2. Academic Validation
  3. Eicosatrienoic acid enhances the quality of in vitro matured porcine oocytes by reducing PRKN-mediated ubiquitination of CISD2

Eicosatrienoic acid enhances the quality of in vitro matured porcine oocytes by reducing PRKN-mediated ubiquitination of CISD2

  • Theriogenology. 2024 Dec:230:285-298. doi: 10.1016/j.theriogenology.2024.09.020.
Zhi-Yong An 1,  Sheng-Zhong Han 2,  Zhou-Yan Li 3,  Shuang-Yan Chang 4,  Xiu-Li Zhang 5,  Gao-Jie Lu 6,  Tuo Zhang 7,  Biao-Hu Quan 8,  Xi-Jun Yin 9,  Lin-Hu Quan 10,  Jin-Dan Kang 11
Affiliations

Affiliations

  • 1 Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China. Electronic address: 56245398@qq.com.
  • 2 Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China. Electronic address: 1220844861@qq.com.
  • 3 Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China. Electronic address: lizhouyan9@qq.com.
  • 4 Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China. Electronic address: 457581236@qq.com.
  • 5 Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China. Electronic address: 1612308913@qq.com.
  • 6 Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China. Electronic address: lgj1904406294@163.com.
  • 7 Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China. Electronic address: 2911713681@qq.com.
  • 8 Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China; Jilin Provincial Key Laboratory of Transgenic Animal and Embryo Engineering, Yanji, 133002, China. Electronic address: 0000008591@ybu.edu.cn.
  • 9 Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China; Jilin Provincial Key Laboratory of Transgenic Animal and Embryo Engineering, Yanji, 133002, China. Electronic address: Yinxijun@ybu.edu.cn.
  • 10 College of Pharmacy, Yanbian University, Yanji, 133002, China. Electronic address: lhquan@ybu.edu.cn.
  • 11 Department of Animal Science, College of Agriculture, Yanbian University, Yanji, 133002, China; Jilin Provincial Key Laboratory of Transgenic Animal and Embryo Engineering, Yanji, 133002, China. Electronic address: jdkang@ybu.edu.cn.
PMID: 39357167 DOI: 10.1016/j.theriogenology.2024.09.020
Abstract

Oocytes and early embryos are exposed to many uncontrollable factors that trigger endoplasmic reticulum (ER) stress during in vitro culture. Prevention of ER stress is an effective way to improve the oocyte maturation rate and oocyte quality. Increasing evidence suggests that dietary intake of sufficient n-3 polyunsaturated fatty acids (PUFAs) is associated with health benefits, particularly in the domain of female reproductive health. We found that supplementation of eicosatrienoic acid (ETA) during in vitro maturation (IVM) of oocyte significantly downregulated ER stress-related genes. Mitochondria-associated membranes (MAMs) are communications areas between the ER and mitochondria. Inositol 1,4,5-trisphosphate receptor (IP3R) is a key calcium channels in MAMs and, participates in the regulation of many cellular functions. Notably, the MAM area was significantly decreased in ETA-treated oocytes. CDGSH iron sulfur domain 2 (CISD2) is presents in MAMs, but its role in oocytes is unknown. ETA treatment significantly increased CISD2 expression, and siRNA-mediated knockdown of CISD2 blocked the inhibitory effect of ETA on IP3R. Transcriptomic Sequencing and immunoprecipitation experiments showed that ETA treatment significantly decreased expression of the E3 ubiquitin Ligase PRKN. PRKN induced ubiquitination and degradation of CISD2, indicating that the PRKN-mediated ubiquitin-proteasome system regulates CISD2. In conclusion, our study reveals the mechanism by which ETA supplementation during IVM alleviates mitochondrial calcium overload under ER stress conditions by decreasing PRKN-mediated ubiquitination of CISD2 and facilitating inhibition of IP3R by CISD2/Bcl-2. This improves oocyte quality and subsequent embryo developmental competence prior to implantation.

Keywords

Calcium; ETA; Endoplasmic reticulum stress; IP3R; MAM; Ubiquitin.

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