Oxidative and histological variations of LDLR -/- female mice ovaries submitted to different diets
Keywords:Dyslipidemia; Knockout female mice; Ovarian lipoperoxidation; Ovarian protein oxidation.
Objective: to evaluate the oxidative and histological variations of female mice’s ovaries submitted to different diets. Methodology: Wild female mice (C57BL6) and LDLR-/- were used. They were divided into 4 groups (n=10): WTS: fed a standard diet; WTHL: fed a high fat diet; KOS: LDLR-/-, fed a standard diet; KOHL: LDLR-/-, received a high fat diet. After 60 days, blood was collected in order to verify of plasma glucose and insulin levels, the HOMAir was updated and serum lipid level were measured. After euthanasia, the ovaries were collected, weighed, freshly examined, one ovary was sent for histological preparation and the other was sent for preparation for oxidative stress assessment. Results: The ingestion of high-fat diet caused hypercholesterolemia, both the KOHL and WTHL groups, when compared to their respective control groups. In the KOHL group, severe hypercholesterolemia caused insulin resistance, verified by the increase in HOMAir. Dietary and genetic hypercholesterolemia associated with insulin resistance, verified in the KOHL, group increased lipoperoxidation and ovarian protein oxidation. No group had ovarian anatomical alterations or differences between the numbers of follicles and corpora lutea. Conclusion: the association between genetic and dietary dyslipidemia caused ovarian oxidative stress and insulin resistance in the ovaries, but didn’t cause morphological and histological changes to the ovaries of mice.
Abreu, J. M., et al. (2021). Dyslipidemia’s influence on the secretion ovarian’s steroids in female mice. Research, Society and Development. v. 10, n. 13.
Agarwal, A., Saleh, R. A., & Bedaiwy, M. A. (2003). Role of reactive oxygen species in the pathophysiology of human reproduction. Fertility and sterility. 79 (4), 829-843.
Benzie, I. F. F. (1996). Lipid peroxidation: A review of causes, consequences, measurement and dietary influences. Published online: 06 Jul 2009. 233-261. https://doi.org/10.3109/09637489609012586
Bradford, M. M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem, v. 72, p. 248-54. < https://www.ncbi.nlm.nih.gov/pubmed/942051 >.
Carvalho-Filho, M. A., et al. (2009). Aspirin attenuates insulin resistance en muscle of diet-induced obese rats by inhibiting inducible nitric oxide synthase production and S-nitrosylation of IRbeta/IRS-1 and Akt. Diabetologia. 52, 2425-34. https://link.springer.com/article/10.1007%2Fs00125-009-1498-1
Curtis, J. M., et al. (2012). Protein carbonylation and metabelaolic control systems. Trends Endocrinol Meta. 23, 399-406. Disponível em: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408802.
Evans, J. L., et al. (2002). Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev. 23:599 – 622.
Fair, T. (2003). Follicular oocyte growth and acquisition of developmental competence. Animal Reproduction Science. Amsterdam, NL. (78), 203-216.
Friedewald, W. T., Levy, R. I., & Fredrickson, D. S. (1972). Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical chemistry, 18(6), 499-502.
Garcia, J. A. D., et al. (2011). Efeito anti-inflamatório da lipoproteína de alta densidade no sistema cardiovascular de camundongos hiperlipidêmicos (Antiinflammatory effect of high density lipoprotein on the cardiovascular system of hyperlipidemic mice). Rev Port Cardiol. 30 (10), 763–769.
Giacomini, M. M., Hahn, S., & Siqueira, L. O. (2013). Análise de correlação do perfil lipídico e dano oxidativo em pacientes diabéticos. Revista de Ciências Farmacêuticas Básica e Aplicada. 34 (2).
Gratas-Delamarche A., et al. (2014). Physical inactivity, insulin resistance, and the oxidative-inflammatory. Free Radic Res. 48(1), 93-108.
Guyton, A. C. & Hall, J. E. (2002). Tratado de fisiologia médica. 10ed. Rio de Janeiro, Guanabara Koogan.
Hafez, E.S.E. & Hafez, B. (2004). Reprodução Animal. 7ed. Manole.
Hedrick, C. C., Castellani, L. W., Wong, H., & Lusis, A. J. (2001). In vivo interactions of apoA-II, apoA-I, and hepatic lipase contributing to HDL structure and antiatherogenic functions. Journal of lipid research. 42(4), 563-570.
Henriksen, E. J., et al. (1997). Stimulation by -lipoic acid of glucose transport activity in skeletal muscle of lean and obese Zucker rats. Life Sci. 61:805– 812.
Hopps, E. & Caimi, G. (2013). Protein oxidation in metabolic syndrome. Clinical and Investigative Medicine. E1-E8.
Jozwik, M., Wolczynski, S., Jozwik, M. & Szamatowicz, M. (1999). Oxidative stress markers in preovulatory follicular fluid in humans. Molecular human reproduction. 5(5), 409-413.
Junqueira, L. C. U & Carneiro, J. (1979). Histologia básica. 4ª ed. Guanabara Koogan.
Kheradmand, A., Alirezaei, M. & Birjandi, M. (2010). Ghrelin promotes antioxidant enzyme activity and reduces lipid peroxidation in the rat ovary. Regul Pept. Jun 8;162(1-3):84-9. doi: 10.1016/j.regpep.2010.02.008. Epub 2010 Feb 19. PMID: 20171996.
Koche, J. C. (2011). Fundamentos de metodologia científica. Petrópolis: Vozes.
Louhio, H., et al., (2000). The effects of insulin, and insulin-like growth factors I and II on human ovarian follicles in long-term culture. Molecular human reproduction. 6 (8), 694-698.
Martins, A. M., et al. (2020). Grape juice attenuates left ventricular hypertrophy in dyslipidemic mice. Plos one. v. 15, n. 9, p. e0238163.
Moore, K. L. & Persaud, T. V. N. (1994). Embriologia Clínica. 5ed. Guanabara Koogan. Rio de Janeiro.
Sabatini, L., et al. (1999). Superoxide dismutase activity in human follicular fluid after controlled ovarian hyperstimulation in women undergoing in vitro fertilization. Fertility and sterility, 72(6), 1027-1034.
Santos, I. S., et al. (2017). Insulin resistance is associated with carotid intima-media thickness in non-diabetic subjects. A cross-sectional analysis of the ELSA-Brasil cohort baseline. Atherosclerosis. v. 260, p. 34-40.
Sarto, D. A. Q. S., et al. (2018). Dry Extract of Passiflora incarnata L. leaves as a Cardiac and Hepatic Oxidative Stress Protector in LDLr-/- Mice Fed High-Fat Diet. 61.
Souza, C. T. (2018). Envolvimento da inflamação subclínica e do estresse oxidativo na resistência à insulina associada a obesidade. HU rev. 211-220.
Sugino, N., et al. (1996). Changes in activity of superoxide dismutase in the human endometrium throughout the menstrual cycle and in early pregnancy. Human Reproduction. 11(5), 1073-1078.
Tamate, K., Sengoku, K., & Ishikawa, M. (1995). The role of superoxide dismutase in the human ovary and fallopian tube. Journal of Obstetrics and Gynaecology. 21(4), 401-409.
Tian, J, et al. (2006). Hyperlipidemia is a major determinant of neointimal formation in LDL receptor-deficient mice. Biochemical and biophysical research communications. 345(3), 1004-1009.
Van Den Hurk, R. & Zhao, J. (2005). Formation of mammalian oocytes and their growth, differentiation and maturation within ovarian follicles. Theriogenology. (63), 1717–1751. https://www.ncbi.nlm.nih.gov/pubmed/15763114.
Winterbourn, C. C. (1981). Production of hydroxyl radicals from paraquat radicals and H2O2. FEBS Letters. 128 (2), 339-342 https://doi.org/10.1016/0014-5793(81) 80112-3.
How to Cite
Copyright (c) 2022 Juliana Maganha Abreu; Gérsika Bitencourt Santos; Juliana Marques Mencarelli; Ester Siqueira Caixeta; Jairo Pereira Neves; Cloves Gomes de Carvalho Filho ; Flávia Helena Pereira; Nelma de Mello Silva Oliveira; Giulia Martins Di-Santis; Jose Antonio Dias Garcia
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.