The effect of adipose-derived mesenchymal stem cell treatment on mTOR and p-mTOR expression in ovarian damage due to cyclophosphomide

Reprod Toxicol. 2021 Aug:103:71-78. doi: 10.1016/j.reprotox.2021.06.003. Epub 2021 Jun 10.

Abstract

Our aim is to investigate the effect of the Mesenchymal stem cell (MSC) administration on the release of Mammalian Target of Rapamycin (mTOR) and Phosphorylated- mTOR(p-mTOR) in Cyclophosphomide (CTX) induced ovarian damage. Rats divided into three groups. The first group was categorized as the control(C group;n = 6), the second group as CTX-administered group (CTX group;n = 6), and the third group as CTX and MSC-administered group (CTX + SC group;n = 6). CTX was injected intraperitoneally at 50 mg/kg on the first day and at 8 mg/kg during the following 13 days. In Group 3, adipose-derived MSCs (5 × 104) were injected locally into the ovary. Both ovaries were removed at the end of the 8th week. The follicle count was made. The expression of mTOR and p-mTOR was analyzed immunohistochemically. The follicles in the ovary of Group C were observed in normal structures. Degeneration was evident in the CTX group. In the CTX + SC group, the degenerative appearance monitored in the CTX group vanished in most areas, and fibrosis was greatly reduced. The number of follicles in the CTX group was lower than that of both C and CTX + SC groups (p < 005). In the C group, mTOR showed strong positive staining while mTOR and p-mTOR expression was negative in all follicles in the CTX group. Both mTOR and p-mTOR revealed moderate positive expression in the CTX + SC group. MSC therapy rescued the damage ovarian function created by CTX, reducing follicle loss. MSCs were shown to inhibit the loss of mTOR and p-mTOR signaling, which is key to meiosis in oocytes.

Keywords: Cyclophosphomide; Mesenchymal stem cell; Ovary; mTOR; p-mTOR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclophosphamide / toxicity*
  • Female
  • Mesenchymal Stem Cells*
  • Mutagens / toxicity*
  • Ovarian Follicle / drug effects
  • Ovary
  • Primary Ovarian Insufficiency
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Mutagens
  • Cyclophosphamide
  • mTOR protein, rat
  • TOR Serine-Threonine Kinases