The closest thing I can use as a reference is soccer. I was a decent soccer player when younger. Not professional or anything, but I did ok. I played against men on the U.S. national team and from other national teams. After playing against a kid on the German under 21 national team, I knew soccer wasn't in my professional future. I couldn't keep up with the guy and his skill-set was ridiculous. The gap between me and U.S. national youth players was much smaller and I didn't consider myself terribly over-matched, but when I went up against them, it was 90 minutes of intensity and letting down for a second would result in having my ass handed to me.
However, when I watched women play, I could demonstrably tell the difference. The speed, strength and skill was noticeably different. The U.S. women's national soccer team would most likely get beat against most Division 1 men's soccer teams (maybe most division II teams as well). Badly. My amateur club teams back when I was 17-18 could have competed against women's pro teams. Probably would have lost some and won some. In sports, you simply cannot substitute for speed and strength. I'd imagine that this is just as true in tennis as any other sport. Serena is an outstanding tennis player and among the best females to have ever played, but she would not be competitive in the men's circuit.
In fact, there was a women who played in the boys soccer league for several seasons. She was really good. However, she had to stop at a certain point because she was getting the hell beat out of her. She held up fine against 13 and 14 year old boys. Once those boys started developing and were 16-17, she had to switch leagues.