Ovarian stimulated cycles reduce protection of follicular fluid against free radicals

• Published in: Free radical biology & medicine Vol. 145; pp. 330 - 335
• Main Authors: Pérez-Ruiz, Irantzu, Meijide, Susana, Ferrando, Marcos, Larreategui, Zaloa, Ruiz-Larrea, María-Begoña, Ruiz-Sanz, José-Ignacio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-12-2019
• Subjects: Assisted reproduction; Follicular fluid; Ovulation induction; Oxidative stress; Oxidative stress; NO; DBI; BM; H2O2; hGM; Ovulation induction; Assisted reproduction; GnRH; COH; rFSH; HPLC; ORAC; SOD; ACL; Follicular fluid; GPx; PON; NC; TAA; ROS; IVF; PI; DHA; PUFAs; ABTS
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2019.10.004

Controlled ovarian hyperstimulation cycle with exogenous gonadotropins (COH) is associated with clinical complications. The aim of this work was to determine whether COH alters the physiological antioxidant status of follicular fluid in women with no reproductive dysfunction, compared to the natural cycle (NC). In this longitudinal study, forty-one women (oocyte donors) consecutively underwent NC and COH. Follicular fluid was collected at oocyte retrieval and different redox biomarkers were determined: total antioxidant activity (TAA), oxygen radical absorbance capacity (ORAC), nitric oxide, α- and γ-tocopherol, the fatty acid composition, activities of superoxide dismutase, catalase, total and Se-dependent glutathione peroxidases, and the antioxidant paraoxonase (PON) family. Results showed that TAA (1.70 ± 0.03 mM versus 1.86 ± 0.03 mM, p < 0.05), α-tocopherol (4.37 ± 0.26 μM versus 5.74 ± 0.30 μM, p < 0.05), PON1 paraoxonase (245 ± 24 nmol/min/ml versus 272 ± 27 nmol/min/ml, p < 0.05), PON1 arylesterase (87.2 ± 4.6 μmol/min/ml versus 99.3 ± 4.8 μmol/min/ml, p < 0.05), and PON3 simvastatinase (13.48 ± 0.52 nmol/min/ml versus 16.29 ± 0.72 nmol/min/ml, p < 0.001) were significantly lower in COH versus NC. Fatty acids from COH were more saturated, increasing palmitate and decreasing the n-6 and total polyunsaturated fatty acids (PUFAs). Docosahexaenoic acid also increased (p < 0.05). Results suggest that COH could lead to premature ovarian aging and provide new insights into the possible prevention of the adverse effects of ovarian hyperstimulation by directing therapeutic applications to the maintenance of the redox balance and fatty acid status, with special attention to paraoxonase proteins and docosahexaenoic acid.
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•COH decreases the antioxidant status of follicular fluid from fertile women.•Antioxidant paraoxonase (PON) activities are lower in COH compared with natural cycle.•The content of docosahexaenoic acid is increased in COH.•Results suggest that COH could lead to a premature ovarian aging.•PONs and docosahexaenoic acid are promising targets to improve ovarian stimulation in assisted reproduction.