Journal
FERTILITY AND STERILITY
Volume 96, Issue 5, Pages 1154-U122Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.fertnstert.2011.08.040
Keywords
Atresia; empty follicle syndrome; fertility; follicle; oocyte; ovary; mTOR kinase
Categories
Funding
- United Kingdom Medical Research Council [G0901839]
- Yale Department of Obstetrics, Gynecology, and Reproductive Sciences
- Donaghue Yale Women's Health Research Program
- MRC [G0901839, G1100357, G1002033] Funding Source: UKRI
- Medical Research Council [G0901839, G1002033, G1100357] Funding Source: researchfish
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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. (C) 2011 by American Society for Reproductive Medicine.)
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