Altered sperm fate in the reproductive tract milieu due to oxidative stress leads to sub-fertility in type 1 diabetes females: A Drosophila-based study

Female sub-fertility, a prominent complication due to Type 1 diabetes (T1D), is generally attributed to disturbances in menstrual cycles and/or ovarian defects/disorders. T1D women, however, are high in oxidative stress, although the impact of the same on their reproduction and associated events remains unknown. Therefore, we assessed the repercussions of elevated oxidative stress on the sperm fate (storage/utilization) in the reproductive tract milieu of T1D females and their fertility using the Drosophila T1D model (Df[dilp1–5]), which lacks insulin-like peptides and displays reduced female fertility. We mated Df[dilp1–5] females to normal males and thereafter examined sperm storage and/or utilization in conjunction with oxidative stress parameters in mated Df[dilp1–5] females at different time points. Also, the impact of antioxidant (Amla or Vitamin C) supplementation on the above oxidative stress parameters in Df[dilp1–5] females and the consequences on their sperm and fertility levels were examined. Df[dilp1–5] females showed elevated oxidative stress parameters and a few of their reproductive tract proteins are oxidatively modified. Also, these females stored significantly fewer sperm and also did not utilize sperm as efficiently as their controls. Surprisingly, amelioration of the oxidative stress in Df[dilp1–5] females' milieu through antioxidant (Amla or vitamin C) supplementation enhanced sperm storage and improved fertility. Hyperglycemia coupled with elevated oxidative stress within the female reproductive tract environment affects the sperm fate, thereby reducing female fertility in T1D. In addition, these findings suggest that antioxidant supplementation may substantially aid in the mitigation of sub-fertility in T1D females.