RESUMEN
Endocytosis is essential for uptake of many substances into the cell, but how it links to nutritional signalling is poorly understood. Here, we show a new role for endocytosis in regulating the response to low phosphate in Schizosaccharomyces pombe. Loss of function of myosin I (Myo1), Sla2/End4 or Arp2, proteins involved in the early steps of endocytosis, led to increased proliferation in low-phosphate medium compared to controls. We show that once cells are deprived of phosphate they undergo a quiescence response that is dependent on the endocytic function of Myo1. Transcriptomic analysis revealed a wide perturbation of gene expression with induction of stress-regulated genes upon phosphate starvation in wild-type but not Δmyo1 cells. Thus, endocytosis plays a pivotal role in mediating the cellular response to nutrients, bridging the external environment and internal molecular functions of the cell.
Asunto(s)
Endocitosis/fisiología , Regulación Fúngica de la Expresión Génica/fisiología , Cadenas Pesadas de Miosina/metabolismo , Fosfatos/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/metabolismo , Transducción de Señal/fisiología , Proteína 2 Relacionada con la Actina/genética , Proteína 2 Relacionada con la Actina/metabolismo , Eliminación de Gen , Cadenas Pesadas de Miosina/genética , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/genética , TranscriptomaRESUMEN
BACKGROUND: The variability in indications and low rate of pregnancy compared to IVF have led many authors to dismiss IUI and offer IVF first-line instead. OBJECTIVES: To determine what are the predictive factors for clinical pregnancy (CP) and live birth (LB) in intrauterine insemination (IUI) cycles following controlled ovarian stimulation (COS). METHODS: Retrospective unicentric study, between January 2009 and December 2016. Patients aged 18 to <43 years who had an IUI following COS with gonadotropins. Statistical analysis was performed using Chi square and logistic regression. RESULTS: 4146 cycles (1312 couples) included. Mean age was 34.7 +/- 4years. LBR per couple was 39% for anovulatory infertility compared to (p < 0.05) unex-plained infertility (28.6%), mixed (23.4%), male factor (20.1%), unilateral tubal (14.2%), low ovarian reserve (13.2%), and endometriosis (stage I and II) (11.1%). Multivariate analysis showed the following factors were associated with CP: Cycle rank ≤3 (Odds ratio (OR) = 1.5, 95% CI: 1.2-1.9, p < 0.001), age <38 years (OR = 1.5, 95% CI: 1.2-2, p < 0.001), ≥2 preovulatory follicles (OR = 1.4, 95% CI: 1.1-1.8, p = 0.004), TMSC ≥ 5 millions (OR = 1.8, 95% CI: 1.3-2.4, p < 0.001). Endometriosis, low ovarian reserve, unilateral tubal and male factor had a negative impact on CPR (OR = 0.3, 95% CI: 0.1-0.5, p < 0.001; OR = 0.4, 95% CI: 0.3-0.7, p < 0.001; OR = 0.5 95% CI: 0.3-0.9, p = 0.01; OR = 0.6, 95% CI: 0.4-0.8, p = 0.002 respectively) compared to anovulatory infertility. CONCLUSION: We confirm that IUI can be an efficient treatment in selected indications. Young patients with anovulatory infertility seem to be the ideal candidates, with a 39% LBR per couple.