Sirtuin Gene Expression and Antioxidant Enzyme Activity in Poor Responders Classified by POSEIDON Criteria: Associations with Ovarian Reserve and Oxidative Stress


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Ateş M., Erdem A., Erdem M., Demirdağ E., Yar A. S., Yılmaz C.

81st Scientific Congress of the American Society for Reproductive Medicine, ASRM 2025, San-Antonio, Kuzey Mariana Adaları, 25 - 29 Ekim 2025, cilt.6, ss.127, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Cilt numarası: 6
  • Basıldığı Şehir: San-Antonio
  • Basıldığı Ülke: Kuzey Mariana Adaları
  • Sayfa Sayıları: ss.127
  • Gazi Üniversitesi Adresli: Evet

Özet

OBJECTIVE: Sirtuins and antioxidant enzymes such as glutathione peroxidase

(GPx), catalase (Cat), and superoxide dismutase (SOD) play key roles

in regulating oxidative stress, mitochondrial function, and cellular homeostasis

1

. Disruptions in these pathways may negatively effect oocyte quality and

ovarian stimulation outcomes in assisted reproductive technologies. This

study aimed to evaluate the expression levels of SIRT1, SIRT2, SIRT3,

SIRT4, and SIRT6 mRNA in follicular fluid and enzymatic activity of

GPx, Cat, and SOD in both follicular fluid and serum of poor responder patients

defined by POSEIDON Criteria compared to age-matched controls

with normal ovarian response.

MATERIALS AND METHODS: This prospective study was conducted

between August and November 2024. Patients aged 18–50 undergoing

IVF/ICSI were grouped as POSEIDON Groups 1, 2, 3 4 and two age-matched

control groups (Groups 5 and 6: <35 and ≥35 years, respectively). Exclusion

criteria were patients with PCOS and endometrioma. On oocyte retrieval

day, follicular fluid and serum samples were collected and stored at –80 ◦ C.

Sirtuin mRNA expression was quantified by qPCR; enzymatic activity of

GPx, Cat, and SOD was measured by ELISA in follicular fluid and serum.

Statistical analyses were performed using SPSS 25.0 and differences in

cDNA expression levels were compared with REST 2009 software. P <

0.05 was considered significant.

RESULTS: SIRT1, SIRT2, SIRT3, and SIRT6 mRNA levels were significantly

lower in POSEIDON Group 4 compared to the Group 5. SIRT4

expression was significantly higher in Group 4(p<0.05). Group 4 had significantly

lower SIRT2 and SIRT3 and higher SIRT4 expression levels than

Group 6(p<0.05). Serum Cat and GPx activity levels were significantly

higher in G5 and G3 compared to G4(p<0.05). A positive correlation was

observed between enzyme activity in serum and follicular fluid(r=0,791,

p<0,001; r=708, p<0,001; r=0,607, p<0,001;respectively). Serum antioxidant

activity levels were significantly higher in patients aged <35 compared

to those ≥35.

CONCLUSIONS: Lower SIRT1, SIRT2, SIRT3, and SIRT6 expressions

and diminished GPx, Cat, and SOD activity were observed in patients

with diminished ovarian reserve, especially in POSEIDON Group 4. In

contrast, SIRT4 was significantly upregulated in poor responders. Our

findings support the importance of oxidative stress in age-related infertility

of poor responder patients, characterized by downregulation of

SIRT1, SIRT2, SIRT3, and SIRT6 and impaired antioxidant enzyme activity.

Notably, the significant upregulation of SIRT4 in poor responders may

reflect a compensatory or maladaptive response to increased oxidative

stress. These results underscore the critical role of sirtuin pathways in

ovarian aging and dysfunction, and support their potential as therapeutic

targets and predictive biomarkers in personalized reproductive medicine.

IMPACT STATEMENT: Sirtuin expression and antioxidant enzyme activity

may serve as potential biomarkers for poor ovarian response in patients

undergoing IVF/ICSI. These findings support further investigation into

fertility-preserving and antioxidant-based therapeutic strategies in women

with low ovarian reserve.