Combined effect of unfolded protein response and circZc3h4, circRNA Scar in mouse ovary and uterus damage induced by procymidone

Li, Rui; Xin, Bingyan; Wang, Qing; Wang, Zhen; Fu, Haidong; Yan, Zhengli; Zhu, Yongfei

doi:10.1016/j.ecoenv.2021.113068

Cited by 6 publications

(14 citation statements)

References 40 publications

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“…This may be due to the estrogen-like effect of Cd 2+ and the antiandrogenic effect of PCM, 2,3 which can reduce E2 and P levels. 4,22 Their combined effect may be resulting in impaired development and reduced follicle numbers at all stages of the organism. This effect was not only significantly more intense than that of individual Cd 2+ and PCM, but it also showed a doseresponse relationship.…”

Section: Discussionmentioning

confidence: 99%

“…Ovarian blocks used for culture were randomized into six groups, and Cd 2+ and/or PCM were added to the medium of each treatment group as follows: 0.1% (V/V) acetone + 8. 4 for the high dose (H+PCM) group; and 0.1% (V/V) acetone for the control (C) group. The main components of the ovarian medium were Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM/F12) medium, 10% fetal bovine serum, 1% penicillin-streptomycin, 1% ascorbic acid, and 1% albumin.…”

Section: In Vitro Three-dimensional Culture Of Ovariesmentioning

confidence: 99%

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Low levels of Cd²⁺ combined with procymidone may cause ovarian damage in mice via unfolded protein response

Li,

Wang,

Zhang

et al. 2024

Environmental Toxicology

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As no study about the combined effect of low levels of Cd2+ with procymidone (PCM) on organs and organisms, we investigated their actions on mouse‐ovary in vivo and in vitro. Four‐week mice were treated with corn oil for the control group, corn oil + 0.0045 mg/L Cd2+ (CdCl2 was dissolved in ultrapure water and freely consumed by mice) for Cd2+ group, 50 mg/kg/d PCM (suspended in corn oil and administered orally to mice) for PCM group, and 50 mg/kg/d PCM + 0.0015 (0.0045 and 0.0135) mg/L Cd2+ for L+ (M+ and H+) PCM group for 21 days. For in vitro experiment, the cultured ovaries were treated with acetone for the control group, 0.1% acetone + 8.4 μg/L Cd2+ for the Cd2+ group, 0.63 mg/L PCM (dissolved in acetone) for the PCM‐group, and 0.63 mg/L PCM + 2.8 (8.4 and 25.2) μg/L Cd2+ for L+ (M+ and H+) PCM group for 7 days. Mouse body weight in each treatment group, the weight and volume of ovaries in all PCM groups were lower than the control. Both in vivo and in vitro, all‐stage follicle numbers were lower in M+PCM and H+PCM groups, whereas the atretic follicles and CASPASE3/8 were higher; meanwhile, lower estradiol and progesterone and higher unfolded protein response (UPR) members in all PCM groups. L+, M+, and H+PCM groups had further ovarian damage and stronger UPR than PCM groups, as did M+PCM groups over Cd2+ groups. It is hypothesized low‐level PCM and Cd2+ may mutually promote each other's triggered UPR and exacerbate ovarian damage.

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Section: Discussionmentioning

confidence: 99%

Section: In Vitro Three-dimensional Culture Of Ovariesmentioning

confidence: 99%

Low levels of Cd²⁺ combined with procymidone may cause ovarian damage in mice via unfolded protein response

Li,

Wang,

Zhang

et al. 2024

Environmental Toxicology

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“…Uterus and ovary Uterus and ovary injury circZC3H4 downregulated Promotes cell apoptosis [141] circScar upregulated Inhibits cell proliferation [141] Page 10 of 23 patient's blood samples and mice models, the study identified an upregulation of circ-FOXO3 expression level during brain I/RI. Further analyses of circFOXO3 showed that by interacting with mTOR and E2F1, circFOXO3 was able to inhibit mTORC1 activity.…”

Section: Types Of Injury Circrna Expression Pattern Downstream Regula...mentioning

confidence: 94%

“…Using in vivo mouse models, Li et al reported a significant upregulation in circScar expression and a significant downregulation in circZC3H4 expression upon procymidone dose-dependent uterus and ovary damage [141]. The former, circScar, has been previously reported to quench ATP synthase β-subunit (ATP5B) [142], leading to inhibition of ATP production and subsequent ovarian cell proliferation [143].…”

Section: Reproductive System: Uterus and Ovary Injurymentioning

confidence: 99%

Circular RNAs in organ injury: recent development

et al. 2022

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Circular ribonucleic acids (circRNAs) are a class of long non-coding RNA that were once regarded as non-functional transcription byproducts. However, recent studies suggested that circRNAs may exhibit important regulatory roles in many critical biological pathways and disease pathologies. These studies have identified significantly differential expression profiles of circRNAs upon changes in physiological and pathological conditions of eukaryotic cells. Importantly, a substantial number of studies have suggested that circRNAs may play critical roles in organ injuries. This review aims to provide a summary of recent studies on circRNAs in organ injuries with respect to (1) changes in circRNAs expression patterns, (2) main mechanism axi(e)s, (3) therapeutic implications and (4) future study prospective. With the increasing attention to this research area and the advancement in high-throughput nucleic acid sequencing techniques, our knowledge of circRNAs may bring fruitful outcomes from basic and clinical research.

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“…According to the report of the Joint Meeting of Food and Agriculture Organization of the United Nations (FAO) and World Health Organization (WHO) on Pesticide Residues (JMPR), the no observed adverse effect level (NOAEL) in the human body of PCM is 100 mg/kg/day 15 . However, we previously found that long‐term exposure of adolescent female mice to PCM below this standard dose is still likely to damage the ovaries and uteri of mice, 16 so in this study, we attempted to explore the joint actions of UPR, circZc3h4, and circRNA Scar in testicular injuries in adolescent mice, and hence to understand the molecular biological mechanism of PCM‐induced testicular injury in mice.…”

Section: Introductionmentioning

confidence: 99%

The joint action of unfolded protein response, circZc3h4, and circRNA Scar in procymidone‐induced testicular injury in adolescent mice

Xin

et al. 2022

Environmental Toxicology

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Procymidone (PCM) is a low toxicity fungicide, and an endocrine‐disrupting chemical (EDC) that particularly damages the reproductive system of male vertebrates. In present study, adolescent mice in control, low‐, medium‐, and high‐dose groups were orally administered 0 (equal volume of soybean oil), 50, 100, and 200 mg/kg/day PCM, respectively, for 21 days. Additionally, a three‐dimensional culture of mouse testes was performed in vitro, and the control, low dose (0.33 × 10−5 M), medium dose (1 × 10−5 M), and high dose (3 × 10−5 M) PCM groups were established. We have found that, under both in vivo and in vitro conditions, all doses of PCM caused damage to mouse testes. Moreover, the levels of circZc3h4 RNA and Zc3h4 decreased while miR‐212 increased in all treatment groups, with a corresponding rise in circRNA Scar and fall in Atp5b, compared to those in the control group, and all the changes showed a dose–response relationship. Besides, we have identified that low doses of PCM could activate the Ire1‐Xbp1 pathway, whereas the medium and high doses activated the Perk‐Elf2α‐Atf4, Ire1‐Xbp1, and Atf6 pathways. And it is, therefore, speculated that the unfolded protein response (UPR), circZc3h4 and circRNA Scar may have taken joint action in testicular injury in adolescent mice induced by PCM at the no observed adverse effect level (NOAEL, 100 mg/kg/day) and below NOAEL doses.

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Combined effect of unfolded protein response and circZc3h4, circRNA Scar in mouse ovary and uterus damage induced by procymidone

Cited by 6 publications

References 40 publications

Low levels of Cd²⁺ combined with procymidone may cause ovarian damage in mice via unfolded protein response

Low levels of Cd²⁺ combined with procymidone may cause ovarian damage in mice via unfolded protein response

Circular RNAs in organ injury: recent development

The joint action of unfolded protein response, circZc3h4, and circRNA Scar in procymidone‐induced testicular injury in adolescent mice

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Combined effect of unfolded protein response and circZc3h4, circRNA Scar in mouse ovary and uterus damage induced by procymidone

Cited by 6 publications

References 40 publications

Low levels of Cd2+ combined with procymidone may cause ovarian damage in mice via unfolded protein response

Low levels of Cd2+ combined with procymidone may cause ovarian damage in mice via unfolded protein response

Circular RNAs in organ injury: recent development

The joint action of unfolded protein response, circZc3h4, and circRNA Scar in procymidone‐induced testicular injury in adolescent mice

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Low levels of Cd²⁺ combined with procymidone may cause ovarian damage in mice via unfolded protein response

Low levels of Cd²⁺ combined with procymidone may cause ovarian damage in mice via unfolded protein response