Environmental copper exposure, placental cuproptosis, and miscarriage
Copyright © 2024 Elsevier Ltd. All rights reserved..
Copper pollution has become global environmental concern. Widespread Cu pollution results in excessive Cu exposure in human. Epidemiological studies and animal experiments revealed that Cu exposure might have reproductive toxicity. Cuproptosis is a newly reported Cu-dependent and programmed cell death formTsvetkov et al., 2022. However, whether copper exposure at real environmental exposure dose might cause placental cuproptosis and induce miscarriage was completely unexplored. In this study, we found that Cu exposure during pregnancy induced miscarriage or complete pregnancy loss by inducing placenta cuproptosis in CuCl2-exposed pregnant mice. Notably, Cu exposure at 1.3 mg/kg/d (a real environmental exposure dose) was enough to cause placenta cuproptosis. CuCl2 exposure disrupts the TCA cycle, causes proteotoxic stress, increases Cu2+ ion import/decreases Cu2+ export, and results in the loss of Fe-S cluster proteins in mouse placenta, which induces placenta cuproptosis. Moreover, we also identified that Cu exposure down-regulates the expression levels of mmu-miR-3473b, which interacts with Dlst or Rtel1 mRNA and simultaneously positively regulates Dlst or Rtel1 expression, thereby disrupting the TCA cycle and resulting in the loss of Fe-S cluster proteins, and thus epigenetically regulates placental cuproptosis. Treatment with TTM (a cuproptosis inhibitor) suppressed placental cuproptosis and alleviated miscarriage in CuCl2-exposed mice. This work provides novel reproductive toxicity of Cu exposure in miscarriage or complete pregnancy loss by causing placental cuproptosis. This study also provides new ways for further studies on other toxicological effects of Cu and proposes a new approach for protection against Cu-induced reproductive diseases.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:348 |
|---|---|
| Enthalten in: |
Environmental pollution (Barking, Essex : 1987) - 348(2024) vom: 01. Apr., Seite 123847 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zhao, Jingsong [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
789U1901C5 |
|---|
| Anmerkungen: |
Date Completed 22.04.2024 Date Revised 22.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.envpol.2024.123847 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370422953 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370422953 | ||
| 003 | DE-627 | ||
| 005 | 20240422232329.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240331s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.envpol.2024.123847 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1383.xml |
| 035 | |a (DE-627)NLM370422953 | ||
| 035 | |a (NLM)38552771 | ||
| 035 | |a (PII)S0269-7491(24)00561-X | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Zhao, Jingsong |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Environmental copper exposure, placental cuproptosis, and miscarriage |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 22.04.2024 | ||
| 500 | |a Date Revised 22.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier Ltd. All rights reserved. | ||
| 520 | |a Copper pollution has become global environmental concern. Widespread Cu pollution results in excessive Cu exposure in human. Epidemiological studies and animal experiments revealed that Cu exposure might have reproductive toxicity. Cuproptosis is a newly reported Cu-dependent and programmed cell death formTsvetkov et al., 2022. However, whether copper exposure at real environmental exposure dose might cause placental cuproptosis and induce miscarriage was completely unexplored. In this study, we found that Cu exposure during pregnancy induced miscarriage or complete pregnancy loss by inducing placenta cuproptosis in CuCl2-exposed pregnant mice. Notably, Cu exposure at 1.3 mg/kg/d (a real environmental exposure dose) was enough to cause placenta cuproptosis. CuCl2 exposure disrupts the TCA cycle, causes proteotoxic stress, increases Cu2+ ion import/decreases Cu2+ export, and results in the loss of Fe-S cluster proteins in mouse placenta, which induces placenta cuproptosis. Moreover, we also identified that Cu exposure down-regulates the expression levels of mmu-miR-3473b, which interacts with Dlst or Rtel1 mRNA and simultaneously positively regulates Dlst or Rtel1 expression, thereby disrupting the TCA cycle and resulting in the loss of Fe-S cluster proteins, and thus epigenetically regulates placental cuproptosis. Treatment with TTM (a cuproptosis inhibitor) suppressed placental cuproptosis and alleviated miscarriage in CuCl2-exposed mice. This work provides novel reproductive toxicity of Cu exposure in miscarriage or complete pregnancy loss by causing placental cuproptosis. This study also provides new ways for further studies on other toxicological effects of Cu and proposes a new approach for protection against Cu-induced reproductive diseases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cu or copper pollution | |
| 650 | 4 | |a Cuproptosis | |
| 650 | 4 | |a Miscarriage and pregnancy loss | |
| 650 | 4 | |a Mouse placenta | |
| 650 | 4 | |a miRNA | |
| 650 | 7 | |a Copper |2 NLM | |
| 650 | 7 | |a 789U1901C5 |2 NLM | |
| 700 | 1 | |a Xu, Zhongyan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiaoqing |e verfasserin |4 aut | |
| 700 | 1 | |a Wan, Shukun |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Weina |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Wenxin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Manli |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Rong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Huidong |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Environmental pollution (Barking, Essex : 1987) |d 1987 |g 348(2024) vom: 01. Apr., Seite 123847 |w (DE-627)NLM087741504 |x 1873-6424 |7 nnns |
| 773 | 1 | 8 | |g volume:348 |g year:2024 |g day:01 |g month:04 |g pages:123847 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.envpol.2024.123847 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 348 |j 2024 |b 01 |c 04 |h 123847 | ||