Study on the zona pellucida 4 (ZP4) gene sequence and its expression in the ovaries of patients with polycystic ovary syndrome.
BACKGROUND
Polycystic ovary syndrome (PCOS) is a common endocrine disorder of unknown pathology, involving reproductive and metabolic abnormalities. Oocyte-specific genes are a group of genes expressed exclusively in ovarian tissue; therefore, they can play an important role in ovarian pathologies such as PCOS. The zona pellucida 4 (ZP4) gene encodes glycoprotein which is a part of the extracellular matrix of oocyte.


METHODS
We analyzed 87 patients with PCOS, which were divided into four groups depending on their phenotype. In each patient, we performed profound clinical and biochemical analysis, including the measurement of serum androgens. The ovarian tissue samples were used to perform a real-time polymerase chain reaction and immunohistochemical staining using anti-ZP4 monoclonal antibodies. The ZP4 gene was sequenced from peripheral lymphocytes.


RESULTS
The expression of ZP4 was present in early antral follicles and was stronger in mature follicles. The subgroup of patients with eumenorrhea and without hyperandrogenism presented the highest expression of ZP4 in ovarian tissue. In one case, we found a mutation of the ZP4 gene. No correlations were found between the ZP4 expression level and biochemical or clinical indices.


CONCLUSIONS
Data from this and animal studies suggest a possible relationship between androgens and ZP4 expression. ZP4 expression is highest among patients with PCOS and a regular cycle, and this is a consequence of the presence of mature follicles in this group. In some patients with PCOS and infertility, ZP4 mutation can be found.
Department of Gynecological Endocrinology, Poznan University of Medical Sciences, Polna 33, 60-535, Poznan, Poland. blazejmeczekalski@yahoo.com.
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Meczekalski
Department of Molecular Virology, Faculty of Biology, Adam Mickiewicz University in Poznan, Umultowska 89, 61-614, Poznan, Poland.
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Nawrot
Department of Molecular Biology Techniques, Faculty of Biology, Adam Mickiewicz University in Poznan, Umultowska 89, 61-614, Poznan, Poland.
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Nowak
Department of Gynecological Endocrinology, Poznan University of Medical Sciences, Polna 33, 60-535, Poznan, Poland.
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Czyzyk
Pathomorphology Unit, Gynecological-Obstetrical Hospital in Poznan, Polna33, 60-535, Poznan, Poland.
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Kedzia
Department of Molecular Virology, Faculty of Biology, Adam Mickiewicz University in Poznan, Umultowska 89, 61-614, Poznan, Poland.
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Gozdzicka-Jozefiak
D000328:Adult; D000728:Androgens / Q000097:blood*; D001483:Base Sequence; D004527:Egg Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008597:Menstrual Cycle / Q000378:metabolism*; D009154:Mutation; D006080:Ovarian Follicle / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000378:metabolism*; D055815:Young Adult; D000072216:Zona Pellucida Glycoproteins
D000728:Androgens; D004527:Egg Proteins; D008562:Membrane Glycoproteins; C082833:ZP4 protein, human; D000072216:Zona Pellucida Glycoproteins
Oocyte-specific genes; Polycystic ovary syndrome; ZP4; Zona pellucida