{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:25:14Z","timestamp":1790357114258,"version":"4.1.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Previous studies have shown that berberine, an isoquinoline alkaloid isolated from several traditional Chinese herbal medicines, suppresses growth and induces apoptosis in some tumor cell lines. It has also been shown that berberine possesses anti-atherosclerosis and antioxidant activities in hyperlipidemic model rats. Our previous study in mice found that berberine causes harmful effects on preimplantation and postimplantation embryonic development, both in vitro and in vivo, by triggering reactive oxygen species (ROS)-mediated apoptotic cascades in mouse blastocysts. In the current investigation, we further showed that berberine treatment has distinct dose-dependent effects on oocyte maturation and subsequent development. Preincubation of oocytes with 2.5\u00a0\u03bcM berberine significantly enhanced maturation and in vitro fertilization (IVF) rates, with subsequent beneficial effects on embryonic development. In contrast, preincubation with 10\u00a0\u03bcM berberine negatively impacted mouse oocyte maturation, decreased IVF rates and impaired subsequent embryonic development. Similar dose-dependent effects were also demonstrated in vivo. Specifically, intravenous injection of berberine significantly enhanced mouse oocyte maturation, IVF rate and early-stage embryo development after fertilization at a dose of 1\u00a0mg\/kg body weight but significantly impaired oocyte maturation and IVF rates and caused harmful effects on early embryonic development at a dose of 5\u00a0mg\/kg. Mechanistically, we found that berberine enhanced intracellular ROS production and apoptosis of oocytes at a concentration of 10\u00a0\u03bcM but actually significantly decreased total intracellular ROS content and had no apoptotic effect at a concentration of 2.5\u00a0\u03bcM. Moreover, pretreatment of oocytes with Ac-DEVD-cho, a caspase-3\u2013specific inhibitor, effectively blocked berberine-induced negative impacts on oocyte maturation, fertilization and subsequent development. Collectively, these findings establish the dose-dependent beneficial versus deleterious effects of berberine and suggest that the mechanism underlying the deleterious effects of berberine involves a caspase-3\u2013dependent apoptotic process acting downstream of an increase in intracellular ROS levels.<\/jats:p>","DOI":"10.1093\/toxres\/tfaa043","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T11:18:31Z","timestamp":1591096711000},"page":"431-443","source":"Crossref","is-referenced-by-count":11,"title":["Dose-dependent beneficial and harmful effects of berberine on mouse oocyte maturation and fertilization and fetal development"],"prefix":"10.1093","volume":"9","author":[{"given":"Chien-Hsun","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Taoyuan General Hospital, Ministry of Health & Welfare, hongshan Road, Taoyuan District, Taoyuan City 33004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu-Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Rehabilitation and Technical Aid Center, Taipei Veterans General Hospital, Shipai Road, Beitou District, Taipei City 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Hsiung","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Bioscience Technology, Center for Nanotechnology, Chung Yuan Christian University, Chung Li District, Taoyuan City 32023, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,7,1]]},"reference":[{"key":"2020090213224437300_ref1","first-page":"341","article-title":"In vitro effect of berberine induced apoptosis in PC3 cells","volume":"32","author":"He","year":"2012","journal-title":"Chin J 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