| Background: With the development of modern industry, the adverse health effects of environmental endocrine disruptors on human and animals have generated great concern worldwide. Pre-study demonstrated that some widely distributed exogenous agents (exp synthetic chemicals) exist widely in the environment and can concentrate in the human body through multiple routes of exposure. It has been hypothesized that they may interfere with the production, release, transport, metabolism, binding, biologic action, or elimination of natural hormones. By presenting the effects of mimicking or inhibiting the action of natural ligands, they can induce a series of adverse effects such as declining male reproductive function or increase in incidence of urogenital anomalies and cancers. Compounds in this class are referred to as environmental endocrine disruptors (EEDs) . In recent years DEHP has been listed as one of the most important EDs, while it is widely used as a prominent plasticizer in plastic and chemical industry.Cryptorchidism affect approximately 4% of newborn males. It can result in infertility and is associated with an 40-fold of increased risk for the development of testicular cancer. Nevertheless, the etiology and endocrine mechanism of cryptorchidism still remain unclear. Since there is a significantly increasing tread in the incidence of male urogenital anomalies (like cryptorchidism) in UnitedStates, Europe and industrialized districts of China, We hypothesized that EDs may be responsible for this phenomenon. Thus, through studies on the correlation between important endocrine disrupter DEHP and cryptorchidism, it becomes necessary to reducing environmental pollutions, prevent or alleviate theincidence of male urogenital anomalies, and improves the health of human as well.Objective: to study the effect of environmental endocrine disruptor DEHP on the incidence of cryptorchidism in mice, and explore the associated mechanisms.Methods: Healthy pregnant KM mice were randomly divided into five groups; DEHP were administered to pregnant mice by gavages at 100 or 500mg/Kg/d in 2.5ul of corn oil/g body weight from GD12 until PND3 (the critical stages of sexual differentiation in mouse) . The DES group was administered 100 g DES/Kg/d at the same period of time. The corn oil group was given the vehicle only. On PND30 male offsprings were killed, the following end points in each group were recorded: maternal body weight gain during pregnancy, live birth rate, the weight and length of male pups, sex ratio, anogenital distances (AGD) ,location and gross morphology of the testes and epididymides, testicular volume and weight. Histological examinations were performed to evaluate the MSTD and TBS. In each group two specimens were selected for TEM examination and the ultrastructural pathology alterations were observed, plasma testosterone , estradiol , FSH and LH were also measured in male offspring by radio immunoassay ( RIA ) . Immunohistochemical analysis was employed to determine the expressions of AR and ER in testes. About five male pups in each group (cryptorchid mice in DEHP high dose group and DES group) were randomly chosen to be fed up to PND60. The fertility of these male pups was evaluated by copulation. Results:1. Exposure to DEHP during pregnancy has no effects on gestational time, maternal weight gain and live birth rate of the dams.2. There were no significant alternations in body weight and sex ratio of newborn pups among each group. Male offspring in DEHP high dose group and DES group displayed significant decrease of body weights, lengths, AGD at PND30.3. Cryptorchidism was induced in mice of DEHP low dose group DEHP high dose group and DES groups with incidences of 12.5%, 52% and 25.8%; Cryptorchid testicular volume and weight were significantly decreased compared with the non-cryptorchid testis.4. Severe atrophy of seminiferous epithelium and abnormal function of Leydig cells of cryptorchid mice were found in DEHP high dose group and DES group; M...
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