EGF-Like Growth Factors As Mediators of LH Action in the Ovulatory Follicle

Abstract

Before ovulation in mammals, a cascade of events resembling an inflammatory and/or tissue remodeling process is triggered by luteinizing hormone (LH) in the ovarian follicle. Many LH effects, however, are thought to be indirect because of the restricted expression of its receptor. Here, we demonstrate that LH stimulation induces the transient and sequential expression of the epidermal growth factor (EGF) family members amphiregulin, epiregulin, and beta-cellulin. Incubation of follicles with these growth factors recapitulates the morphological and biochemical events triggered by LH, including cumulus expansion and oocyte maturation. Thus, these EGF-related growth factors are paracrine mediators that propagate the LH signal throughout the follicle.

Regulation of sheep oocyte maturation using cAMP modulators

“…In-vivo, the surge of gonadotrophins prior to ovulation overrides natural meiotic inhibition and specific epidermal growth factor (EGF)-like peptides initiate cascades that induce oocyte maturation [31]. In comparison, mechanical removal of the oocyte from the follicular environment results in spontaneous resumption of meiosis [17].…”

Gene expression profiling of granulosa cells from PCOS patients following varying doses of human chorionic gonadotropin

“…Epidermal growth factor (EGF)-like growth factors have been previously reported to be involved in cumulus expansion and oocyte maturation [32]. Among those, amphiregulin and epiregulin have been found to be rapidly upregulated in response to LH in periovulatory mouse granulosa cells [8] and increased the in vitro maturation rates of human and rhesus oocytes [5,33,44].…”

A novel compound heterozygous mutation of the luteinizing hormone receptor –implications for fertility

“…All oocytes retrieved came from small follicles less than 6 mm in diameter in which the bevel of the retrieval needle was inserted and twirled to literally curette the COC from the follicle wall. In terms of oocyte maturation in vitro, several different concentrations of EGF-like factors have been studied but both the timing and optimal concentration for oocyte maturation remains to be determined [12][13][14]. In the present case report, amphiregulin was added to the medium with the aim of mimicking activation of EGF-like activity normally induced by ligand binding to the LHCGR.…”

“…A total of 7 oocytes was retrieved one of which was mature (MII) and 6 were germinal vesicle (GV) stage. In vitro maturation was performed with the EGF analogue amphiregulin added to the culture media in a concentration of 100 ng/ml [12][13][14] and another two oocytes reached the MII stage. ICSI was performed, 3 embryos developed and were successfully cultured up to day 5 but arrested before reaching the blastocyst stage and embryo transfer was not performed.…”