Cypermethrin exposure during puberty disrupts testosterone synthesis via downregulating StAR in mouse testes

Wang, Hua; Wang, Qun; Zhao, Xingxu; Liu, Ping; Meng, Xiu-Hong; Yu, Tao; Ji, Yan-Li; Zhang, Heng; Zhang, Cheng; Zhang, Ying; D, Xu

doi:10.1007/s00204-009-0479-y

Cited by 75 publications

(40 citation statements)

References 33 publications

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“…Earlier studies showed histopathological changes in the testes, disorganization of spermatogenesis, reduced diameter of tubules, sperm counts and testosterone levels in rats, mice and rabbits following treatment with CYP 3,4,6,[9][10][11]17 . Since these studies did not focus on alterations if any in different stages of spermatogenesis, whether CYP targets specific stages or affects all the stages could not be ascertained form these reports.…”

Section: Discussionmentioning

confidence: 98%

“…An increase in the height of the seminal gland epithelium and epithelial cell proliferation were found following administration (ip) of 485 mg CYP/kg bw for 1,9,17,26, and 34 days in mice 8 . Daily treatment with 20 mg/kg bw beta-CYP by gavage for 35 days impaired reproductive function by inducing oxidative stress 9 and daily treatment with 25 mg/kg bw CYP during puberty (postnatal day 35 to 70) disturbed testosterone synthesis via downlregulating the expression of steroidogenesis acute regulatory protein (StAR) and steroidogenic enzymes in the testes in mice 10 . Exposure to 15 or 30 mg beta-CYP/kg bw in rats for 15 days caused disruption in spermatogenesis 11 .…”

Section: Introductionmentioning

confidence: 99%

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Endocrine disruptive action of cypermethrin in male mice

Al-Hamdani

Narasinhachary

2011

Toxicol. Environ. Health Sci.

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Administration (intubation) of cypermethrin to adult male mice for 6 and 12 weeks on alternate day in 3 dose levels,1.38, 2.76 and 5.52 mg/kg body weight (bw) corresponding to 1/476, 1/238 and 1/119 of LD 50 dose respectively, caused degeneration of germinal epithelium, vacuolization of seminiferous tubules and a significant decrease in i) weight of the body, testes and epididymis, ii) diameter of the seminiferous tubules and epididymal ducts and iii) serum levels of testosterone these parameters were restored to control levels, six weeks after cessation of 1.38 mg/kg bw treatment (both durations) but not after 5.52 mg/kg bw treatment within the same period. The results reveal for the first time that chronic exposure even to 5.52 mg/kg bw i.e. up to 1/119 of LD 50 induces histopathological alterations and impairment in spermatogenic and steroidogenic activities of the testis which are not reversible within a period of 6 weeks.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Endocrine disruptive action of cypermethrin in male mice

Al-Hamdani

Narasinhachary

2011

Toxicol. Environ. Health Sci.

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“…Previous studies have reported that Zn plays important roles in the production, storage and secretion of a number of hormones including testosterone (26,36). Studies in animal models as well as clinical studies have demonstrated that hypogonadism is a prominent feature of Zn deficiency in humans and animals (37,38); however, the underlying mechanisms responsible for these endocrine effects observed in Zn deficiency remain unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Testosterone is essential for spermatogenesis, fertility and the maintenance of the male phenotype (25). StAR protein and testosterone biosynthetic enzymes play critical roles in the synthesis of testosterone in Leydig cells (26)(27)(28). Double immunofluorescence staining for ZnT7 and StAR was performed to analyze the distribution and localization of both proteins in the mouse testis.…”

Section: Colocalization Of Znt7 and Star In The Leydig Cells Of Mousementioning

confidence: 99%

A potential role for zinc transporter 7 in testosterone synthesis in mouse Leydig tumor cells

Chu

Chen

Zhang

et al. 2016

International Journal of Molecular Medicine

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Abstract. Previous studies have demonstrated that zinc (Zn) is an essential trace element which is involved in male reproduction. The zinc transporter (ZnT) family, SLC30a, is involved in the maintenance of Zn homeostasis and in mediating intracellular signaling events; however, relatively little is known regarding the effect of ZnTs on testosterone synthesis. Thus, in the present study, we aimed to determine the effect of Zn transporter 7 (ZnT7) on testosterone synthesis in male CD-1 mice and mouse Leydig cells. The findings of the present study revealed that the concentrations of Zn in the testes and Leydig cells were significantly lower in mice fed a Zn-deficient diet compared with the control mice fed a Zn-adequate diet. In addition, ZnT7 was principally expressed and colocalized with steroidogenic acute regulatory protein (StAR) in the Leydig cells of male CD-1 mice. ZnT7 expression was downregulated in the mice fed a Zn-deficient diet, which led to decreases in the expression of the enzymes involved in testosterone synthesis namely cholesterol side-chain cleavage enzyme (P450scc) and 3β-hydroxysteroid dehydrogenase/D5-D4 isomerase (3β-HSD) as well as decreased serum testosterone levels. These results suggested that Znt7 may be involved in testosterone synthesis in the mouse testes. To examine this hypothesis, we used the mouse Leydig tumor cell line (MLTC-1 cell line) in which the ZnT7 gene had been silenced, in order to gauge the impact of changes in ZnT7 expression on testosterone secretion and the enzymes involved in testosterone synthesis. The results demonstrated that ZnT7 gene silencing downregulated the expression of StAR, P450scc and 3β-HSD as well as progesterone concentrations in the human chorionic gonadotrophin (hCG)-stimulated MLTC-1 cells. Taken together, these findings reveal that ZnT7 may play an important role in the regulation of testosterone synthesis by modulating steroidogenic enzymes, and may represent a therapeutic target in testosterone deficiency.

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“…In recent years, researchers have been demonstrating that some pyrethroid compounds are capable of interfering with the endocrine system of some animal species including man and therefore can be considered as ED chemicals (MEYER, 1999;WANG et al, 2009;ABRASCO, 2015;CRUZ;OLIVEIRA, 2015). For many ED pesticides and medical conditions, insufficient data are available to prove or disprove a link with an individual compound or group of compounds (MARTIN et al, 2007).…”

Section: Endocrine Disruptors: Cypermethrinmentioning

confidence: 99%

Cypermethrin exposure and effects on the reproductive male system: a literature review

2017

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The use of pesticides has become a major problem of public and environmental health in the world and especially in Brazil, which consumes tons of these compounds every year since the 50s. Among the pesticides, cypermethrin is an admittedly widely used synthetic pyrethroid due to its broad spectrum of action, resulting in its massive use in the agricultural sector. Epidemiological data show a considerable increase in the incidence of diseases in the male reproductive tract among them, the decline of sperm quality in various regions of the world, with consequent increase in demand for assisted reproduction services and increased incidences of cryptorchidism, hypospadias and testicular tumors. In recent years, researchers have shown that some pyrethroid compounds are capable of interfering with the endocrine system of animal species, including human being and therefore can be considered as endocrine disrupters. They can result in a deviation from normal homeostatic control or reproduction by interfering with the synthesis, secretion, transport, binding, action or elimination of natural hormones. It has been reported that endocrine disruptors may be responsible for the decline in sperm density and increase in hypospadias, cryptorchidism and testicular Revinter, v. 10, n. 03, p. 18-38, out. 2017. P á g i n a19 | 38 cancer in humans. In this sense, experimental studies have shown that cypermethrin acts indirectly on male gametogenesis, interfering with the synthesis of testosterone.Other disorders induced by cypermethrin are also reported, as structural changes of the seminiferous tubules, morphological changes in germ cells and sperm as well as a reduction in their count in semen. This paper aims to demonstrate aspects of endocrine disruption in the male reproductive system related to cypermethrin exposure, using data from animal studies (in vivo) and biological samples of human beings (in vitro). células germinativas e espermatozoides, bem como uma redução na sua contagem no sêmen. Este trabalho tem como objetivo demonstrar aspectos da desregulação endócrina no sistema reprodutor masculino relacionados à exposição à cipermetrina, utilizando dados de estudos animais (in vivo) e amostras biológicas de seres humanos (in vitro). Palavras

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Cypermethrin exposure during puberty disrupts testosterone synthesis via downregulating StAR in mouse testes

Cited by 75 publications

References 33 publications

Endocrine disruptive action of cypermethrin in male mice

Endocrine disruptive action of cypermethrin in male mice

A potential role for zinc transporter 7 in testosterone synthesis in mouse Leydig tumor cells

Cypermethrin exposure and effects on the reproductive male system: a literature review

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