Serum α-Klotho levels and DNA damage in cumulus cells of infertile endometriosis patients: A cross-sectional study

Esra Büsra Durdu, Selma Yazar, Burçin Şeyda Çorba, Erbil Yağmur, Pınar Erol Horozal
In: Journal of Endometriosis and Pelvic Pain Disorders · 2025 · vol. 17(3) , pp. 135–143 · doi:10.1177/22840265251327942 · W4409046206
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This study found that infertile endometriosis patients had significantly lower serum alpha-Klotho levels and increased DNA damage in cumulus cells compared to fertile controls.

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Abstract

Background: Endometriosis is a leading cause of infertility, with its pathophysiology involving multiple mechanisms that impact the female reproductive system. This cross-sectional study aimed to investigate the role of alpha-Klotho, a protein known for its anti-aging, antioxidant, and anti-inflammatory properties, in protecting cumulus cells from DNA damage in infertile women with endometriosis undergoing in vitro fertilization (IVF) treatment. Methods: The study included 67 participants: 32 fertile women and 35 infertile women diagnosed with endometriosis. The control group consisted of fertile women without endometriosis, who undergoing IVF treatment for male factor infertility. Serum alpha-Klotho levels were measured using Enzyme-Linked Immunosorbent Assay (ELISA), while DNA damage in cumulus cells was assessed using the comet assay. Results: The majority of participants were aged between 26 and 33 years. Of the 35 infertile patients undergoing IVF, most were on their third IVF cycle. A statistically significant difference in serum alpha-Klotho levels was observed between fertile and infertile endometriosis patient groups, with a 99% confidence level ( p < 0.001). Patients with chemical exposure had higher Klotho levels, with a statistically significant difference between those with and without exposure, at a 90% confidence level. However, no statistically significant difference was found in the total comet score (TCS) between the two groups ( p = 0.104). DNA damage in cumulus cells was significantly elevated in the infertile endometriosis patients, as indicated by an increased percentage of DNA tail length. Univariate and multivariate logistic regression analyses revealed as significant association between reduced alpha-Klotho levels and infertile endometriosis patients. The cut-off value for Klotho protein was determined to be 267.55, with a sensitivity of 96.9%, specificity of 88.6%. Conclusions: This study suggests that decreased alpha-Klotho levels and increased DNA damage in cumulus cells may contribute to infertility in women with endometriosis. The findings highlight the potential protective role of alpha-Klotho against DNA damage, which offering insights into fertility preservation and therapeutic strategies for endometriosis patients. However, the study’s cross-sectional design and small samples size limit the ability to draw causal inferences. Further longitudinal studies are needed to confirm these findings and explore the potential role of alpha-Klotho in the pathophysiology of endometriosis-associated infertility.
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