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Regulated expression of heparin‐binding EGF‐like growth factor (HB‐EGF) in the human endometrium: A potential paracrine role during implantation
Author(s) -
Lessey Bruce A.,
Gui Yaoting,
Apparao K.B.C.,
Young Steven L.,
Mulholland Joy
Publication year - 2002
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.10129
Subject(s) - epidermal growth factor , biology , paracrine signalling , stromal cell , leukemia inhibitory factor , heparin binding egf like growth factor , endocrinology , endometrium , medicine , growth factor , microbiology and biotechnology , receptor , cancer research , cytokine , immunology , interleukin 6 , biochemistry
Abstract Heparin‐binding epidermal growth factor (HB‐EGF) is a recently identified member of the EGF growth factor family found to be expressed in the uterus of both mouse and human at the time of implantation. In the present study, we investigated the expression patterns of HB‐EGF in normal cycling endometrium and compared its expression with the fertility‐associated endometrial epithelial biomarkers α v β 3 integrin, leukemia inhibitory factor (LIF) and homeobox gene, HOXA‐10. RNase protection assay (RPA) using RNA made from endometrium collected from different phases of the menstrual cycle demonstrated increased HB‐EGF expression during the mid‐secretory phase, a pattern similar to, but slightly preceding the expression of α v β 3 integrin and HOXA‐10. In vitro studies demonstrated stimulation of HB‐EGF expression by estradiol‐17β (E 2 ) and progesterone (P 4 ) alone or in combination in stromal cells. Combined treatment with E 2 + P 4 was, however, required to stimulate epithelial HB‐EGF expression. In vitro experiments demonstrated the ability of HB‐EGF to stimulate epithelial expression of the key endometrial proteins including LIF, HOXA‐10, and the β 3 integrin subunit. Each has previously been demonstrated to be an important epithelial biomarker expressed during the implantation window. In addition, conditioned media from endometrial stromal cells treated with E 2 + P 4 + relaxin mimicked the stimulatory effect of HB‐EGF on epithelial expression of the β 3 integrin subunit. The stimulatory effect of the stromal‐conditioned medium was blocked by antibodies that neutralize a known receptor for HB‐EGF. These data suggest that uterine receptivity may be regulated in part by the stromal‐derived HB‐EGF. Mol. Reprod. Dev. 62:446–455, 2002. © 2002 Wiley‐Liss, Inc.