Format

Send to

Choose Destination
See comment in PubMed Commons below
Fertil Steril. 2011 Nov;96(5):1154-9.e1. doi: 10.1016/j.fertnstert.2011.08.040.

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

Author information

1
Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom.

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.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center