ABSTRACT
The growth and maturation of the ovarian follicle requires the coordinate function
of somatic cells and the oocyte. Over the past three decades, numerous growth factors
involved in the bidirectional signals between the somatic and germ cells have been
identified. A possible function of epidermal growth factor (EGF) signaling at selected
stages of follicle maturation had been proposed early on and is supported by many
observations of in vitro effects of this growth factor on steroidogenesis, oocyte
maturation, and cumulus expansion. However, attempts to link EGF levels in the follicular
fluid with the state of follicle and oocyte maturation have been inconclusive. More
recently, data generated using mouse genetic models perturbing ovulation and fertility
indicate that EGF-like growth factors, rather than EGF itself, accumulate in the follicle
at the time of ovulation. EGF-like growth factor mRNA is regulated by the luteinizing
hormone surge, and corresponding proteins are detected in the follicle. The EGF-like
growth factors amphiregulin, epiregulin, and betacellulin are potent stimulators of
oocyte maturation and cumulus expansion, and perturbation of this EGF network in vivo
impairs ovulation. Similar findings in species other than the mouse confirm an important
physiological role for this network at the time of ovulation. Whether this network
also plays a critical role in humans and whether it can be used as a biological marker
of follicle development or for the improvement of fertility remains to be determined.
This review summarizes the most recent findings on the EGF network during ovulation
and the potential clinical applications of manipulating this intercellular communication
pathway in the control of fertility.
KEYWORDS
Epidermal growth factor (EGF) - EGF-like factors - oocyte - follicular fluid
REFERENCES
Molecular mechanisms in ovulation . In: Findlay JK Molecular Biology of the Female Reproductive System. San Diego, CA;
Academic Press 1994: 207-258
ContiM@obgyn.ucsf.edu
