Any better understanding of the cascade of events, where mistakes in IVF often occur, would be useful, Visconti says. Conducting experiments with mouse sperm in vitro, he and colleagues at UMass Amherst, with others at Weill Cornell Medical College, University of Hawaii Medical School, Asahikawa Medical University Japan, Universidad Nacional de Rosario and Facultad de Medicina Argentina and Universidad Nacional Autnoma de Mxico made two discoveries that should help.
In the PNAS study, the researchers experimented with increasing intracellular calcium using the calcium ionophore, A23187. Calcium is known to play a role late in the sperm capacitation process, after many earlier steps in pathways that depend on soluble adenylyl cyclase, cyclic adenosine monophosphate (cAMP), protein kinase A (PKA) and other enzyme cascades have taken place.
A major drawback of adding calcium ionophore, however, is that it overwhelms the sperm with too much and quickly immobilizes them, Visconti notes. But he and colleagues found that they could get around this by simply washing the excess away. Thus they basically bypass early capacitation stages by applying the calcium ionophore, wash it away, and the sperm proceed with capacitation.
Under these conditions, the authors report, ionophore-treated sperm fertilized 80 percent of eggs, which developed into normal offspring. Their data indicate that ionophore-treated mouse sperm can fertilize ova even when the cAMP/PKA signaling pathway is inhibited.
Visconti credits his co-authors Hiroyuki Tateno in Japan and Ryuzo Yanagimachi in Hawaii with the idea of washing ionophore away after use. He points out, "Until they conceived it, no one had thought of this trick. They did the first experiments," Visconti explains. "Later, our experiments demonstrated that by treating the sperm with calcium ionophore, we were activating these cells far downstream of the normal biologi
|Contact: Janet Lathrop|
University of Massachusetts at Amherst