Document Detail

Human oocyte maturation is dependent on LH-stimulated accumulation of the epidermal growth factor-like growth factor, amphiregulin.
MedLine Citation:
PMID:  20719813     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The LH surge promotes ovulation via activation of multiple signaling networks in the ovarian follicle. Studies in animal models have shown the importance of LH-induced activation of the epidermal growth factor (EGF)signaling network in critical peri-ovulatory events. We investigated the biological significance of regulatory mechanisms mediated by EGF-like growth factors during LH stimulation in humans.
METHODS: We characterized the EGF signaling network in mature human ovarian follicles using in vivo and in vitro approaches. Amphiregulin (AREG) levels were measured in 119 follicular fluid (FF) samples from IVF/ICSI patients. Biological activity of human FF was assessed using in vitro oocyte maturation, cumulus expansion and cell mitogenic assays.
RESULTS: AREG is the most abundant EGF-like growth factor accumulating in the FF of mature follicles of hCG-stimulated patients. No AREG was detected before the LH surge or before hCG stimulation of granulosa cells in vitro, demonstrating that the accumulation of AREG requires gonadotrophin stimulation. Epiregulin and betacellulin mRNA were detected in both human mural and cumulus granulosa cells, although at significantly lower levels than AREG. FF from stimulated follicles causes cumulus expansion and oocyte maturation in a reconstitution assay. Immunodepletion of AREG abolishes the ability of FF to stimulate expansion (P < 0.0001) and oocyte maturation (P < 0.05), confirming the biological activity of AREG. Conversely, mitogenic activity of FF remained after depletion of AREG, indicating that other mitogens accumulate in FF. FF from follicles yielding an immature germinal vesicle oocyte or from an oocyte that develops into an aberrant embryo contains lower AREG levels than that from follicles yielding a healthy oocyte (P = 0.008).
CONCLUSIONS: EGF-like growth factors play a role in critical peri-ovulatory events in humans, and AREG accumulation is a useful marker of gonadotrophin stimulation and oocyte competence.
A M Zamah; M Hsieh; J Chen; J L Vigne; M P Rosen; M I Cedars; M Conti
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-08-18
Journal Detail:
Title:  Human reproduction (Oxford, England)     Volume:  25     ISSN:  1460-2350     ISO Abbreviation:  Hum. Reprod.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-16     Completed Date:  2011-01-10     Revised Date:  2012-04-27    
Medline Journal Info:
Nlm Unique ID:  8701199     Medline TA:  Hum Reprod     Country:  England    
Other Details:
Languages:  eng     Pagination:  2569-78     Citation Subset:  IM    
Department of Obstetrics and Gynecology and Reproductive Sciences, Division of Reproductive Endocrinology and Infertility, University of California San Francisco, 2356 Sutter Street, 7th Floor, San Francisco, CA 94115, USA.
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MeSH Terms
Biological Markers / analysis,  metabolism
Chorionic Gonadotropin / metabolism
Epidermal Growth Factor / analysis,  metabolism
Follicular Fluid / chemistry,  metabolism
Glycoproteins / analysis,  metabolism*
Granulosa Cells / chemistry,  metabolism
Intercellular Signaling Peptides and Proteins / analysis,  metabolism*
Luteinizing Hormone / pharmacology*
Middle Aged
Mitosis / drug effects
Oocytes / chemistry,  growth & development*,  metabolism*
Oogenesis / drug effects*
Grant Support
Reg. No./Substance:
0/Biological Markers; 0/Chorionic Gonadotropin; 0/Glycoproteins; 0/Intercellular Signaling Peptides and Proteins; 0/betacellulin; 0/epiregulin; 117147-70-3/amphiregulin; 62229-50-9/Epidermal Growth Factor; 9002-67-9/Luteinizing Hormone

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