Effects of coenzyme q10 supplementation on metabolic and reproductive outcomes in obese rats

Abstract

Obesity, a global epidemic, is linked to adverse reproductive outcomes, including infertility and ovulation dysfunction. The cafeteria diet (CAF) serves as an animal model mirroring Western diet habit. Coenzyme Q10 (CoQ10), known for enhancing reproductive outcomes in various pathologies, is not fully understood for its effects on obesity treatment. Here, obesity was modeled using CAF-fed rats to assess CoQ10's impact on metabolic and ovarian disruptions caused by obesity. Wistar rats were divided into control (standard diet) and obese (CAF diet) groups. After 75 days, half of each group received oral CoQ10 (5 mg/kg) for 13 days, while the rest received a vehicle. Animals were euthanized during the estrus phase, and blood and ovaries were collected for analysis. CAF caused increased body weight gain (p < 0.01) associated with hyperglycemia, hypertriglyceridemia, and hypercholesterolemia (p < 0.05). Moreover, it caused a reduction in the number of AMH + follicles (p < 0.001), increasing follicular atresia (p < 0.05) and serum estradiol levels (p < 0.05). Obesity also altered the estrous cycle and reduced the ovulation rate (p < 0.05). CoQ10 administration showed beneficial effects on all ovarian disruptions but had no effect on the metabolic alterations induced by obesity. In summary, CoQ10 could be an additional treatment for obesity-related infertility in patients with normal metabolic profiles. While CoQ10 does not affect metabolic parameters influenced by obesity, crucial for reproductive issues and offspring health, it is recommended as part of a treatment plan that includes a balanced diet and increased physical activity for obese individuals with metabolic alterations seeking pregnancy.

Keywords: Coenzyme Q10; Metabolism; Obesity; Ovulation.

Fig. 1

Body weight gain of rats fed with standard chow (Control, open circles) and CAF diet (Obese, grey triangles) during diet-protocol. After that, half the animals of each group were administered orally with CoQ10 while the other half received vehicle, resulting in 4 groups: Control, ControlQ10, Obese and ObeseQ10 (insert). Each time point represents the mean ± S.D. (n = 10). Two-way ANOVA (repeated measurements) followed by Bonferroni comparisons test: * p < 0.05 between groups

Fig. 2

Blood glucose levels during the glucose tolerance test in control and obese rats that were treated (controlQ10: open squares, and obeseQ10: filled triangles), or not (control: open circles, obese: grey triangles), with Coenzyme Q10. Each time point represents the mean ± S.D. (n = 5). Two-way ANOVA (repeated measurements) followed by Bonferroni comparisons test. No significant differences between groups were detected

Fig. 3

Blood glucose levels during the insulin tolerance test in control and obese rats that were treated (controlQ10: open squares, and obeseQ10: filled triangles), or not (control: open circles, obese: grey triangles), with Coenzyme Q10. Each time point represents the mean ± S.D. (n = 5). Two-way ANOVA (repeated measurements) followed by Bonferroni comparisons test. No significant differences between groups were detected

Fig. 4

Estrous cycle evaluation in control and obese rats that were treated, or not, with Coenzyme Q10. Percentage of time spent in each stage (A: proestrus, B: metestrus, C: estrus and D: diestrus). Data is expressed as mean ± S.D. (n = 10). Two-way ANOVA followed by Bonferroni comparisons test. Groups sharing the same letter (a, b, c) are not significantly different from each other. a vs. b p < 0.05 in C and p < 0.005 in D

Fig. 5

Serum progesterone (A), estrone (B) and estradiol (C) levels in control and obese rats that were treated, or not, with Coenzyme Q10. Data is expressed as mean ± S.D. (n = 5). Two-way ANOVA followed by Bonferroni comparisons test. Groups sharing the same letter (a, b, c) are not significantly different from each other. a vs. b p < 0.05

Fig. 6

Quantification of viable follicles in control and obese rats that were treated, or not, with Coenzyme Q10: primordial (A), primary (B), secondary (C), antral (D), preovulatory (E) follicles and corpora lutea (F). Data is expressed as mean ± S.D. (n = 5). Two-way ANOVA followed by Bonferroni comparisons test. Groups sharing the same letter (a, b, c) are not significantly different from each other. a vs. b p < 0.01 in B and p < 0.05 in C, D and F

Fig. 7

Quantification of atretic follicles in control and obese rats that were treated, or not, with Coenzyme Q10: antral (A) and preovulatory (B) follicles. Data is expressed as mean ± S.D. (n = 5). Two-way ANOVA followed by Bonferroni comparisons test. Groups sharing the same letter (a, b, c) are not significantly different from each other. a vs. b p < 0.05

Fig. 8

Ovarian mRNA levels of StAR (A), Aromatase (B) and Hsd17b1 (C) in control and obese rats that were treated, or not, with Coenzyme Q10. Data is expressed as mean ± S.D. (n = 5). Two-way ANOVA followed by Bonferroni comparisons test. No significant differences between groups were detected

Fig. 9

Anti-Müllerian hormone (AMH) immunohistochemical staining in ovaries. Left panel: Representative sections showing AMH immunoreactivity (AMH+) in granulosa cells of primary, secondary, and antral follicles from Control (A), ControlQ10 (B), Obese (C) and ObeseQ10 (D) rats. Arrowheads shows AMH- follicles. (E) Antral follicle showing AMH staining in granulosa (G) but not in theca cells (T); O: oocyte. (F) Negative control. Scale bars: A-D and F = 500 µm; E = 20 µm. Right panel: Number of AMH+ primary (A), secondary (B) and antral (C) follicles relative to the total number of follicles in each stage. Data is expressed as mean ± S.D. (n = 5). Two-way ANOVA followed by Bonferroni comparisons test. Groups sharing the same letter (a, b, c) are not significantly different from each other. a vs. b p <0.001