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)
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.