Suppression of lactation-induced oxidative stress in tsetse flies is critical to the prevention of reproductive senescence

Reproduction is one of the most energetically demanding processes that females undergo throughout their lifetime.  Elucidation of the role of reproduction on female health and longevity has yielded conflicting results, specifically if oxidative stress is important to this process.  We utilized the viviparous tsetse fly to determine if high metabolic demand during milk production alters reproductive senescence and longevity.  Tsetse flies have a minimal period of reproductive senescence and changes in oxidative stress markers during the reproductive cycle even with over 50% of transcripts are devoted to milk production during tsetse lactation.  We noted an increase in antioxidant enzyme (AOE) genes and activity during tsetse lactation, birth and involution that were localized within tsetse reproductive tissues, particularly the milk gland.  Suppression of this AOE response during lactation yielded reduced fecundity in subsequent reproductive cycles, extremely low fecundity late in life and reduced longevity. The reduced fecundity is at least in part due to dysfunction in the milk gland. Treatment of virgin females with hydrogen peroxide at pregnancy intervals yielded reduced survival that was further exacerbated by AOE knockdown.  AOE expression during lactation and involution appears critical in the prevention of oxidative damage associated with the rapid generation of nutrients within the milk gland, birth and breakdown of the milk gland during involution. Without this AOE response lactation in subsequent generations is incapable of meeting the energetic demands of the developing intrauterine larva.  This oxidative stress response during tsetse milk production is likely a critical factor in the transition from providing minimal to no nutrients for juvenile progeny to supplying all nutrients required for juvenile development.