RESUMEN
Autophagy, a process of controlled cellular self-digestion, could be involved in cyclic remodeling of the human endometrium. We investigated endometrial mRNA expression of 23 autophagy-related (ATG) genes and transcription factors in healthy controls (n = 12) and anovulatory polycystic ovary syndrome (PCOS) patients (n = 24), as well as in their subgroup (n = 12) before and after metformin treatment. The mRNA levels of transcription factor forkhead box protein O1 (FOXO1) and several molecules involved in autophagosome formation (ATG13, RB1-inducible coiled-coil 1), autophagosome nucleation (ATG14, beclin 1, SH3-domain GRB2-like endophilin B1), autophagosome elongation (ATG3, ATG5, γ-aminobutyric acid receptor-associated protein - GABARAP), and delivery of ubiquitinated proteins to autophagosomes (sequestosome 1), were significantly reduced in anovulatory PCOS compared to healthy endometrium. Free androgen index, but not free estrogen index, insulin levels, or body mass index, negatively correlated with the endometrial expression of ATG3, ATG14, and GABARAP in PCOS patients. Treatment of PCOS patients with metformin (2 g/day for 3 months) significantly increased the endometrial mRNA levels of FOXO1, ATG3, and UV radiation resistance-associated gene. These data suggest that increased androgen availability in PCOS is associated with metformin-sensitive transcriptional downregulation of endometrial autophagy.
Asunto(s)
Autofagia/genética , Regulación hacia Abajo/genética , Endometrio/metabolismo , Síndrome del Ovario Poliquístico/genética , Adulto , Autofagia/efectos de los fármacos , Estudios de Casos y Controles , Regulación hacia Abajo/efectos de los fármacos , Endometrio/efectos de los fármacos , Endometrio/patología , Femenino , Perfilación de la Expresión Génica , Humanos , Metformina/farmacología , Metformina/uso terapéutico , Síndrome del Ovario Poliquístico/tratamiento farmacológicoRESUMEN
BACKGROUND/AIM: Diabetes mellitus is associated with an increased risk for neonatal morbidity and mortality. One of the most important goals in treating pregnancies complicated with diabetes is keeping glucose level within the normal range, especially in the first trimester. A portable insulin pump for continuous subcutaneous insulin infusion (CSII) represents the best form of therapy for patients with type 1 diabetes mellitus during pregnancy. The aim of our study was to evaluate the effects of therapy with a portable insulin pump for continuous subcutaneous insulin infusion during the first trimester of pregnancy on the quality of glycoregulation and pregnancy outcome in women with type 1 diabetes mellitus. METHODS: A total of 17 newly diagnosed pregnant women with type 1 diabetes mellitus were treated with CSII therapy for three months. The parameters of glycoregulation (hemoglobin A, glycosylated--HbAlc, mean blood glucose value in daily profiles--MBG, daily requirement for insulin--IJ/kg BM), lipid levels, blood preassure and renal function were estimated before and after the therapy. These parameters were correlated with parameters of pregnancy outcome: fetal weight, APGAR score, duration of pregnancy. RESULTS: There was a significant improvement in HbA1c (8.94 +/- 1.62 vs. 6.90 +/- 1.22 %,p < 0.05), MBG (9.23 +/- 2.22 vs. 6.41 +/- 1.72 mmol/l, p < 0.01), and daily requirement for insulin (0.66 +/- 0.22 vs. 0.55 +/- 0.13 IJ/kg BM, p < 0.05) during the CSII therapy. There were significant correlations between fetal weight and HbAlc (r = -0.60, p < 0.05), triglyceride levels (r = -0.63, p < 0.01), and the number of pregnancies (r = -0.62, p < 0.01), as well as between APGAR score and MBG (r = -0.52, p < 0.05) and cholesterol levels (r = -0.65, p < 0,01) before a portable insulin pump was applicated. CONCLUSIONS: There was a significant improvement in the quality of glycoregulation during CSII therapy in the pregnant women with type 1 diabetes mellitus. The quality of glycoregulation in the moment of conception was the important factor for pregnancy outcome.