The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Erbb4 regulates the oocyte microenvironment during folliculogenesis
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders leading to infertility in women affecting reproductive, endocrine and metabolic systems. Recent genomewide association studies on PCOS cohorts revealed a single nucleotide polymorphism (SNP) in the ERBB4 receptor tyrosine kinase 4 gene, but its role in ovary development or during folliculogenesis remains poorly understood. Since no genetic animal models mimicking all PCOS reproductive features are available, we conditionally deleted Erbb4 in murine granulosa cells (GCs) under the control of Amh promoter. While we have demonstrated that Erbb4 deletion displayed aberrant ovarian function by affecting the reproductive function (asynchronous oestrous cycle leading to few ovulations and subfertility) and metabolic function (obesity), their ovaries also present severe structural and functional abnormalities (impaired oocyte development). Hormone analysis revealed an up-regulation of serum luteinizing hormone, hyperandrogenism, increased production of ovarian and circulating anti-Müllerian hormone. Our data implicate that Erbb4 deletion in GCs leads to defective intercellular junctions between the GCs and oocytes, causing changes in the expression of genes regulating the local microenvironment of the follicles. In vitro culture assays reducing the level of Erbb4 via shRNAs confirm that Erbb4 is essential for regulating Amh level. In conclusion, our results indicate a functional role for Erbb4 in the ovary, especially during folliculogenesis and its reduced expression plays an important role in reproductive pathophysiology, such as PCOS development.
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“ERBB4 plays a role in normal follicle development and disturbances in ERBB4 levels may lead to ovarian dysfunction [40].”
From Hsa-mir-548 family expression in human reproductive tissues (2021) · cites this paper as [40]
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“In addition, the “Translocation of SLC2A4 (GLUT4) to the plasma membrane” targeted by hsa-mir-548ba in both CGC and MGC, as well as “Signalling by ERBB4” targeted by hsa-miR-548b-5p in MGC, demonstrate the importance of the corresponding miRNAs in ovarian functions [39, 40].”
From Hsa-mir-548 family expression in human reproductive tissues (2021) · cites this paper as [40]
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Polycystic ovary syndrome: etiology, pathogenesis and diagnosis
Goodarzi, M. O., Dumesic, D. A., Chazenbalk, G., & Azziz, R. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2010.217 · Cited by 1,488
Mouse Estrous Cycle Identification Tool and Images
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Gassmann, M., Casagranda, F., Orioli, D., Simon, H., Lai, C., Klein, R., & Lemke, G. (1995) · Nature · doi:10.1038/378390a0 · Cited by 1,148
γ-Secretase Cleavage and Nuclear Localization of ErbB-4 Receptor Tyrosine Kinase
Ni, C.-Y., Murphy, M. P., Golde, T. E., & Carpenter, G. F. (2001) · Science · doi:10.1126/science.1065412 · Cited by 875
Anti-Mullerian Hormone Inhibits Initiation of Primordial Follicle Growth in the Mouse Ovary
Durlinger, A. L. L., Gruijters, M. J. G., Kramer, P., Karels, B., Ingraham, H. A., Nachtigal, M. W., Uilenbroek, J. T. J., Grootegoed, J. A., & Themmen, A. P. N. (2002) · Endocrinology · doi:10.1210/en.143.3.1076 · Cited by 843
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Research works printed but not linked: 2
- Sato, 2018, Health and Medicine—Medical Genetics; Researchers at Tokushima University Target Medical Genetics (Genome-Wide Association Study Identifies ERBB4 on 2q34 as a Novel Locus Associated with Sperm Motility in Japanese Men)
- Marshall, 2012, All women with PCOS should be treated for insulin resistance, 18
Cited by
Deconstructing a Syndrome: Genomic Insights Into PCOS Causal Mechanisms and Classification
Dapas, M., & Dunaif, A. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnac001 · Cited by 300
Hsa-mir-548 family expression in human reproductive tissues
Rooda, I., Kaselt, B., Liivrand, M., Smolander, O.-P., Salumets, A., & Velthut-Meikas, A. (2021) · BMC Genomic Data · doi:10.1186/s12863-021-00997-w · Cited by 17
Metadata
- Authors
- Veikkolainen, V., Ali, N., Doroszko, M., Kiviniemi, A., Miinalainen, I., Ohlsson, C., Poutanen, M., Rahman, N., Elenius, K., Vainio, S. J., & Naillat, F.
- Affiliations
- Institute of Biomedicine and MediCity Research Laboratory, University of Turku, FI-20520 Turku, Finland
- Organogenesis Laboratory, Department of Medical Biochemistry and Molecular Biology, Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland
- Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, FI-20520 Turku, Finland
- Electron Microscopy Unit, Biocenter Oulu, University of Oulu, FI-90220 Oulu, Finland
- Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-41345 Gothenburg, Sweden
- Department of Immunology Genetics and Pathology, Section for Neuro-oncology, Uppsala University, 752 36 Uppsala, Sweden
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-07-27
- Volume
- 29
- Issue
- 17
- Pages
- 2813-2830
- ISSN
- 0964-6906
- 1460-2083
- Cited by
- 31
- References
- 60
- Language
- en
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Funders
- University of Oulu Profi (311934)
- Academy of Finland (206038, 121647, 250900, 260056, 251314)
- Tekes BioRealHealth (24302443)
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- Veikkolainen, V., Ali, N., Doroszko, M., Kiviniemi, A., Miinalainen, I., Ohlsson, C., Poutanen, M., Rahman, N., Elenius, K., Vainio, S. J., & Naillat, F. (2020). Erbb4 regulates the oocyte microenvironment during folliculogenesis. Human Molecular Genetics. https://doi.org/10.1093/hmg/ddaa161
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