Understanding the Big Bang of life.

Astronomers believe they can accurately describe the initial moments after the Big Bang, the cosmic explosion that gave rise to the universe. Paul Primakoff envisions doing the same for the beginning of a new life. "Sperm and egg fusion is the Big Bang of development. We want to understand the seconds before and after," says the biologist from the University of California Davis School of Medicine.

As part of that endeavor, Primakoff and his colleagues have recently created a strain of mice unable to make fertilin-beta, a protein normally present on the surface of sperm. The males of this genetically engineered strain are infertile. While that was expected, the full explanation for this infertility has proven to be full of surprises.

Primakoff thought he knew the importance of fertilin-beta. After a sperm penetrates the zona pellucida, the protective barrier around the egg, it travels to the egg's outer membrane. The tip of the sperm's head then binds to the egg. Following this initial contact, the sperm prepares to fuse with the egg by turning on its side and making even greater contact with the egg. Primakoff knew from previous work that the sperm's fertilin-beta mediates this so-called lateral binding.

His assumption proved right. When mice are unable to make the protein, their sperm bind poorly to eggs and therefore fuse with them at a much lower rate. Yet the animals' infertility may stem from unanticipated consequences of fertilin-beta's absence, reports Primakoff. The investigators find that sperm lacking the protein fail to penetrate an egg's zona pellucida efficiently. Even more important, sperm lacking fertilin-beta rarely even made it from the uterus to the oviducts where eggs reside. It's unclear, says Primakoff, whether fertilin-beta participates directly in zona pellucida binding and the journey to an oviduct or whether its absence leads to other changes in sperm that affect both phenomena.