期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 24, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/ijms241210003
关键词
oocyte; oxidative stress; DNA double-strand break; hexavalent chromium; RAD51; microtubule; polar body extrusion
Environmental and occupational exposure to hexavalent chromium, Cr(VI), leads to female reproductive failures and infertility. Cr(VI) is widely used and has detrimental effects on both male and female reproductive systems. The current study investigates the mechanism of Cr(VI) in causing meiotic disruption of MII oocytes, leading to oocyte incompetence in superovulated rats.
Environmental and occupational exposure to hexavalent chromium, Cr(VI), causes female reproductive failures and infertility. Cr(VI) is used in more than 50 industries and is a group A carcinogen, mutagenic and teratogenic, and a male and female reproductive toxicant. Our previous findings indicate that Cr(VI) causes follicular atresia, trophoblast cell apoptosis, and mitochondrial dysfunction in metaphase II (MII) oocytes. However, the integrated molecular mechanism of Cr(VI)-induced oocyte defects is not understood. The current study investigates the mechanism of Cr(VI) in causing meiotic disruption of MII oocytes, leading to oocyte incompetence in superovulated rats. Postnatal day (PND) 22 rats were treated with potassium dichromate (1 and 5 ppm) in drinking water from PND 22-29 and superovulated. MII oocytes were analyzed by immunofluorescence, and images were captured by confocal microscopy and quantified by Image-Pro Plus software, Version 10.0.5. Our data showed that Cr(VI) increased microtubule misalignment (similar to 9 fold), led to missegregation of chromosomes and bulged and folded actin caps, increased oxidative DNA (similar to 3 fold) and protein (similar to 9-12 fold) damage, and increased DNA double-strand breaks (similar to 5-10 fold) and DNA repair protein RAD51 (similar to 3-6 fold). Cr(VI) also induced incomplete cytokinesis and delayed polar body extrusion. Our study indicates that exposure to environmentally relevant doses of Cr(VI) caused severe DNA damage, distorted oocyte cytoskeletal proteins, and caused oxidative DNA and protein damage, resulting in developmental arrest in MII oocytes.
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