Allethrin Promotes Apoptosis and Autophagy Associated with the Oxidative Stress-Related PI3K/AKT/mTOR Signaling Pathway in Developing Rat Ovaries

Abstract

The increased concern regarding the reduction in female fertility and the impressive numbers of women undergoing fertility treatment support the existence of environmental factors beyond inappropriate programming of developing ovaries. Among these factors are pyrethroids, which are currently some of the most commonly used pesticides worldwide. The present study was performed to investigate the developmental effects of the pyrethroid-based insecticide allethrin on ovarian function in rat offspring in adulthood. We mainly focused on the roles of oxidative stress, apoptosis, autophagy and the related pathways in ovarian injury. Thirty-day-old Wistar albino female rats were intragastrically administered 0 (control), 34.2 or 68.5 mg/kg body weight allethrin after breeding from Day 6 of pregnancy until delivery. We found that allethrin-induced ovarian histopathological damage was accompanied by elevations in oxidative stress and apoptosis. Interestingly, the number of autophagosomes in allethrin-treated ovaries was higher, and this increase was correlated with the upregulated expression of genes and proteins related to the autophagic marker LC-3. Furthermore, allethrin downregulated the expression of PI3K, AKT and mTOR in allethrin-treated ovaries compared with control ovaries. Taken together, the findings of this study suggest that exposure to the pyrethroid-based insecticide allethrin adversely affects both the follicle structure and function in rat offspring during adulthood. Specifically, allethrin can induce excessive oxidative stress and defective autophagy-related apoptosis, probably through inactivation of the PI3K/AKT/mTOR signaling pathway, and these effects may contribute to ovarian dysfunction and impaired fertility in female offspring.

The role of oxidative stress in ovarian aging: a review

“…Apoptosis in ovarian cells can cause extensive follicular atresia or regression and is considered to be one of the most important mechanisms underlying ovarian aging [19]. OS has been shown to induce apoptosis in ovarian cells by various processes, including exogenous pathways, endogenous pathways and by endoplasmic reticulum stress (ERS) [20][21][22]. In the exogenous pathway, excess ROS in ovarian tissue can activate the Fas/ FasL pathway and recruit caspase-8 (CASP8) to form a death-inducing signaling complex (DISC) with Fas and FasL.…”

Autophagy in Cell Survival and Death

“…Jalouli et al stressed the adverse effect of pyrethroid-based insecticides in developing rat ovaries [4]. Allethrin is one of the most commonly utilized pyrethroids.…”

Carvacrol protects against λ‐Cyhalothrin‐induced hepatotoxicity and nephrotoxicity by modulating oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress, and autophagy

“…Autophagy plays a significant role in λ‐Cyhalothrin toxicity. According to a previous study, pesticides cause autophagy by increasing LC3B expression 78 . In another research, it was shown that the ratio of LC3B II/LC3B I reduced after 0.25 mM of pesticide was administered to N2a cells, but increased significantly while 1 mM of pesticide was administered.…”

“…According to a previous study, pesticides cause autophagy by increasing LC3B expression. 78 In another research, it was shown that the ratio of LC3B II/LC3B I reduced after 0.25 mM of pesticide was administered to N2a cells, but increased significantly while 1 mM of pesticide was administered. Their findings indicate that the impact of pesticides on autophagy varies with treatment dosage.…”