In humans, a few hundred million spermatozoa enter the female reproductive tract but only one out of million spermatozoa arrive at the fertilization site in the oviduct. It is unknown whether or how the hundreds of sperm that reach the oviduct are molecularly different from those that lag behind and never reach the fertilization site. During the journey, mammalian spermatozoa gradually obtain the fertilizing ability through extensive biochemical and functional changes – a process called “capacitation.” Reconstitution of capacitation in a test tube enabled in vitro fertilization (IVF), through which nearly 5 million babies have been born. However, the way that spermatozoa interact with the egg is substantially different between in vitro and in vivo. As most previous studies are based on population averages of millions of in vitro capacitated spermatozoa, it is unclear which changes are physiologically relevant to sperm motility and fertilizing capability. 

We are studying during in vivo capacitation, whether individual sperm display unique molecular signatures that dictate the fertilizing capacity. To directly assess a small number of in vivo capacitated sperm in the oviduct that actually reach the egg, we develop in situ molecular imaging of single sperm cells in the intact tissue.

Male factor diagnosis comprises more than 30% of infertility among assisted reproductive technology (ART) users. When we figure out molecular signatures of sperm that reach and fertilize the egg in vivo and in situ, we may dramatically improve ART by enriching sperm with the fertile molecular signatures.