Ataxia Telangiectasia Mutated coordinates the ovarian DNA repair and atresia-initiating response to phosphoramide mustard.

Ataxia Telangiectasia Mutated coordinates the ovarian DNA repair and atresia-initiating response to phosphoramide mustard. Biol Reprod. 2019 Aug 22;: Authors: Clark KL, Keating AF Abstract Ataxia telangiectasia mutated (ATM) protein recognizes and repairs DNA double strand breaks (DSB) through activation of cell cycle checkpoints and DNA repair proteins. Atm gene mutations increase female reproductive cancer risk. Phosphoramide mustard (PM) induces ovarian DNA damage and destroys primordial follicles, and pharmacological ATM inhibition prevents PM-induced follicular depletion. Wild-type (WT) C57BL/6 or Atm+/- mice were dosed once intraperitoneally with sesame oil (95%) or PM (25 mg/kg) in the proestrus phase of the estrous cycle and ovaries harvested 3 days thereafter. Atm+/- mice spent ~ 25% more time in diestrus phase than WT. LC-MS/MS on ovarian protein was performed and bioinformatically analyzed. Relative to WT, Atm+/- mice had 64 and 243 proteins increased or decreased in abundance, respectively. In WT mice, PM increased 162 and decreased 20 proteins. In Atm+/- mice, 173 and 37 proteins were increased and decreased, respectively, by PM. Exportin-2 (XPO2) was localized to granulosa cells of all follicle stages and was 7.2-fold greater in Atm+/- than WT mice. Cytoplasmic FMR1-interacting protein 1 (CYFIP1) was 6.8-fold lower in Atm+/- mice and was located in the surface epithelium with apparent translocation to the ovarian me...
Source: Biology of Reproduction - Category: Reproduction Medicine Authors: Tags: Biol Reprod Source Type: research