Relationship of Golgi phosphoprotein-3 expression with granulosa cells apoptosis and controlled ovarian hyperstimulation outcomes patients with polycystic ovary syndrome

Abstract

Objective To explore the effect of Golgi phosphoprotein-3 (GOLPH3) in granulosa cells of patients with polycystic ovary syndrome (PCOS) during controlled ovarian hyperstimulation (COH) cycles on granulosa cells apoptosis and COH outcomes. Methods Seventy eligible in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cases with PCOS owing to the tubal or male factors and 70 corresponding IVF/ICSI-ET cases with non-PCOS were included. Immunocytochemistry and Real-time PCR were used to detect the protein and mRNA expression of GOLPH3, Bcl-2, Bax and Caspase-3 in granulosa cells of the two groups, respectively. Meanwhile, the correlations of GOLPH3 expression with cells apoptosis factors (Bcl-2, Bax and Caspase-3) and COH outcomes were analyzed. Results 1) GOLPH3 protein was detected in the cytoplasm of granulosa cells in two groups. The expressions of GOLPH3 and Bcl-2 protein in PCOS group were lower than those in control group (P<0.05), while the expressions of Bax and Caspase-3 protein were higher than those in control group (P<0.05). 2) GOLPH3 mRNA and Bcl-2 mRNA in PCOS group were lower than those in control group (P<0.05). However, Bax mRNA and Caspase-3 mRNA were higher than those in control group (P<0.05). 3) Both the protein and mRNA levels of GOLPH3 expression in pregnant PCOS group were higher than those in non-pregnant PCOS group (P<0.05). 4) The expression of GOLPH3 protein in granulosa cells was strongly positively correlated with inhibit apoptosis factor Bcl-2 protein (P<0.001), and negatively correlated with pro-apoptosis factors Bax and Caspase-3 protein (P<0.001), meanwhile, presented positive correlation with COH outcomes, including the number of retrieved oocytes, two pronucleus (2PN) fertilizations, cleavages, high-quality embryos, high-quality blastocysts and available embryos. GOLPH3 mRNA was positively correlated with the number of high-quality embryos. Multivariate linear analysis discovered that GOLPH3 expression levels were positively associated with Bcl-2 level and the number of available embryos, while were negatively associated with Bax level. Conclusion Down-expression of GOLPH3 in granulosa cells of PCOS patients during COH period may be associated with the quality of oocytes and the unfavorable embryo developmental potential via promoting granulosa apoptosis. Key words: Golgi phosphoprotein-3 (GOLPH3); Polycystic ovary syndrome (PCOS); Granulosa cells (GC); Apoptosis