The Impact of Vitamin D on Follicular Development and Inflammatory Markers in Experimental Polycystic Ovary Syndrome

Year 2025, Volume: 11 Issue: 3, 160 - 178, 30.08.2025

Seçil Tan , Gülçin Abban Mete , Semih Tan , Nazlı Çil , Mücahit Seçme , Yavuz Dodurga , Ergun Mete

Abstract

Objective: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder among women of reproductive age, characterized by chronic anovulation, infertility, hyperandrogenism, and hirsutism. Additionally, PCOS is associated with metabolic disturbances such as insulin resistance, obesity, endothelial dysfunction, and metabolic syndrome. Recent research suggests that chronic inflammation and vitamin D deficiency may play a role in these comorbidities. However, studies investigating the relationship between vitamin D and PCOS have yielded conflicting results. Moreover, the immunohistochemical mechanisms by which inflammatory cytokines, including IL-1β, IL-6, and TNF-α, affect ovarian tissue in PCOS remain unclear.
Method: This study aimed to evaluate the short-term and mid-term effects of vitamin D on IL-1β, IL-6, and TNF-α expression in the ovaries of a dehydroepiandrosterone (DHEA)-induced PCOS rat model. Two different vitamin D administration strategies were investigated: pre-treatment (daily administration starting two hours before PCOS induction) and post-treatment (daily administration starting on day 20 of DHEA injection and continuing throughout the experimental period). The effects of vitamin D on ovarian inflammation and follicular morphology were analyzed.
Results: According to hematoxylin-eosin staining results, the number of cystic follicles was significantly increased in the PCOS group (Group 2: 7.17±0.87) compared to the control group (Group 1: 2.17±0.40, p=0.002), whereas early vitamin D treatment significantly reduced this number (Group 3: 4.00±0.51, p=0.009). However, in the long-term PCOS group (Group 4: 8.33±1.74), the number of cystic follicles was the highest among all groups, showing no significant difference compared to Group 2 (p=0.747). In the short term, vitamin D did not significantly alter IL-1β, IL-6, or TNF-α expression in ovarian tissue but effectively reduced the number of cystic follicles. However, in the prolonged exposure group, an increase in IL-1β, IL-6, and TNF-α expression was observed. Although RT-PCR analysis revealed increased expression levels of IL-
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1β, IL-6, and TNF-α genes in all groups compared to the control group, a statistically significant elevation was observed only in the long-term PCOS group for IL-6 (p=0.016) and IL-1β (p=0.036).
Conclusion: While vitamin D has demonstrated anti-inflammatory properties, it also plays a crucial role in follicular development, oocyte maturation, ovulation, and menstrual cycle regulation. The observed increase in inflammatory cytokines in vitamin D-treated groups might suggest a transient physiological response potentially associated with efforts to restore disrupted reproductive processes. In the short term, vitamin D significantly reduced cystic follicle formation but did not markedly impact ovarian inflammation markers. Long-term studies are required to determine the sustained effects of vitamin D at the molecular and tissue levels and to elucidate the precise stage at which it begins to mitigate the metabolic consequences of PCOS

Keywords

Vitamin D , Polycystic Ovary Syndrome (PCOS) , Folliculogenesis , Inflammatory Cytokines , Ovarian Morphology

Ethical Statement

Ethics committee approval was received for this study from Pamukkale University Animal Experiments Ethics Committee with the decision number PAUHDEK-2015/03.

Supporting Institution

Pamukkale University Scientific Research Projects Coordination Unit

Project Number

2015SBE005

Thanks

We would like to thank Pamukkale University Scientific Research Projects Coordination Unit for supporting our study with the project number 2015SBE005.

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