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

Oleh:

McLaughlin, Marie ; Patrizio, Pasquale ; Kayisli, Umit ; Luk, Janelle

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Fertility and Sterility (keterangan: ada di ClinicalKey) vol. 96 no. 05 (Nov. 2011), page 1154-1159.
Topik: Atresia; empty follicle syndrome; fertility; follicle; oocyte; ovary; mTOR kinase

Ketersediaan

Perpustakaan FK Nomor Panggil: F02.K.2011.01 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

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.

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