mTOR kinase inhibition results in oocyte loss characterized by empty follicles in human ovarian cortical strips cultured in vitro

作者：McLaughlin Marie; Patrizio Pasquale; Kayisli Umit; Luk Janelle; Thomson Travis C; Anderson Richard A; Telfer Evelyn E; Johnson Joshua^*

来源：Fertility and Sterility, 2011, 96(5): 1154-U122.

DOI：10.1016/j.fertnstert.2011.08.040

• Atresia
• empty follicle syndrome
• fertility
• follicle
• oocyte
• ovary
• mTOR kinase

Objective: To determine whether oocyte loss is induced by mTOR kinase inhibition in human cortical strips as seen in model organisms in vivo and in vitro.
Design: Ovarian cortex was collected at two centers and cut into small strips. Strips were cultured for 6 days with or without the mTOR inhibitor rapamycin (RAP; 100 nM). Strips were then embedded in paraffin, and serial sections were prepared.
Setting: Samples were collected in general obstetric (Edinburgh), gynecologic surgery (New Haven), and fertility preservation assisted reproductive technology (ART) (New Haven) practices.
Patient(s): Ovarian cortex collected from patients (15-34 years of age) during cesarean section (donated tissue) was removed for the purposes of fertility preservation or was prepared after oophorectomy.
Intervention(s): Tissue was used for research purposes only, with no subsequent patient intervention.
Main Outcome Measure(s): Follicles were counted and assessed in each serial section. Caspase activity was monitored to determine whether mTOR inhibition activated apoptosis.
Result(s): The RAP inclusion in cultures results in significantly fewer follicles compared with ethanol vehicle-treated controls. Furthermore, RAP treatment resulted in the induction of follicles that lacked an oocyte in any serial section (30/161 follicles vs. 1/347 ethanol vehicle-treated follicles). Caspase activity was not elevated by RAP treatment.
Conclusion(s): mTOR inhibition results in a conserved destruction of the oocyte by adjacent granulosa cells (GC) in the absence of increased caspase activity. This model of oocyte loss is not consistent with classic apoptosis/atresia. (Fertil Steril (R) 2011;96:1154-9.

• 出版日期2011-11