Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan 18;45(1):176-188.
doi: 10.24272/j.issn.2095-8137.2023.032.

Endogenous biosynthesis of docosahexaenoic acid (DHA) regulates fish oocyte maturation by promoting pregnenolone production

Yi Li  1   2 , Xuehui Li  1   2 , Ding Ye  1   2 , Ru Zhang  1   2 , Chengjie Liu  1   2 , Mudan He  1   2 , Houpeng Wang  1   2 , Wei Hu  1   2   3 , Yonghua Sun  1   2   4
Affiliations

Endogenous biosynthesis of docosahexaenoic acid (DHA) regulates fish oocyte maturation by promoting pregnenolone production

Yi Li et al. Zool Res. .

Abstract
in English, Chinese

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), particularly docosahexaenoic acid (22:6n-3, DHA), play crucial roles in the reproductive health of vertebrates, including humans. Nevertheless, the underlying mechanism related to this phenomenon remains largely unknown. In this study, we employed two zebrafish genetic models, i.e., elovl2 -/- mutant as an endogenous DHA-deficient model and fat1 (omega-3 desaturase encoding gene) transgenic zebrafish as an endogenous DHA-rich model, to investigate the effects of DHA on oocyte maturation and quality. Results show that the elovl2 -/- mutants had much lower fecundity and poorer oocyte quality than the wild-type controls, while the fat1 zebrafish had higher fecundity and better oocyte quality than wild-type controls. DHA deficiency in elovl2 -/- embryos led to defects in egg activation, poor microtubule stability, and reduced pregnenolone levels. Further study revealed that DHA promoted pregnenolone synthesis by enhancing transcription of cyp11a1, which encodes the cholesterol side-chain cleavage enzyme, thereby stabilizing microtubule assembly during oogenesis. In turn, the hypothalamic-pituitary-gonadal axis was enhanced by DHA. In conclusion, using two unique genetic models, our findings demonstrate that endogenously synthesized DHA promotes oocyte maturation and quality by promoting pregnenolone production via transcriptional regulation of cyp11a1.

众多的证据表明，omega-3多不饱和脂肪酸（n-3 PUFAs），尤其是二十二碳六烯酸（22:6n-3, DHA）对包括人类在内的脊椎动物的生殖健康具有重要作用。然而，这一现象背后的调控机制在很大程度上仍属未知。该研究以DHA合成缺陷的脂肪酸延长酶 elovl2突变（ elovl2 -/- ）斑马鱼和内源DHA合成增强的omega-3去饱和酶编码基因（ fat1）转基因斑马鱼，分别作为DHA内源合成缺陷和增强模型，系统研究了内源合成的DHA在调控脊椎动物卵母细胞成熟和卵子质量中的作用及其作用机制。研究发现， elovl2 -/- 突变雌性斑马鱼的繁殖力和卵子质量显著低于野生型（WT）斑马鱼，而 fat1转基因雌性斑马鱼的繁殖力和卵子质量均高于WT斑马鱼。 elovl2 -/- 胚胎因缺乏内源DHA导致卵子激活缺陷、微管稳定性较差和孕烯醇酮（pregnenolone， P5）水平降低。进一步研究发现，内源合成的DHA通过促进胆固醇侧链裂解酶编码基因 cyp11a1的转录来促进P5的合成，从而在卵子发生过程中稳定微管组装和细胞骨架；DHA反过来则进一步促进了下丘脑-垂体-性腺（hypothalamic–pituitary–gonadal，HPG）轴的活性。总之，通过DHA合成缺陷和合成增强的斑马鱼模型，这项研究揭示了内源性合成的DHA在卵巢中通过对 cyp11a1转录调节促进P5的产生，进而促进卵母细胞成熟并提升卵子质量的新机制。.

Keywords: Docosahexaenoic acid; Microtubule; Oocyte maturation; Oocyte quality; Pregnenolone.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
DHA is important for oocyte maturation and successful fertilization
Figure 2
Figure 2
DHA promotes oocyte quality
Figure 3
Figure 3
DHA promotes oocyte quality through production of pregnenolone
Figure 4
Figure 4
DHA regulates transcription of cyp11a1 and activates HPG axis
Figure 5
Figure 5
fat1 transgene restores fecundity of elovl2-/- mutant
Figure 6
Figure 6
Graphic summary of role of DHA in oocyte maturation and oocyte quality
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Agarwal A, Aponte-Mellado A, Premkumar BJ, et al The effects of oxidative stress on female reproduction: a review. Reproductive Biology and Endocrinology. 2012;10:49. doi: 10.1186/1477-7827-10-49. - DOI - PMC - PubMed
    1. Akhmanova A, Steinmetz MO Control of microtubule organization and dynamics: two ends in the limelight. Nature Reviews Molecular Cell Biology. 2015;16(12):711–726. doi: 10.1038/nrm4084. - DOI - PubMed
    1. Arita M, Bianchini F, Aliberti J, et al Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. Journal of Experimental Medicine. 2005;201(5):713–722. doi: 10.1084/jem.20042031. - DOI - PMC - PubMed
    1. Arita M, Ohira T, Sun YP, et al Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. The Journal of Immunology. 2007;178(6):3912–3917. doi: 10.4049/jimmunol.178.6.3912. - DOI - PubMed
    1. Cerri RLA, Juchem SO, Chebel RC, et al Effect of fat source differing in fatty acid profile on metabolic parameters, fertilization, and embryo quality in high-producing dairy cows. Journal of Dairy Science. 2009;92(4):1520–1531. doi: 10.3168/jds.2008-1614. - DOI - PubMed

Substances

LinkOut - more resources