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. 2024 Aug 26;28(3):471-482.
doi: 10.5935/1518-0557.20240033.

Omega 3 fatty acids preserve testicular function by ameliorating BPF-induced dysthyroidism: role of p53/Bcl-2 signaling and proton pump activities

Affiliations

Omega 3 fatty acids preserve testicular function by ameliorating BPF-induced dysthyroidism: role of p53/Bcl-2 signaling and proton pump activities

Adeyemi Fatai Odetayo et al. JBRA Assist Reprod. .

Abstract

Objective: Bisphenol F (BPF) is an endocrinedisrupting chemical, but information about its effect on thyroid hormones has not been fully explored. Omega 3 fatty acids (O3FA), on the other hand, are antioxidant and antiapoptotic agents. Therefore, this study explored the role and associated molecular mechanism of O3FA in BPF-induced hypothyroidism-mediated testicular dysfunction in male Wistar rats.

Methods: Twenty (20) male Wistar rats were randomized into four groups (n=5/group), namely: the control group; the BPF treated group (30 mg/kg of BPF); and the intervention groups (30mg/kg BPF + 100mg/kg O3FA (BPF+O3FA-L) and 30mg/kg BPF + 300mg/kg of O3FA for 28 days).

Results: Low and high doses of O3FA ameliorated BPF-induced hypothyroidism-mediated reduction in sperm quality, testosterone, luteinizing hormone, follicle-stimulating hormone, catalase, superoxide dismutase, total antioxidant capacity, and nuclear factor erythroid 2-related factor 2 and increases in estrogen, malondialdehyde, c-reactive protein, interleukin 1 beta, caspase 3. Furthermore, O3FA prevented BPF-induced Na+/K+-ATPase and Ca2+-ATPase dysfunction, estrogen receptor beta overexpression, and tumor protein P53 (p53)/ b-cell lymphoma 2 (Bcl-2) imbalance.

Conclusions: This study showed that O3FA ameliorated BPF-induced dysthyroidism-mediated testicular dysfunction by preventing proton pump dysfunction and p53/BCl-2 imbalance.

Keywords: apoptosis; bisphenol F; hypothyroidism; omega 3 fatty acid; p53/BCl-2 signaling; proton pump.

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Conflict of interest statement

CONFLICT OF INTERESTS

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Effect of omega 3 fatty acids on (a) sperm count (b) motility (c) morphology in BPF-exposed rats. a. p<0 .05 versus control, b. p<0.05 versus BPF, c. p<0.05 versus BPF + O3FA-L using one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test for pairwise comparison. BPF: Bisphenol F, O3FA-L: omega-3 fatty acid low dose, O3FA-H: omega-3 fatty acid high dose.
Figure 2
Figure 2
Effect of omega 3 fatty acids on serum (a) thyroxine (b) triiodothyronine (c) thyroid stimulating hormone (TSH) (d) luteinizing hormone (LH) (e) follicle stimulating hormone (FSH) (f) testosterone (g) estradiol in BPF-exposed rats. a. p<0.05 versus control, b. p<0.05 versus BPF, c. p<0.05 versus BPF + O3FA-L using oneway analysis of variance (ANOVA) followed by Tukey’s post hoc test for pairwise comparison. BPF: Bisphenol F, O3FA-L: omega-3 fatty acid low dose, O3FA-H: omega-3 fatty acid high dose.
Figure 3
Figure 3
Effect of omega 3 fatty acids on testicular (a) malondialdehyde (MDA) (b) catalase (CAT) (c) superoxide dismutase (SOD) (d) total antioxidant capacity (TAC) (e) nuclear factor erythroid 2-related factor 2 (nrf2) in BPF-exposed rats. a. p<0.05 versus control, b. p<0.05 versus BPF, c. p<0.05 versus BPF + O3FA-L using oneway analysis of variance (ANOVA) followed by Tukey’s post hoc test for pairwise comparison. BPF: Bisphenol F, O3FA-L: omega-3 fatty acid low dose, O3FA-H: omega-3 fatty acid high dose.
Figure 4
Figure 4
Effect of omega 3 fatty acids on testicular (a) interleukin 1 beta (IL-1β) (b) c-reactive protein (CRP) in BPF-exposed rats. a. p<0.05 versus control, b. p<0.05 versus BPF, c. p<0.05 versus BPF + O3FA-L using one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test for pairwise comparison. BPF: Bisphenol F, O3FA-L: omega-3 fatty acid low dose, O3FA-H: omega-3 fatty acid high dose.
Figure 5
Figure 5
Effect of omega 3 fatty acids on testicular caspase 3 in BPF-exposed rats. a. p<0.05 versus control, b. p<0.05 versus BPF, c. p<0.05 versus BPF + O3FA-L using one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test for pairwise comparison. BPF: Bisphenol F, O3FA-L: omega-3 fatty acid low dose, O3FA-H: omega-3 fatty acid high dose.
Figure 6
Figure 6
Effect of omega 3 fatty acids on testicular (a) sodium-potassium ATPase (Na-K ATPase) (b) calcium ATPase (Ca-ATPase) in BPF-exposed rats. a. p<0.05 versus control, b. p<0.05 versus BPF, c. p<0.05 versus BPF + O3FA-L using one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test for pairwise comparison. BPF: Bisphenol F, O3FA-L: omega-3 fatty acid low dose, O3FA-H: omega-3 fatty acid high dose.
Figure 7
Figure 7
Effect of omega 3 fatty acids on testicular estrogen receptor beta (ER β) in BPF-exposed rats. a. p<0.05 versus control, b. p<0.05 versus BPF, c. p<0.05 versus BPF + O3FA-L using one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test for pairwise comparison. BPF: Bisphenol F, O3FA-L: omega-3 fatty acid low dose, O3FA-H: omega-3 fatty acid high dose.
Figure 8
Figure 8
Effect of omega 3 fatty acids on testicular tumor protein p53 (p53) in BPF-exposed rats. a. p<0.05 versus control, b. p<0.05 versus BPF, c. p<0.05 versus BPF + O3FA-L using one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test for pairwise comparison. BPF: Bisphenol F, O3FA-L: omega-3 fatty acid low dose, O3FA-H: omega-3 fatty acid high dose.
Figure 9
Figure 9
Effect of omega 3 fatty acids on testicular B-cell lymphoma 2 (BCl-2) in BPF-exposed rats. a. p<0.05 versus control, b. p<0.05 versus BPF, c. p<0.05 versus BPF + O3FA-L using one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test for pairwise comparison. BPF: Bisphenol F, O3FA-L: omega-3 fatty acid low dose, O3FA-H: omega-3 fatty acid high dose.

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