ArticleHuman reproduction (Oxford, England)2010
Human oocyte maturation is dependent on LH-stimulated accumulation of the epidermal growth factor-like growth factor, amphiregulin.
Article in Human reproduction (Oxford, England), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 121 citations in OpenAlex.
- Nomogram models to predict low fertilisation rate and total fertilisation failure in patients undergoing conventional IVF cycles.BMJ open · 2022Trial
- Review
- Empty Follicle Syndrome: Current Therapeutic Approaches and the Role of Triggering Agents in Assisted Reproductive Technology.Medical sciences (Basel, Switzerland) · 2026Review
- Article
- Improvement of fertility in female mice by treatment with novel telomerase-increasing compounds.Reproductive biology and endocrinology : RB&E · 2026Article
- Advances, Mechanisms, and Clinical Perspectives for the In Vitro Maturation of Human Oocytes.International journal of molecular sciences · 2025Review
- Role of Granulosa Cell Dysfunction in Women Infertility Associated with Polycystic Ovary Syndrome and Obesity.Biomolecules · 2025Review
- Impact of Amphiregulin on Oocyte Maturation and Embryo Quality: Insights from Clinical and Molecular Perspectives.Geburtshilfe und Frauenheilkunde · 2025Article
- New insights into the ovulatory process in the human ovary.Human reproduction update · 2025Review
- Role of epiregulin levels in polycystic ovary syndrome patients: new findings and clinical significance.Revista da Associacao Medica Brasileira (1992) · 2025Article
- Article
- Activation of P2X7 Receptor Mediates the Abnormal Ovulation Induced by Chronic Restraint Stress and Chronic Cold Stress.Biology · 2024Article
- LH level on trigger day, number of follicles ≥16 mm but <18 mm, and number of retrieved oocytes are independent risk factors for polyspermy in gonadotropin-releasing hormone antagonist protocol.Frontiers in endocrinology · 2024Article
- The role of amphiregulin in ovarian function and disease.Cellular and molecular life sciences : CMLS · 2023Review
- Interaction between epidermal growth factor receptor and C-C motif chemokine receptor 2 in the ovulatory cascade.Frontiers in cell and developmental biology · 2023Article
- Perfluorooctanoic acid (PFOA) promotes follicular growth and alters expression of genes that regulate the cell cycle and the Hippo pathway in cultured neonatal mouse ovaries.Toxicology and applied pharmacology · 2022Article
- Article
- A Case-Control Study of Follicular Fluid Cytokine Profiles in Women with Diminished Ovarian Reserve.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
- Compromised Cumulus-Oocyte Complex Matrix Organization and Expansion in Women with PCOS.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
- Characterization of the roles of amphiregulin and transforming growth factor β1 in microvasculature-like formation in human granulosa-lutein cells.Frontiers in cell and developmental biology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe 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.
methodsWe 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.
resultsAREG 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).
conclusionsEGF-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.
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