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Ovarian failure in diabetic rat model: nuclear factor-kappaB, oxidative stress, and pentraxin-3
Oytun Erbas1, Halil Gursoy Pala2, Emel Ebru Pala3
1Physiology Department, School of Medicine, Gaziosmanpasa University, Tokat, Turkey.
Objective:
The aim of the present study was to investigate the effects of diabetes mellitus (DM) on ovarian reserve and injury by considering laboratory and histopathological parameters in rat models.
Materials And Methods:
An experimental DM model was created in 16 rats. Eight rats with normal blood glucose levels were included in the control group. Diabetic rats were divided randomly into two groups: nontreated and resveratrol-treated groups. Histopathological examination and nuclear factor (NF)-κB immunoexpression level determination were performed. Plasma malondialdehyde, glutathione, pentraxin-3, and anti-Müllerian hormone levels were measured. Relations between the variables were compared by Student t test, analysis of variance, and Mann-Whitney U and χ(2) tests.
Results:
We found statistically significantly lower glutathione and anti-Müllerian hormone levels, and higher malondialdehyde and pentraxin-3 levels in nontreated diabetic group when compared with the control and resveratrol-treated diabetic groups. Stromal degeneration, follicle degeneration, stromal fibrosis scores, and NF-κB immunoexpression levels were significantly higher in nontreated diabetic rats. Primordial and primary follicle counts were significantly lower in the nontreated diabetic group when compared with the control and resveratrol-treated groups. There was no statistically significant difference in secondary and tertiary follicles between these groups.
Conclusion:
These findings provide strong evidence that the ovarian follicle pool in nontreated diabetic rats is affected in the early stages of the follicle development process. We precluded negative effects of DM on ovaries by inhibiting the NF-κB pathway with resveratrol. We thought that the NF-κB pathway plays a role in the pathophysiology of ovarian failure in diabetic rats. Further studies should evaluate this precise mechanism that leads to a decline in the anti-Müllerian hormone levels. In addition, the relationship between this abnormality and reproductive function in diabetic patients should be analyzed further.
Insights
Diabetes mellitus (DM) significantly impacts ovarian reserve, reducing anti-Müllerian hormone and damaging follicles. Resveratrol treatment mitigated these effects by inhibiting the NF-κB pathway, suggesting its role in diabetic ovarian injury.
Area of Science:
- Endocrinology and Reproductive Biology
- Pathology
- Pharmacology
Background:
- Diabetes mellitus (DM) is a systemic disease with potential adverse effects on reproductive health.
- Ovarian reserve and function can be compromised in diabetic individuals, but the underlying mechanisms require further elucidation.
- Oxidative stress and inflammation are implicated in the pathophysiology of DM complications.
Purpose of the Study:
- To investigate the impact of diabetes mellitus on ovarian reserve and injury in a rat model.
- To evaluate the protective effects of resveratrol on ovarian parameters in diabetic rats.
- To explore the role of the nuclear factor-kappa B (NF-κB) pathway in diabetic ovarian dysfunction.
Main Methods:
- An experimental diabetes mellitus model was established in rats.
- Diabetic rats were treated with resveratrol, and compared to untreated diabetic and control groups.
- Ovarian reserve was assessed through histopathological examination, follicle counts, and measurement of plasma anti-Müllerian hormone, malondialdehyde, glutathione, pentraxin-3, and NF-κB immunoexpression.
Main Results:
- Diabetic rats exhibited significantly lower glutathione and anti-Müllerian hormone levels, and higher malondialdehyde and pentraxin-3 levels compared to controls.
- Histopathological analysis revealed increased stromal degeneration, follicle degeneration, stromal fibrosis, and elevated NF-κB immunoexpression in untreated diabetic rats.
- Primordial and primary follicle counts were significantly reduced in diabetic rats, an effect ameliorated by resveratrol treatment.
Conclusions:
- Diabetes mellitus negatively affects ovarian reserve, particularly impacting early follicle development.
- Resveratrol demonstrates a protective effect against DM-induced ovarian injury, likely through the inhibition of the NF-κB pathway.
- The NF-κB pathway is implicated in the pathophysiology of ovarian failure in diabetic rats, warranting further investigation into its precise mechanisms and clinical relevance.
