کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5561662 | 1562152 | 2017 | 14 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Phosphoramide mustard induces autophagy markers and mTOR inhibition prevents follicle loss due to phosphoramide mustard exposure Phosphoramide mustard induces autophagy markers and mTOR inhibition prevents follicle loss due to phosphoramide mustard exposure](/preview/png/5561662.png)
- Phosphoramide mustard histologically alters follicle structure prior to demise.
- Rapamycin prevents phosphoramide mustard-induced follicle loss.
- Phosphoramide mustard tended to reduce ovarian ABCB1 protein.
Phosphoramide mustard (PM) is an ovotoxic metabolite of cyclophosphamide. Postnatal day 4 Fisher 344 rat ovaries were exposed to vehicle control (1% DMSO) or PM (60 μM) ± LY294002 or rapamycin for 2 or 4 d. Transmission election microscopy revealed abnormally large golgi apparatus and electron dense mitochondria in PM-exposed ovaries prior to and at the time of follicle depletion. PM exposure increased (P < 0.05) mRNA abundance of Bbc3, Cdkn1a, Ctfr, Edn1, Gstp1, Nqo1, Tlr4, Tnfrsfla, Txnrd1 and decreased (P < 0.05) Casp1 and Il1b after 4d. PM exposure increased (P < 0.1) BECN1 and LAMP, decreased (P < 0.1) ABCB1 and did not alter ABCC1 protein. LY294002 did not impact PM-induced ovotoxicity, but decreased ABCC1 and ABCB1 protein. Rapamycin prevented PM-induced follicle loss. These data suggest that the mammalian target of rapamycin, mTOR, may be a gatekeeper of PM-induced follicle loss.
Journal: Reproductive Toxicology - Volume 67, January 2017, Pages 65-78