| Background: With the development of modern industry, the adversehealth effects of environmental endocrine disruptors on human and animalshave arisen great concern worldwide. Pre-study demonstrated that somewidely distributed exogenous agents (esp. synthetic chemicals) exist widelyin the environment and can concentrate in the human body throughmultiple routes of exposure. It has been hypothesized that they mayinterfere with the production, release, transport , metabolism, binding,biologic action and elimination of natural hormones. By presenting theeffects of mimicking or inhibiting the action of natural ligands, they caninduce a series of adverse effects such as declined of male reproductivefunction and increased in incidence of urogenital anomalies and cancers.These compounds are called environmental endocrine disruptors (EEDs).Recently DEHP has been listed as one of the most important EDs, while itis widely used as a prominent plasticizer in plastic and chemical industry. Cryptorchidism affects approximately 4% of newborn males. It canresult in infertility and increase the risk of testicular cancer 20 to 46 times.Nevertheless, pathogenesis of cryptorchidism has not been fully understood.We hypothesized that EDs may play certain role in the increase ofcryptorchidism, whereas the incidence of cryptorchidism and other maleurogenital anomalies increased dramatically in either United States,Europe or industrialized districts of China. Demonstrating the correlationbetween endocrine disruptor DEHP and cryptorchidism and explaining themechanism through animal test are crucial for environmental protectionparticularly,prevention and alleviating the incidence of male urogenitalanomalies and improving the health of human as well. Objective: to study the pathogenesis and key points of theenvironmental endocrine disruptor DEHP induced cryptorchidism in mice. Methods: Healthy pregnant KM mice were randomly divided intofive groups: DEHP was administered to pregnant mice by gavages at500mg/kg.d in 2.5ul of corn oil/g body weight from GD12 to GD19 (thecritical stages of sexual differentiation in mouse). At the same period oftime, DES was administered 100ug/kg.d and flutamide 100mg/kg.d ;Thecorn oil group was given the vehicle only. GD19 after the mothers werekilled, the mice fetuses were quickly removed and placed on ice untildissection. Fetuses were examined under a dissecting microscope, andgubernacula and testes were obtained from male fetuses. The followingend points in each group were recorded: the weight of male pups, sex ratio,location and gross morphology of the testes and the testes-bladder neckrelative distances(TBD); gubernaculums development,cranial suspensoryligament(CSL) residual. Hematoxylin and eosin staining was performed toobserve gonads and gubernacula. Immunohistochemical analyzed theexpression level of androgen receptor (AR),estrogen receptor (ER),actinand proliferating cell nuclear antigen (PCNA) in gubernaculum.gubernaculum tissue culture ex vivo, and observed the development afterrespectively DEHP ,DES and Flu were added in culture medium. Results:(1)GD12-GD19, there were no significant alternations in body weight and sex ratio of fetuses among each group.(2)The testes maldescended with different degree in DEHP group,Flu. group and DES group.(3)In DEHP and Flu. groups gubernaculums could develop normally, but in DES group gubernaculums dysplasia; In Flu. group CSL were remained.(4)In light microscope HE , in DEHP ,DES and Flu. groups all testes seminiferous tubules,spermatogenic cells and sertoli cells existed hypotrophy; Moreover, in DEHP and FLU groups testes Leydig cells hyperplasia markedly.(5)In vivo, Actin and PCNA expression of DES-treated gubernacular cells expressions and AR expression of DEHP-treated and Flu.-treated gubernacular cells all depressed.(6)In cultured gubernaculums, Flu.-treated gubernacular cells AR expression depressed. Conclusions: 1. DEHP is a definite environmental endocrine disruptor, and can induce cryptorchidism in mice. 2. The pathogenesis of DE...
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