Reduction of Oocyte Lipid Droplets and Meiotic Failure Due to Biotin Deficiency Was Not Rescued by Restoring the Biotin Nutritional Status

Overview

Journal Nutr Res Pract

Specialty Nutritional Sciences

Date 2022 Jun 6

PMID 35663441

Authors

Ai Tsuji

Yuka Ikeda

Mutsumi Murakami

Yasuko Kitagishi

Satoru Matsuda

Affiliations

Soon will be listed here.

Abstract

Background/objectives: Oocyte lipid droplets play a crucial role in meiosis and embryo development. Biotin is associated with fatty acid synthesis and is the coenzyme for acetyl-CoA carboxylase (ACC). The effects of a biotin deficiency on the oocyte lipid metabolism remain unknown. This study examined the effects of a biotin deficiency and its replenishment on murine 1) oocyte lipid droplet levels, 2) ovary lipid metabolism, and 3) oocyte meiosis.

Materials/methods: Mice were divided into 3 groups: control, biotin deficient (BD), and recovery groups. The control and BD groups were fed a control diet or BD diet (0.004 or 0 g biotin/kg), respectively. The recovery group mice were fed a BD diet until day 21, and were then fed the control diet from days 22 to 64. This study then quantified the oocyte lipid droplet levels, assessed the oocyte mitochondrial function, and examined the ability of oocytes to undergo meiosis. Ovarian phosphorylated ACC (p-ACC), lipogenesis, β-oxidation, and ATP production-related genes were evaluated.

Results: The BD group showed a decrease in lipid droplets and mitochondrial membrane potential and increased p-ACC levels. In the recovery group, the hepatic biotin concentration, ovarian p-ACC levels, and mitochondrial membrane potential were restored to the control group levels. On the other hand, the quantity of lipid droplets in the recovery group was not restored to the control levels. Furthermore, the percentage of oocytes with meiotic abnormalities was higher in the recovery group than in the control group.

Conclusions: A biotin deficiency reduced the oocyte lipid droplet levels by downregulating lipogenesis. The decreased lipid droplets and increased oocyte meiosis failure were not fully restored, even though the biotin nutrition status and gene expression of lipid metabolism was resumed. These results suggest that a biotin deficiency remains robust and can be long-lasting. Biotin might play a crucial role in maintaining the oocyte quality.

References

Hassold T, Chiu D . Maternal age-specific rates of numerical chromosome abnormalities with special reference to trisomy. Hum Genet. 1985; 70(1):11-7. DOI: 10.1007/BF00389450. View

Selvam S, Ramaian Santhaseela A, Ganesan D, Rajasekaran S, Jayavelu T . Autophagy inhibition by biotin elicits endoplasmic reticulum stress to differentially regulate adipocyte lipid and protein synthesis. Cell Stress Chaperones. 2019; 24(2):343-350. PMC: 6439007. DOI: 10.1007/s12192-018-00967-9. View

Hernandez-Vazquez A, Wolf B, Pindolia K, Ortega-Cuellar D, Hernandez-Gonzalez R, Heredia-Antunez A . Biotinidase knockout mice show cellular energy deficit and altered carbon metabolism gene expression similar to that of nutritional biotin deprivation: clues for the pathogenesis in the human inherited disorder. Mol Genet Metab. 2013; 110(3):248-54. DOI: 10.1016/j.ymgme.2013.08.018. View

Suchy S, Rizzo W, Wolf B . Effect of biotin deficiency and supplementation on lipid metabolism in rats: saturated fatty acids. Am J Clin Nutr. 1986; 44(4):475-80. DOI: 10.1093/ajcn/44.4.475. View

Fennelly J, Frank O, Baker H, Leevy C . PERIPHERAL NEUROPATHY OF THE ALCOHOLIC: I, AETIOLOGICAL ROLE OF ANEURIN AND OTHER B-COMPLEX VITAMINS. Br Med J. 1964; 2(5420):1290-2. PMC: 1817403. DOI: 10.1136/bmj.2.5420.1290. View

Regueira M, Riera M, Galardo M, Camberos M, Pellizzari E, Cigorraga S . FSH and bFGF regulate the expression of genes involved in Sertoli cell energetic metabolism. Gen Comp Endocrinol. 2015; 222:124-33. DOI: 10.1016/j.ygcen.2015.08.011. View

Gorbsky G, Simerly C, Schatten G, Borisy G . Microtubules in the metaphase-arrested mouse oocyte turn over rapidly. Proc Natl Acad Sci U S A. 1990; 87(16):6049-53. PMC: 54469. DOI: 10.1073/pnas.87.16.6049. View

Tsuji A, Nakamura T, Shibata K . Biotin-deficient diet induces chromosome misalignment and spindle defects in mouse oocytes. Biosci Biotechnol Biochem. 2014; 79(2):292-9. DOI: 10.1080/09168451.2014.968090. View

Wolf B . Biotinidase deficiency and our champagne legacy. Gene. 2015; 589(2):142-50. DOI: 10.1016/j.gene.2015.10.010. View

10.

Chen L, Shu Y, Liang X, Chen E, Yee S, Zur A . OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. Proc Natl Acad Sci U S A. 2014; 111(27):9983-8. PMC: 4103324. DOI: 10.1073/pnas.1314939111. View

11.

Tatsumi T, Takayama K, Ishii S, Yamamoto A, Hara T, Minami N . Forced lipophagy reveals that lipid droplets are required for early embryonic development in mouse. Development. 2018; 145(4). DOI: 10.1242/dev.161893. View

12.

Watanabe T, Endo A . Teratogenic effects of maternal biotin deficiency on mouse embryos examined at midgestation. Teratology. 1990; 42(3):295-300. DOI: 10.1002/tera.1420420313. View

13.

Luzzo K, Wang Q, Purcell S, Chi M, Jimenez P, Grindler N . High fat diet induced developmental defects in the mouse: oocyte meiotic aneuploidy and fetal growth retardation/brain defects. PLoS One. 2012; 7(11):e49217. PMC: 3495769. DOI: 10.1371/journal.pone.0049217. View

14.

Atamna H, Newberry J, Erlitzki R, Schultz C, Ames B . Biotin deficiency inhibits heme synthesis and impairs mitochondria in human lung fibroblasts. J Nutr. 2006; 137(1):25-30. DOI: 10.1093/jn/137.1.25. View

15.

Sanchez-Lazo L, Brisard D, Elis S, Maillard V, Uzbekov R, Labas V . Fatty acid synthesis and oxidation in cumulus cells support oocyte maturation in bovine. Mol Endocrinol. 2014; 28(9):1502-21. PMC: 5414796. DOI: 10.1210/me.2014-1049. View

16.

Baez-Saldana A, Gutierrez-Ospina G, Chimal-Monroy J, Fernandez-Mejia C, Saavedra R . Biotin deficiency in mice is associated with decreased serum availability of insulin-like growth factor-I. Eur J Nutr. 2009; 48(3):137-44. DOI: 10.1007/s00394-009-0773-8. View

17.

Zhang X, Wu X, Lu S, Guo Y, Ma X . Deficit of mitochondria-derived ATP during oxidative stress impairs mouse MII oocyte spindles. Cell Res. 2006; 16(10):841-50. DOI: 10.1038/sj.cr.7310095. View

18.

Fujimoto W, Inaoki M, Fukui T, Inoue Y, Kuhara T . Biotin deficiency in an infant fed with amino acid formula. J Dermatol. 2005; 32(4):256-61. DOI: 10.1111/j.1346-8138.2005.tb00758.x. View

19.

Li Y, Na K, Lee H, Lee E, Paik Y . Contribution of sams-1 and pmt-1 to lipid homoeostasis in adult Caenorhabditis elegans. J Biochem. 2011; 149(5):529-38. DOI: 10.1093/jb/mvr025. View

20.

Watanabe T . Dietary biotin deficiency affects reproductive function and prenatal development in hamsters. J Nutr. 1993; 123(12):2101-8. DOI: 10.1093/jn/123.12.2101. View