Glucotransporters (GLUTs) expression and function in human endometrium from normal and Polycystic Ovary Syndrome women (PCOS): Effect of long term metformin (M) treatment

PUSTOVRH C; VILLARROEL C; ARRIAGADA C; MUÑOZ A; KOHEN P; NESTLER J; DEVOTO L

Congreso; European Society of Human Reproduction and Embryology (ESHRE).; 2012

Glucotransporters (GLUTs) expression and function in the human endometrium from normal and polycystic ovary syndrome women (PCOS): Effect of long term treatment with metformin (M) 1, 2Pustovrh MC, 2Villarroel C, 2Arriagada C, 2Muñoz A, 2Kohen P, 2Nestler JE, 2Devoto L 1Laboratory of Developmental Biology. Department of Biodiversity and Experimental Biology. Institute of Physiology, Molecular Biology and Neurosciences. (IFIBYNE-CONICET-UBA). School of Exact and Natural Sciences. University of Buenos Aires, Argentina. Background: PCOS has a deleterious impact on fertility due to ovulatory dysfunction and an increased rate of spontaneous abortion. This syndrome is associated with hyperinsulinemia and insulin resistance in approximately 40-50% of cases. It has been suggested that an adequate control of glucose metabolism is an important step for establishing a receptive endometrium suitable for implantation. GLUTs regulate the movement of glucose between the extracellular and intracellular compartments, maintaining a constant source of glucose available for metabolism. The aim of this study was to assess GLUTs expression and function in the endometrium PCOS women with or without insulin resistance (IR) and IR-PCOS treated with a long term treatment with metformin (M-PCOS).Design and intervention: We recruited 14 healthy fertile women (C) and 20 PCOS patients: 6 anovulatory PCOS women without IR (NIR-PCOS), 8 insulin resistant PCOS women (IR-PCOS) and 6 IR-PCOS patients who were treated with Metformin 1700mg/day for two years (M-PCOS). A clinical evaluation was performed. An early-morning blood sample was obtained for the measurement of total testosterone, SHBG, fasting insulin and blood glucose levels in early follicular phase in ovulatory women and at random in anovulatory women, as previously reported. Free androgen index and the quantitative insulin sensitivity check index, (QUICKI) were calculated. An endometrial sample was obtained from each subject. Endometrial samples from C were collected during the proliferative phase (days 10-15, n = 8) and secretory phase (days 16-22; n = 6).Endometrial samples from NIR-PCOS and MIR-PCOS women were collected at proliferative phase (days 10-15) and at random in anovulatory IR-PCOS .GLUTs expression was evaluated by qRT-PCR and immunohistochemestry. Glucose uptake was assessed in-vitro incorporation of 2-desoxy- [3H]-glucose (2-DG) in both basal condition and under insulin stimulation (100 ng/ml). Results: GLUT1 endometrial expression was higher and GLUT4 expression was lower in secretory phase when compared with proliferative phase in C (p