{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T13:55:01Z","timestamp":1770818101853,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ac\u0131badem Mehmet Ali Aydinlar University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Diminished ovarian reserve is characterized by a decrease in oocyte count and estrogen levels, which leads to infertility. The genetic and epigenetic mechanisms in MI to MII transition or complete MII phase in the oocyte maturation process estrogen receptor alpha and piRNA relationship were evaluated. Methods: This study analyzed 100 cumulus oophorous complex samples from normoresponder and DOR patients undergoing IVF, subdivided into metaphase I and metaphase II stages. To elucidate the ER-\u03b1, PIWIL3, piR-651, and piR-823 genes qRT-PCR was used and qualitative ER-\u03b1 protein expressions were determined by immunohistochemistry. Pearson\u2019s correlation analysis was utilized to evaluate the interactions between genes within each experimental group. Results: The DOR samples exhibited significant downregulation of ER-\u03b1 gene and protein expression compared to the NOR controls. PIWIL3 gene, piR-651, and piR-823 expressions reduced in DOR MI and MII. Strong positive correlations among ER-\u03b1, PIWIL3, piR-651, and piR-823 were observed in NOR, whereas DOR showed weaker correlations and immunohistochemistry verified lower ER-\u03b1 protein levels in DOR. Conclusions: The disruption of ER-\u03b1 and piRNA-related gene networks in DOR may underlie the suboptimal maturation of oocytes, and monitoring ER-\u03b1, PIWIL3, piR-651, and piR-823 expressions could facilitate early determination of maturation stages and improve assessment of ovarian reserve. The potential for transposition to MII in NOR and DOR oocytes was observed in relation to the association between ER-\u03b1 protein\/gene expression and PIWIL3, which regulates ER-\u03b1. Moreover, piR-651 and piR-823, whose expressions depend on estrogen level, indirectly regulate oocyte maturation from MI to MII in both NOR and DOR epigenetically. We suggest that the MI and MII stages of oocytes could be determined earlier in NOR and DOR cases by controlling ER-\u03b1, PIWIL3, piR-651 and piR-823 expressions. These molecular markers indicate promise for diagnostic applications in reproductive medicine, warranting further validation in larger cohorts.<\/jats:p>","DOI":"10.3390\/genes17020223","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T11:13:15Z","timestamp":1770808395000},"page":"223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Association Between Estrogen Receptor-\u03b1 and PIWIL3\/piR-651\/piR-823 Complex Regulates MI to MII Transposition in Normoresponder and Diminished Ovarian Reserve Cases"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3771-3277","authenticated-orcid":false,"given":"\u00c7a\u011fr\u0131","family":"\u00d6ner","sequence":"first","affiliation":[{"name":"Department of Medical Biology, Medical Faculty, K\u0131rklareli University, 39100 K\u0131rklareli, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8682-5604","authenticated-orcid":false,"given":"Damla","family":"Kolcuo\u011flu","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Medical Faculty, K\u0131rklareli University, 39100 K\u0131rklareli, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2739-7760","authenticated-orcid":false,"given":"Senem","family":"Aslan \u00d6zt\u00fcrk","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Medical Faculty, Maltepe University, 34844 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5710-257X","authenticated-orcid":false,"given":"Nergis \u00d6zlem","family":"K\u0131l\u0131\u00e7","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Medical Faculty, Maltepe University, 34844 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1441-4533","authenticated-orcid":false,"given":"Duygu","family":"K\u00fct\u00fck","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Medical Faculty, Maltepe University, 34844 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4478-7514","authenticated-orcid":false,"given":"Belgin","family":"Selam","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, Acibadem Mehmet Ali Aydinlar University, 34752 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u0130brahim Or\u00e7un","family":"Olcay","sequence":"additional","affiliation":[{"name":"In Vitro Fertilization Laboratory, Bah\u00e7eci Umut Assisted Reproduction Center, 34662 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3251-1043","authenticated-orcid":false,"given":"Ertu\u011frul","family":"\u00c7olak","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Medical Faculty, Eskisehir Osmangazi University, 26040 Eskisehir, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1007\/s11154-023-09819-z","article-title":"Follicular fluid composition and reproductive outcomes of women with polycystic ovary syndrome undergoing in vitro fertilization: A systematic review","volume":"24","author":"Moreira","year":"2023","journal-title":"Rev. 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