Gestational exposure to arsenic reduces female offspring fertility by impairing the repair of DNA double-strand breaks and synapsis formation in oocytes

Arsenic is a pollutant that can cross the placenta; however, research on the effects of arsenic exposure during pregnancy on the fertility of female offspring is limited. To address this gap, we developed a mouse model to investigate the relationship between arsenic exposure during pregnancy and fer...

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Main Authors: Cong Ma, Kaiqin Hu, Xueke Zhang, Yaru Yu, Zuying Xu, Tian Ma, Hongzhen Ruan, Yingying Zhang, Jiajia Wang, Xinyu Yue, Chunmei Liang, Huifen Xiang, Rui Guo, Yunxia Cao, Zhiming Ding
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651324015549
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author Cong Ma
Kaiqin Hu
Xueke Zhang
Yaru Yu
Zuying Xu
Tian Ma
Hongzhen Ruan
Yingying Zhang
Jiajia Wang
Xinyu Yue
Chunmei Liang
Huifen Xiang
Rui Guo
Yunxia Cao
Zhiming Ding
author_facet Cong Ma
Kaiqin Hu
Xueke Zhang
Yaru Yu
Zuying Xu
Tian Ma
Hongzhen Ruan
Yingying Zhang
Jiajia Wang
Xinyu Yue
Chunmei Liang
Huifen Xiang
Rui Guo
Yunxia Cao
Zhiming Ding
author_sort Cong Ma
collection DOAJ
description Arsenic is a pollutant that can cross the placenta; however, research on the effects of arsenic exposure during pregnancy on the fertility of female offspring is limited. To address this gap, we developed a mouse model to investigate the relationship between arsenic exposure during pregnancy and fertility in female offspring. Our fertility assessment revealed that gestational exposure to 1 mg/kg arsenic or higher (10 mg/kg) resulted in reduction in litter size, ovarian volume, and multistage-follicle number in female offspring. By assessing the in vitro developmental capacity of oocytes and zygotes, we confirmed that the reduced fertility was due not to impaired oocyte quality but rather to a reduction in oocyte quantity. Arsenic exposure impedes synapsis formation in MPI and compromises homologous recombination-mediated repair of double-strand breaks, resulting in fewer crossovers. This disruption activates the pachytene-checkpoint, hindering the progression of the MPI and resulting in the elimination of defective oocytes through p-Chk2 activation. Our study reveals for the first time the detrimental effects of arsenic exposure during pregnancy on the fertility of female offspring, underscoring the urgent need to prevent such exposure to safeguard reproductive health.
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spelling doaj-art-e24fac2fdcf64f0c9f3182039e4b5b122025-01-23T05:25:43ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117478Gestational exposure to arsenic reduces female offspring fertility by impairing the repair of DNA double-strand breaks and synapsis formation in oocytesCong Ma0Kaiqin Hu1Xueke Zhang2Yaru Yu3Zuying Xu4Tian Ma5Hongzhen Ruan6Yingying Zhang7Jiajia Wang8Xinyu Yue9Chunmei Liang10Huifen Xiang11Rui Guo12Yunxia Cao13Zhiming Ding14Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, ChinaNHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People’s Republic of China, No. 81 Meishan Road, Hefei 230032, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China; Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No. 81 Meishan Road, Hefei, Anhui 230032, China; Corresponding authors at: Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, China.Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People’s Republic of China, No. 81 Meishan Road, Hefei 230032, China; Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No. 81 Meishan Road, Hefei, Anhui 230032, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No. 81 Meishan Road, Hefei 230032, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China; Anhui Provincial Institute of Translational Medicine, No. 81 Meishan Road, Hefei 230032, China; Corresponding authors at: Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, China.Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People’s Republic of China, No. 81 Meishan Road, Hefei 230032, China; Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No. 81 Meishan Road, Hefei, Anhui 230032, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No. 81 Meishan Road, Hefei 230032, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, China; Anhui Provincial Institute of Translational Medicine, No. 81 Meishan Road, Hefei 230032, China; Corresponding authors at: Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, China.Arsenic is a pollutant that can cross the placenta; however, research on the effects of arsenic exposure during pregnancy on the fertility of female offspring is limited. To address this gap, we developed a mouse model to investigate the relationship between arsenic exposure during pregnancy and fertility in female offspring. Our fertility assessment revealed that gestational exposure to 1 mg/kg arsenic or higher (10 mg/kg) resulted in reduction in litter size, ovarian volume, and multistage-follicle number in female offspring. By assessing the in vitro developmental capacity of oocytes and zygotes, we confirmed that the reduced fertility was due not to impaired oocyte quality but rather to a reduction in oocyte quantity. Arsenic exposure impedes synapsis formation in MPI and compromises homologous recombination-mediated repair of double-strand breaks, resulting in fewer crossovers. This disruption activates the pachytene-checkpoint, hindering the progression of the MPI and resulting in the elimination of defective oocytes through p-Chk2 activation. Our study reveals for the first time the detrimental effects of arsenic exposure during pregnancy on the fertility of female offspring, underscoring the urgent need to prevent such exposure to safeguard reproductive health.http://www.sciencedirect.com/science/article/pii/S0147651324015549MetalloidReproduction and mammalMeiotic prophase IHomologous recombination
spellingShingle Cong Ma
Kaiqin Hu
Xueke Zhang
Yaru Yu
Zuying Xu
Tian Ma
Hongzhen Ruan
Yingying Zhang
Jiajia Wang
Xinyu Yue
Chunmei Liang
Huifen Xiang
Rui Guo
Yunxia Cao
Zhiming Ding
Gestational exposure to arsenic reduces female offspring fertility by impairing the repair of DNA double-strand breaks and synapsis formation in oocytes
Ecotoxicology and Environmental Safety
Metalloid
Reproduction and mammal
Meiotic prophase I
Homologous recombination
title Gestational exposure to arsenic reduces female offspring fertility by impairing the repair of DNA double-strand breaks and synapsis formation in oocytes
title_full Gestational exposure to arsenic reduces female offspring fertility by impairing the repair of DNA double-strand breaks and synapsis formation in oocytes
title_fullStr Gestational exposure to arsenic reduces female offspring fertility by impairing the repair of DNA double-strand breaks and synapsis formation in oocytes
title_full_unstemmed Gestational exposure to arsenic reduces female offspring fertility by impairing the repair of DNA double-strand breaks and synapsis formation in oocytes
title_short Gestational exposure to arsenic reduces female offspring fertility by impairing the repair of DNA double-strand breaks and synapsis formation in oocytes
title_sort gestational exposure to arsenic reduces female offspring fertility by impairing the repair of dna double strand breaks and synapsis formation in oocytes
topic Metalloid
Reproduction and mammal
Meiotic prophase I
Homologous recombination
url http://www.sciencedirect.com/science/article/pii/S0147651324015549
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