T-2 toxin exposure induces ovarian damage in sows: lncRNA CUFF.253988.1 promotes cell apoptosis by inhibiting the SIRT3/PGC1α pathway.
Ecotoxicol Environ Saf
; 283: 116787, 2024 Sep 15.
Article
in En
| MEDLINE
| ID: mdl-39067079
ABSTRACT
T-2 toxin, a mycotoxin found in foods and feeds, poses a threat to female reproductive health in both humans and animals. LncRNA CUFF.253988.1 (CUFF.253988.1), highly expressed in pigs, has an undisclosed regulatory role. This study aimed to establish a model of T-2 toxin-induced ovarian injury in sows, both in vivo and in vitro, and to explore the regulatory role and potential mechanisms of CUFF.253988.1. The results showed that feeding T-2 toxin-contaminated feed (1â¯mg/kg) induced ovarian follicle atresia and mitochondrial structural damage, accompanied by a significant upregulation of CUFF.253988.1 expression in the ovaries. Additionally, T-2 toxin inhibited the SIRT3/PGC1-α pathway associated with mitochondrial function. Moreover, T-2 toxin induced cell apoptosis by upregulating the expression of Cyt c, Bax, cleaved-caspase-9, and cleaved-caspase-3 proteins. In T-2 toxin-induced injury to the ovarian granulosa AVG-16 cells at concentrations of 10, 40 and 160â¯nM, not only were the previously mentioned effects observed, but also a decrease in mitochondrial membrane potential, ATP content, and an elevation in ROS levels. However, downregulating CUFF.253988.1 reversed T-2 toxin's inhibition of the SIRT3/PGC1-α pathway, alleviating mitochondrial dysfunction and reducing cell apoptosis. Notably, this may be attributed to the inhibition of T-2 toxin-induced enrichment of CUFF.253988.1 in mitochondria. In conclusion, CUFF.253988.1 plays a pivotal role in T-2 toxin-induced ovarian damage, operating through the inhibition of the SIRT3/PGC1-α pathway and promotion of cell apoptosis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ovary
/
T-2 Toxin
/
Apoptosis
/
Sirtuin 3
/
RNA, Long Noncoding
/
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Limits:
Animals
Language:
En
Journal:
Ecotoxicol Environ Saf
/
Ecotoxicol. environ. saf
/
Ecotoxicology and environmental safety
Year:
2024
Document type:
Article
Country of publication:
Netherlands