Role of the gene <i>Phlda1</i> in fenvalerate-induced apoptosis and testicular damage in Sprague-Dawley rats

Hong, Ting Ting; Ru, Li; Sun, Lulu; Xu, Jie; He, Mengting; Wang, Wei; Yan, Rui; Tong, Jian; Zhang, Jie

doi:10.1080/15287394.2019.1664584

Cited by 10 publications

(5 citation statements)

References 29 publications

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“…26 In Sprague-Dawley rats, PHLDA1 expression is up-regulated following fenvalerate-induced testicular damage. 27 Jiao et al reported that the exposure of lipopolysaccharides resulted in the significant induction of PHLDA1 in macrophages. 28 Notably, myocardial ischemia-reperfusion injury also evokes increases in PHLDA1 expression in myocardial tissues.…”

Section: Discussionmentioning

confidence: 99%

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Loss of PHLDA1 has a protective role in OGD/R-injured neurons via regulation of the GSK-3β/Nrf2 pathway

Yang¹,

Chen

2021

Hum Exp Toxicol

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Pleckstrin homology-like domain, family A, member 1 (PHLDA1) is a multifunctional protein that plays a role in diverse pathological conditions. However, whether PHLDA1 participates in cerebral ischemia-reperfusion injury has not been reported. The goals of the present work were to assess the possible relationship between PHLDA1 and cerebral ischemia-reperfusion injury. Hippocampal neurons were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate cerebral ischemia-reperfusion injury in vitro, which led to significant increases in the expression of PHLDA1. Cellular functional studies showed that the knockdown of PHLDA1 produced a protective role in OGD/R-injured neurons via the down-regulation of neuronal apoptosis, oxidative stress and proinflammatory cytokine release. On the contrary, the overexpression of PHLDA1 rendered neurons more vulnerable to OGD/R injury. In-depth research revealed that the inhibition of PHLDA1 resulted in the enhancement of nuclear factor erythroid 2 like 2 (Nrf2) signaling in OGD/R-injured neurons. The reactivation of glycogen synthase kinase 3β (GSK-3β) abolished the PHLDA1-inhibition-mediated activation of Nrf2 signaling. Moreover, the restraint of Nrf2 signaling diminished the PHLDA1-knockdown-induced neuroprotective effects in OGD/R-injured neurons. In summary, the data of our work show that the loss of PHLDA1 protects against OGD/R injury via potentiating Nrf2 signaling via the regulation of GSK-3β. This work underscores a potential role of PHLDA1 in cerebral ischemia-reperfusion injury and proposes PHLDA1 as an attractive target for the development of neuroprotective therapy.

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Section: Discussionmentioning

confidence: 99%

“…26 PHLDA1 plays an essential role in mediating fenvalerate-induced cellular apoptosis in rat testes. 27 The up-regulation of PHLDA1 enhances the apoptosis of cardiomyocytes exposed to hydrogen peroxide. 12 Moreover, the inhibition of PHLDA1 alleviates ischemia-reperfusion-induced cardiac apoptosis in vivo .…”

Section: Discussionmentioning

confidence: 99%

Loss of PHLDA1 has a protective role in OGD/R-injured neurons via regulation of the GSK-3β/Nrf2 pathway

Yang¹,

Chen

2021

Hum Exp Toxicol

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“…Research reports in the last 2 years indicate the effect of pyrethroid‐based pesticides in male reproductive physiology. Fenvalerate induced apoptosis and testicular damage, [ 40 ] disruption of ERK/COX‐2 signaling pathway in the testes by permethrin, [ 41 ] alterations in the expression of testicular nucleotidase gene by lambda‐cyhalothrin, [ 42 ] antiandrogenic activity of cypermethrin in Sertoli cells, [ 43 ] disruption of steroidogenesis in the male rats by deltamethrin, permethrin, esfenvalerate, and cypermethrin [ 44‐46 ] and lambda‐cyhalothrin delayed pubertal development in rats [ 24 ] are some of the manifestations observed due to pyrethroid toxicity. This study was conducted to provide additional evidence on the toxic effects of pyrethroids when administered at doses relevant to human exposure through food.…”

Section: Discussionmentioning

confidence: 99%

Effect of long‐term treatment with a mixture of pyrethroids on the expression of genes that govern male germ cell production in rats

Ravula

Yenugu

2020

J Biochem & Molecular Tox

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Humans are exposed to pyrethroid‐based pesticides through agricultural produce. In this study, male Wistar rats were orally treated for 9 to 12 months with a mixture of pyrethroids that is equivalent to one‐fifth (high dose; HD) or one‐twenty fifth (low dose; LD) of the amount of pyrethroids present in the cereals and rice consumed by an average Indian. In rats treated for 9 months, the spermatogenesis‐associated genes Abp, Ar, Cd9, Dax1, Dazap1, Ddx3y, Gdnf, Gfra1, Grth, Inhb, Ovol1, P1, Plzf, Pygo2, Scf, Tgfb1, Tp1, Tp2, and Vim1 were downregulated in both LD and HD groups. In rats treated for 12 months Gdnf, Hsf2, Inhb, Tgfb1, Thy1, and Ybx2 expression was downregulated in both LD and HD groups. Steroidogenesis‐associated genes 17‐β‐Hsd, Gata4, Hmgcr, Hmgcs1, Pde4b, and Tspo gene expression were reduced in both LD‐ and HD‐treated groups treated for 9 months. In 12‐month‐treated rats, Creb1 expression decreased in both LD and HD groups. The epigenetic reprogramming‐associated genes, Dnmt1, Dnmt3a, Dnmt3b, Hdac10, Hp1bp3, Kat3a Kat3b, Mch2ta, Ncoa7, and Sirt1 were downregulated in both HD and LD groups of 9‐months‐treated rats. In rats treated for 12 months, Hdac10, Mch2ta, Ncoa7, and Sirt1 messenger RNA levels decreased in both the HD and LD groups. Thus, we demonstrate that long‐term exposure to a mixture of pyrethroids caused aberrations in the transcriptome of factors involved in sperm production and development.

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“…In this study, we report that exposure of male rats to a mixture of pyrethroids (at doses equivalent to that present in the amount of rice and vegetables) resulted in decreased fecundity, sperm count and activity of 13β‐HSD enzyme. The effect of pyrethroids on male fertility was reported and a few of them published in the recent past indicate: antiandrogenic effects of cypermethrin (Wang et al, 2019); susceptibility to transgenerational diseases of male reproductive tract by permethrin (Thorson et al, 2020); testicular damage and compromised sperm quality and quantity by deltamethrin (Ben Slima et al, 2017); cylahothrin mediated delay in Leydig cell function (Li et al, 2018); desensitization of androgen receptor by cypermethrin (Ding et al, 2020); perturbations in the neurohormone levels by fenvalerate (H. Zhang et al, 2020); and testicular toxicity by permethrin, fenpopathrin, deltamethrin, fenvalerate and beta‐cypermethrin (Atef et al, 2020; Barkallah et al, 2020; Ham et al, 2020; Hong et al, 2019; Y. Zhang et al, 2020). These reports studied the toxic effects using a single pyrethroid or at doses that are not akin to real time settings.…”

Section: Discussionmentioning

confidence: 99%

“…Mean ± SD is presented for the values obtained for each parameter. Statistical significance of p < 0.05 between control and treated groups is indicated by * symbol testicular toxicity by permethrin, fenpopathrin, deltamethrin, fenvalerate and beta-cypermethrin (Atef et al, 2020;Barkallah et al, 2020;Ham et al, 2020;Hong et al, 2019;. These reports studied the toxic effects using a single pyrethroid or at doses that are not akin to real time settings.…”

Section: Discussionmentioning

confidence: 99%

A mixture of pyrethroids induces reduced fecundity and increased testicular genotoxicity in rats

2022

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To achieve crop protection and higher agricultural yield, pesticides are used; and among them pyrethroid based ones are the most preferred choice because of their specificity on the pests. Uncontrolled use of pesticides resulted in contamination of food products. Presence of residual amounts of pyrethroids was reported in agricultural products sold in Indian market, indicating that humans are constantly exposed to these chemicals through food on a routine basis. Studies that determine the toxic effects of pyrethroids at doses equivalent to human exposure are rare. We orally administered a mixture of pyrethroids (detected in the rice and vegetables of Indian market) to male rats for 15 months to mimic the long‐term exposure in humans. We observed reduced fecundity, sperm count and 13β‐hydroxysteroid dehydrogenase enzyme activity. The serum concentrations of hormones involved in male reproductive function were altered. Further, testicular genotoxicity as reflected by perturbations in the expression pattern of genes involved in the molecular processes of gametogenesis was evident. Such toxic effects may also be occurring in humans who consume agricultural products that contain residual amounts of pyrethroids on a regular basis throughout their lifetime.

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Role of the gene Phlda1 in fenvalerate-induced apoptosis and testicular damage in Sprague-Dawley rats

Cited by 10 publications

References 29 publications

Loss of PHLDA1 has a protective role in OGD/R-injured neurons via regulation of the GSK-3β/Nrf2 pathway

Loss of PHLDA1 has a protective role in OGD/R-injured neurons via regulation of the GSK-3β/Nrf2 pathway

Effect of long‐term treatment with a mixture of pyrethroids on the expression of genes that govern male germ cell production in rats

A mixture of pyrethroids induces reduced fecundity and increased testicular genotoxicity in rats

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