{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T19:38:54Z","timestamp":1740166734743,"version":"3.37.3"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T00:00:00Z","timestamp":1682380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 109-2311-B-033-001"],"award-info":[{"award-number":["MOST 109-2311-B-033-001"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,28]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Methylmercury (MeHg), a biotransformation product derived from mercury or inorganic mercury compounds in waterways, is a potent toxin that exerts hazardous effects on human health via environmental contamination. Previous studies have reported MeHg-induced impairment of nerve development in embryogenesis and placental development. However, the potential deleterious effects and regulatory mechanisms of action of MeHg on pre- and post-implantation embryo development are yet to be established. Experiments from the current study clearly demonstrate that MeHg exerts toxic effects on early embryonic development processes, including the zygote to blastocyst stage. Induction of apoptosis and decrease in embryo cell number were clearly detected in MeHg-treated blastocysts. Additionally, intracellular reactive oxygen species (ROS) generation and activation of caspase-3 and p21-activated protein kinase 2 (PAK2) were observed in MeHg-treated blastocysts. Importantly, prevention of ROS generation by pre-treatment with Trolox, a potent antioxidant, significantly attenuated MeHg-triggered caspase-3 and PAK2 activation as well as apoptosis. Notably, the downregulation of PAK2 via transfection of specifically targeted siRNA (siPAK2) led to marked attenuation of PAK2 activity and apoptosis and the deleterious effects of MeHg on embryonic development in blastocysts. Our findings strongly suggest that ROS serve as an important upstream regulator to trigger the activation of caspase-3, which further cleaves and activates PAK2 in MeHg-treated blastocysts. Activated PAK2 promotes apoptotic processes that, in turn, cause sequent impairment of embryonic and fetal development.<\/jats:p>","DOI":"10.1093\/toxres\/tfad030","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T16:33:39Z","timestamp":1682526819000},"page":"433-445","source":"Crossref","is-referenced-by-count":1,"title":["Role of activated p21-activated kinase 2 in methylmercury-induced embryotoxic effects on mouse blastocysts"],"prefix":"10.1093","volume":"12","author":[{"given":"Cheng-Kai","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Taoyuan General Hospital, Ministry of Health & Welfare , Taoyuan City 33004 , Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fu-Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Rehabilitation and Technical Aid Center, Taipei Veterans General Hospital , Taipei City 11217 , Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Hsun","family":"Huang","sequence":"additional","affiliation":[{"name":"Hungchi Gene IVF Center , Taoyuan District, Taoyuan City 330012 , Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Hsiung","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University , Chung Li District, Taoyuan City 32023 , Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,4,25]]},"reference":[{"issue":"5","key":"2023063007001518200_ref1","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1007\/s10534-016-9967-8","article-title":"Mini-review: toxicity of mercury as a consequence of enzyme 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