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

Marie McLaughlin, Pasquale Patrizio, Umit Kayisli, Janelle Luk, Travis C. Thomson, Richard A. Anderson, Evelyn E. Telfer, Joshua Johnson

Research output: Contribution to journalArticlepeer-review

Abstract

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.)

Original languageEnglish
Pages (from-to)1154-1159.e1
Number of pages7
JournalFertility and Sterility
Volume96
Issue number5
DOIs
Publication statusPublished - Nov 2011

Keywords

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

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