Abstract
Tsetse flies are important vectors of human and animal trypanosomiasis. Ability to reduce tsetse populations is an effective means of disease control. Lactation is an essential component of tsetse’s viviparous reproductive physiology and requires a dramatic increase in the expression and synthesis of milk proteins by the milk gland organ in order to nurture larval growth. In between each gonotrophic cycle, tsetse ceases milk production and milk gland tubules undergo a nearly two-fold reduction in width (involution). In this study, we examined the role autophagy plays during tsetse fly milk gland involution and reproductive output. Autophagy genes show elevated expression in tissues associated with lactation, immediately before or within two hours post-parturition, and decline at 24-48h post-parturition. This expression pattern is inversely correlated with that of the milk gland proteins (lactation-specific protein coding genes) and the autophagy inhibitor fk506-bp1. Increased expression of Drosophila inhibitor of apoptosis 1, diap1, was also observed in the milk gland during involution, when it likely prevents apoptosis of milk gland cells. RNAi-mediated knockdown of autophagy related gene 8a (atg8a) prevented rapid milk gland autophagy during involution, prolonging gestation, and reducing fecundity in the subsequent gonotrophic cycle. The resultant inhibition of autophagy reduced the recovery of stored lipids during the dry (non-lactating) periods by 15–20%. Ecdysone application, similar to levels that occur immediately before birth, induced autophagy, and increased milk gland involution even before abortion. This suggests that the ecdysteroid peak immediately preceding parturition likely triggers milk gland autophagy. Population modeling reveals that a delay in involution would yield a negative population growth rate. This study indicates that milk gland autophagy during involution is critical to restore nutrient reserves and allow efficient transition between pregnancy cycles. Targeting post-birth phases of reproduction could be utilized as a novel mechanism to suppress tsetse populations and reduce trypanosomiasis.
Highlights
Tsetse are important vectors of disease caused by African trypanosomes, known as Sleeping Sickness in humans and Nagana in animals
Inhibiting the process of autophagy prevents the timely transition from the lactation phase to the dry phase, triggering a delay in subsequent pregnancy cycle
This misregulation of milk gland involution leads to an overall decrease in the number of offspring that each female can produce per lifetime
Summary
Tsetse are important vectors of disease caused by African trypanosomes, known as Sleeping Sickness in humans and Nagana in animals. Tsetse females produce a single mature third instar larva during each gonotrophic cycle following a 4–6 day period of intrauterine gestation [1, 2]. These K-strategists produce only a modest 8–10 progeny per female, per lifetime. The contribution of the milk protein transcripts declines to less than 2% of the total output two days after the lactation cycle, at parturition [10]. This drastic transcriptional change in milk protein expression indicates a rapid physiological change in the tsetse milk gland following birth
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