Study on the relationship between SlRTl and oxidative stress in aged patients undergoing in vitro fertilization and embryo transfer cycles

Advanced maternal age (>35 year) is associated with a decline in ovarian reserve, which leads to a decrease in female fertility [1]. The age-related ovarian aging is closely related with oxidative stress (OS), which may lead to oocyte aging and affect oocyte quantity and quality [2]. OS promotes ovarian ageing-related changes, such as oocyte maturation, fertilization failure and embryo fragmentation, eventually resulting in poor embryo [3]. Reduced ovarian response to controlled ovarian stimulation is also associated with increased OS in the follicular environment [4]. At present, the effect of OS on ovarian function in elderly patients mostly stays in the correlation between follicular microenvironment oxidation level and reproductive outcome, and there is a lack of relevant mechanism research.

Age-related ovary aging has been associated with expression of genes. Sirtuins (SIRTs) control ovarian functions and can be markers of the pathological state of ovary [5,6]. A large body of evidence has shown that SIRTs are involved in regulating female reproductive function [7]. Silent information regulator 1 (SIRT1), a member of the SIRTs family, is involved in the expression of antioxidant defense factors and enzymes and also plays a role in apoptosis and regulation ovarian function and female fertility [8,9]. The SIRT1 is expressed in the human ovarian tissues and luteinized granulosa cells [10]. The expression of SIRT1 in ovaries is decreased with aging in pig [11]. Otherwise, more recent results provide that the SIRT1 can increase ovarian reserve and prolong reproductive life in mice [12,13]. SIRT1 also have a role in oocyte maturation and clinical pregnancy in human [14]. Serum SIRT1 on HCG day was negatively correlated with the number of blastocysts [15].

Follicular fluid (FF) provides an environment that controls oocyte growth and maturation and has centered on the molecular study of the follicular microenvironment [16]. The FF antioxidant potential was correlated with the number of retrieved/mature oocytes [17]. Granulosa cells (GCs) are closely related to egg development. Considering the important roles of SIRT1, and OS in FF and GCs are still not fully understood in aged patients undergoing in vitro fertilization and embryo transfer (IVF-ET). This study aims to assess the SIRT1 and OS levels in FF and GCs and explore the relationship between SIRT1 and OS.

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