The Study Of The Relationship Between The Advanced Glycation End Products And Their Receptors And Ovarian Response In The Controlled Ovulation Stimulation Cycles

BackgroundAfter 30 years of development, IVF-ET (in vitro fertilization and embryo transfer), the main technology of ART (assisted reproductive technology) for the human being, has been becoming more mature. As the primary step of the IVF-ET, COH (controlled ovarian stimulation) is very important. However, there are still 9%-24% of POR (Poor Ovary Respond) occurrence which will induce the higher cycle cancellation rate and low pregnancy because of poor quantity and quality oocytes and embryos. The nature of the POR occurrence is the decline of ovarian reserve. Ovarian reserve function means the growth, development and mature oocyte formation abilities of the follicles stored in Ovarian, which reflects the reproductive potential of women. But the specific aetiology for the POR occurrence is unknown。AGEs (advanced glycation end products) are the non-enzymatic glycosylation reaction products of the protein amino and the sugar aldehyde group, which present in normal human bodies and are closely related to aging. Accumulation of AGEs will caused the body damage by directly or indirectly ways. Recently, AGEs were considered as the molecular basis of age-related ovarian damage, which may be involved in the starting of ovarian aging. At present The research about AGEs in ART-patients is poor and controversy. The receptor for advanced glycation end products(RAGE)might be pivotal and related ovarian damage, however, How The up-regulation of the RAGE affects ovarian function was unknown. Thus, we examined the levels of AGEs in serum、follicular fluid and the expression of RAGE mRNA on granulosa cells in woman in the controlled ovulation stimulation cycles.ObjectiveThe purpose of our study is to determine the AGEs levels in serum and follicular fluid, and RAGE mRNA expression on granulosa cells of different ovary respond groups during COH cycle, and to investigate their relationships with POR and ART outcome.MethodsSeventy-three patients during COH cycle were selected and devided into three groups according to their different ovary responds:26 cases of POR,26 cases of MOR(Moderate Ovary Respond) and 21 cases of HOR(High Ovary Respond). The AGEs levels in serum and follicular fluid was determined by ELISA (enzyme-linked immunosorbent assay) and RAGE mRNA expression on granulosa cellswas detected by Real-time PCR, and the correlation between the AGEs and there receptor with ART outcome were analyzed respectively.Results1. Gn-AGEs levels of three groups are 3.62(4.48)μg/ml(POR),1.44(2.80) ug/ml (MOR) and 2.91 (4.48) ug/ml (HOR), respectively. No significant differences are existed between groups (p>0.05).2. S-AGEs levels of three groups are 2.57 (2.33) ug/ml(POR),1.56 (1.72) ug/ml (MOR) and 2.60 (2.54) ug/ml (HOR), respectively. No significant differences are existed between groups (p>0.05).3. FF-AGEs levels of three groups are 4.49(3.89)ug/ml(POR),2.46(3.72) ug/ml (MOR) and 3.53 (4.63) ug/ml (HOR), respectively. The significant differences are existed between the poor response group and the other groups(p< 0.05).4. The RAGE mRNA expression on granulosa cells of three groups are 1.35 (3.41) (POR),0.65 (1.15) (MOR) and 0.45 (0.87) (HOR), respectively. The significant differences are existed between the poor response group and the other groups(p< 0.05).5. FF-AGEs showed significant negative correlations with retrieved oocytes, r=-0.239, p=0.042; The RAGE mRNA expression showed significant negative correlations with retrieved oocytes too, r=-0.380, p=0.001.6. The Gn-AGEs levels of pregnancy group and non-pregnancy group are 3.31 (3.34) (ug/ml) vs 2.80 (4.34) (ug/ml)respectively. No significant differences are existed between them. The S-AGEs levels of pregnancy group and non-pregnancy group are 1.56 (1.86) (ug/ml) vs 2.53 (1.37) (ug/ml) respectively. No significant differences are existed between them; The FF-AGEs levels of those two groups above are 3.82 (3.11) (ug/ml) vs 4.52 (3.45) (ug/ml) respectively. No significant differences are existed between them. The RAGE mRNA expression on granulosa cells of those two groups are 0.71 (0.83) vs 1.41 (2.92), also showed no significant differences.Conclusion1. The elevation of the follicular fluid AGEs may be one of a key factor of poor ovarian response.2.The up-regulation of RAGEmRNA on granulosa cells might be pivotal and related ovarian damage.