What can we learn about fertilization from cystic fibrosis?
- Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655
It is a curious and intriguing situation that mammalian sperm are introduced into the female reproductive tract in an infertile state and must be educated there before they are able to fertilize oocytes. The recognition that mammalian sperm must first be switched into a competent state, or capacitated, was exploited in the development of in vitro fertilization methods and has proved essential for the dependent technologies of clinical assisted reproduction and infertility treatments. Yet many aspects of the mechanisms of capacitation remain unclear (for recent reviews, see refs. 1 and 2). In a recent issue of PNAS, Xu et al. (3) advanced our understanding of capacitation by showing that CFTR, the cystic fibrosis transmembrane regulator, plays an essential role in some aspects of this process.
During capacitation there is a complex alteration of the biochemical, biophysical, and cell biological properties of sperm. These include (but are not restricted to) alterations in membrane potential and membrane sterol content, a rise in pHi and changes in other intracellular ion activities, and the enhanced tyrosine phosphorylation of an array of sperm proteins. As a result of this reprogramming, sperm become competent to fertilize (1, 2).
Capacitation is now understood as a physiological transformation that renders sperm better able to reach the oocyte surface. In this regard, the task confronting the mammalian sperm may be summarized as follows (Fig. 1 A). Fertilization typically occurs in the ampulla of the oviduct. Sperm must reach the vicinity of the oocyte; penetrate between the several thousand cumulus oophorus cells; contact and penetrate the oocyte extracellular matrix, or zona pellucida; and finally adhere …
*To whom correspondence should be addressed. E-mail: harvey.florman{at}umassmed.edu
