Endogenous biosynthesis of docosahexaenoic acid (DHA) regulates fish oocyte maturation by promoting pregnenolone production
Yi Li, 中国科学院水生生物研究所种子设计创新研究院淡水生态与生物技术国家重点实验室, 湖北 武汉 430072, 中国, Xuehui Li, Ye Ding, Ru Zhang, Chengjie Liu, Mudan He, Houpeng Wang, Wei Hu, Yonghua Sun, 中国科学院大学现代农业科学学院, 北京 100049, 中国, 湖北洪山实验室, 湖北 武汉430070, 中国
Abstract
Omega-3 polyunsaturated fatty acids (n-3 PUFAs), particularly docosahexaenoic acid (22:6n-3, DHA), have been shown to play a crucial role in reproduction and reproductive health of vertebrates, including humans. However, the underlying mechanism of this phenomenon remains largely unknown. In this study, we used two zebrafish genetic models, the elovl2-/- mutant as an endogenous DHA-deficient model and the fat1 (an omega-3 desaturase encoding gene) transgenic zebrafish as an endogenous DHA-rich model, to investigate the effects of DHA on oocyte maturation and oocyte quality. Our results show that the elovl2-/- mutant zebrafish had much lower fecundity and poorer oocyte quality than the wildtype controls, while the fat1 zebrafish had higher fecundity and better oocyte quality than wildtype controls. DHA deficiency in elovl2-/- embryos led to defects of egg activation, poor microtubule stability and reduced pregnenolone levels. Further study reveals that DHA promotes pregnenolone synthesis by promoting the transcription of cyp11a1, which encodes the cholesterol side-chain cleavage enzyme, thereby stabilizing microtubule assembly during oogenesis. In turn, the hypothalamic–pituitary–gonadal (HPG) axis is enhanced by DHA. In conclusion, using two unique genetic models, our study demonstrates the endogenously synthesized DHA promotes oocyte maturation and oocyte quality by promoting pregnenolone production via transcriptional regulation of cyp11a1.