Research Paper Volume 3, Issue 8 pp 782—793

Mechanisms of chemotherapy-induced human ovarian aging: double strand DNA breaks and microvascular compromise


Figure 1. Induction of double strand DNA breaks in human primordial follicles by doxorubicin. γH2AX-positive (black arrows) and negative (white arrows) primordial follicles in human ovarian cortical pieces after in vitro culture with doxorubicin doses of 1-100 mg/ml for 24 or 72h. A-C) Doxorubicin induces DSBs in a dose-dependent fashion after 24h of culture. Note the massive induction of DSBs in primordial follicles after 24h culture with doxorubicin 100 mg/ml. D) Vehicle control at 72h. E-G) Doxorubicin treatment at 100 mg/ml for 72h also causes ovarian tissue necrosis along with massive γH2AX expression in stromal cells. H) Negative control, secondary antibody omitted. I) Induction of DSBs was positively correlated with the dose of doxorubicin after 24-72h culture (Spearman's rank correlation coefficient: 0.967; p<0.001). J) High number of γH2AX-positive primordial follicles in a xenograft from a SCID mouse treated with 10mg/kg doxorubicin. K) Vehicle-treated (control) human ovarian tissue xenograft.

# Significantly different from the control 24h

* Significantly different from the control