(left) Mouse sperm cells stained with an antibody that recognizes fatty acid binding protein 9 (FABP9), a protein that was differentially phosphorylated in the capacitation study. (right) Structure of FABP9.

To locate the specific site of phosphorylation, Platt and his colleagues first induced capacitation in sperm. Proteins from the capacitated sperm and proteins from a non-capacitated population were then extracted and digested into smaller segments called peptides. Using tandem mass spectrometry (MS/MS), an analytical technique utilized in his laboratory, Platt was able to determine the amino acid sequence of each peptide and to determine where each was phosphorylated. By comparing the phosphorylation status of the samples, Platt and his colleagues were able to identify 55 specific sites whose level of modification changed as a result of the capacitation process.

Contraceptives and Improved Fertility

His research may offer insight required to develop an entirely new contraceptive, even a male version of the birth control pill.

“These applications are currently hypothetical at this point, but the implications for contraceptives resulting from this research are promising,” Platt said. He noted that there could be several different options that could be developed using this and future research, including a drug for males that specifically targets the individual sites of protein phosphorylation in the developing sperm or a novel spermicide that prevents capacitation from occurring in sperm residing in the female reproductive tract.

In addition, the research provides important insight into male infertility. “Certain types of male infertility could be caused by a mutation of a single amino acid on a critical protein that prevents the sperm from ever undergoing the capacitation process,” Platt said. “If you could correct that specific mutation or design a drug which mimics phosphorylation on that particular amino acid, for example, you might be able to improve fertility.”

Researchers and Funding 

Platt was joined in the research by Ana Maria Salicioni and Pablo Visconti of the University of Massachusetts at Amherst and Donald F. Hunt of the University of Virginia. The research was funded in part by the National Institutes of Health.