* World number one Serena upset by Spain's Muguruza
* Sister Venus falls to Slovak teenager Schmiedlova
* Djokovic eases past Frenchman Chardy in three sets
* Fourth seed Federer breezes into third round
PARIS, May 28 (Reuters) - Serena Williams was caught cold at the French Open on Wednesday by a Spanish 20-year-old who trounced the defending champion 6-2 6-2 in the second round to provide the shock of the tournament.
The American's defeat by Garbine Muguruza came an hour after her elder sister Venus was shown the exit by another youngster, 19-year-old Anna Schmiedlova of Slovakia, a defeat which ruined the chance of possibly the last meeting of the famed siblings at a grand slam.
But Maria Sharapova, last year's losing finalist, and Agnieszka Radwanska, the highest surviving women's seed at three, struggled through on a day when long sleeves and leggings were needed to ward off the Paris chill.
The top men, Novak Djokovic, Roger Federer, Tomas Berdych and Milos Raonic, showed few frailties in progressing to the third round with the loss of one set between them.
Right from the start of her match on court Suzanne Lenglen, Serena never looked the force who has won 17 major titles. Her serve was broken twice early in the first set and she looked leaden-footed as she was kept on the move by Muguruza.
The Spaniard, ranked 35 in the world, did not release the pressure for the full 64 minutes and the match became a repeat of the nightmare of 2012, when Williams lost in the first round, not the glory of 2013 when she beat Sharapova in the final.
"I don't think anything worked for me. It was just one of those days, you can't be on (your game) every day," said Serena. "It's not the end of the world, there's always next year."
The world number one said she was proud of Muguruza, who leapt about the court in ecstasy after the final point.
"It's amazing," Muguruza said. "I had to be really aggressive and focused.
"Today is a great day, I'm so happy," the Spaniard shouted.
Later Muguruza told a news conference: "She (Serena) said that if I continue playing like this, I can win the tournament. I said: 'I will try, I will try'."
After the defeat of China's Li Na in the first round on Tuesday, it is the first time since tennis turned professional in 1968 that the top two women's seeds have failed to reach the third round at a grand slam.
It is also the third time, after 2004 and 2008, that both Williams sisters have lost on the same day at the French Open. They had been due to meet in the third round here.
Venus, the 29th seed, has never won the claycourt grand slam in 16 visits and, now 33, she may have to accept she never will after a 2-6 6-3 6-4 loss.
"This is the biggest win of my life," said Schmiedlova, ranked 56 in the world, who broke down when expressing how much Venus had meant to her when she was growing up.
Seventh seed Sharapova, in Serena's quarter of the draw, also had an off day against Tsvetana Pironkova but eventually prevailed 7-5 6-2 against the Bulgarian.
"I think it's always a challenge to go into a match knowing that it's going to be cold and might be a bit windy. So you have to mentally be prepared for that," Sharapova said. "I started off quite cold, wasn't moving my feet enough."
Radwanska beat Karolina Pliskova of Czech Republic 6-3 6-4 and one ray of American sunshine among the clouds was Taylor Townsend, an 18-year-old playing in her first grand slam, who hung in there to beat Alize Cornet of France 6-4 4-6 6-4.
Serbia's Djokovic, the second seed, despatched Jeremy Chardy of France 6-1 6-4 6-2 while Federer, seeded fourth, won 6-3 6-4 6-4 against Diego Sebastian Schwartzman of Argentina, a player the Swiss had never seen before.
Chardy, who beat Federer at the Rome Masters earlier this month, spelled out why Djokovic is fancied to end eight-times champion Rafa Nadal's reign here.
"He was simply stronger than me, bigger than me in all compartments. You're always under pressure. He knows everything. He can do everything," he said.
Czech Berdych, the sixth seed, started slowly before beating Aleksandr Nedovyesov of Kazakhstan 6-7(4) 6-4 7-5 6-3. Eighth seed Raonic of Canada got past Jiri Vesely of the Czech Republic 7-6(4) 6-4 6-1.
As night and the rain fell on Roland Garros, American 10th seed John Isner felled Kazakh Mikhail Kukushkin 6-7(6) 7-6(4) 6-3 7-6(4).
Sharapova looked frustrated with her own performance on a windy Philippe Chatrier court and she needed a heavy net cord in her favour on set point to take the first set.
Pironkova, who had a lengthy massage between the sets, stayed with the Russian until she was broken in the sixth game of the second, and Sharapova ended it in style by breaking her opponent in the final game.
Flavia Pennetta of Italy, seeded 12th, joined the Williams sisters in heading for the exit after going down 5-7 6-4 6-2 to Sweden's Johanna Larsson. (Editing by Mark Meadows)