's record of 20 major titles overall.

Nadal improved his record at Roland Garros to 95-2.