Mitochondrial function in modulation of human granulosa cell steroidogenesis and female fertility

Abstract

OBJECTIVE: To evaluate mitochondrial function in human granulosa cells from infertile patients and examine the relationship between mitochondrial dysfunction and infertile clinical background.DESIGN: In order to clarify the relationship between hormone levels, mitochondrial function, granulosa cells steroidogenesis, and embryo quality, the granulosa cells were obtained from the individuals undergoing IVF-ET program at Reproductive Medical Center, Taipei Veterans General Hospital. The granulose cells were classified into one of four groups, endometriosis, polycystic ovary syndrome (PCOS), other female factor infertility, and male factor infertility groups.MATERIALS AND METHODS: The concentration of estradiol (E2) and progesterone were analyzed by radioimmunoassay. Cell viability, mitochondrial mass, and mitochondrial membrane potential were detected by flow cyometry with propidium iodide, nonyl acridine orange, and N,N,N',N'-tetramethylethylenediamine, respectively. In addition, the oocyte numbers, oocyte quality, fertilization rate, and pregnancy rate were also detected.RESULTS: In our finding, the significantly lower E2 levels were found in the endometriosis group (61% of the control, p=0.001). The serum E2 level from the individuals of chocolate cyst patients declined to 47% of the control. The metaphase II stage of oocyte was decreased to 55% of the control (p=0.02). The cell viability decreased to 86% of the control (p=0.02). Reduced mitochondrial mass (72% of the control, p=0.04) reduced mitochondrial membrane potential (77% of the control), and a lower fertilization rate (90% of the control, p=0.02) was found in PCOS groups. All of these findings were also demonstrated in the endometriosis group, including declined viability (p=0.05), lower mitochondrial mass (p=0.02), decreased mitochondrial membrane potential (p=0.02), and reduced fertilization rate (p=0.02).CONCLUSIONS: Mitochondrial dysfunction of the human granulosa cells may contribute to the decline of steroidogenesis, fertilization rate, oocyte maturation rate, oocyte quality, and fertility capacity. OBJECTIVE: To evaluate mitochondrial function in human granulosa cells from infertile patients and examine the relationship between mitochondrial dysfunction and infertile clinical background. DESIGN: In order to clarify the relationship between hormone levels, mitochondrial function, granulosa cells steroidogenesis, and embryo quality, the granulosa cells were obtained from the individuals undergoing IVF-ET program at Reproductive Medical Center, Taipei Veterans General Hospital. The granulose cells were classified into one of four groups, endometriosis, polycystic ovary syndrome (PCOS), other female factor infertility, and male factor infertility groups. MATERIALS AND METHODS: The concentration of estradiol (E2) and progesterone were analyzed by radioimmunoassay. Cell viability, mitochondrial mass, and mitochondrial membrane potential were detected by flow cyometry with propidium iodide, nonyl acridine orange, and N,N,N',N'-tetramethylethylenediamine, respectively. In addition, the oocyte numbers, oocyte quality, fertilization rate, and pregnancy rate were also detected. RESULTS: In our finding, the significantly lower E2 levels were found in the endometriosis group (61% of the control, p=0.001). The serum E2 level from the individuals of chocolate cyst patients declined to 47% of the control. The metaphase II stage of oocyte was decreased to 55% of the control (p=0.02). The cell viability decreased to 86% of the control (p=0.02). Reduced mitochondrial mass (72% of the control, p=0.04) reduced mitochondrial membrane potential (77% of the control), and a lower fertilization rate (90% of the control, p=0.02) was found in PCOS groups. All of these findings were also demonstrated in the endometriosis group, including declined viability (p=0.05), lower mitochondrial mass (p=0.02), decreased mitochondrial membrane potential (p=0.02), and reduced fertilization rate (p=0.02). CONCLUSIONS: Mitochondrial dysfunction of the human granulosa cells may contribute to the decline of steroidogenesis, fertilization rate, oocyte maturation rate, oocyte quality, and fertility capacity.