| Background Hypospadias and cryptorchidism were the most commoncongenital genital malformations, the incidences of them were high, andit showed an increase tendency in recent years.These two kinds of diseaseboth need surgery, and the effect of suegery is not well. It ofen come withneopathy, or cannot recover reproductive function. We have found thatpregenant rats exposed to DEHP could induce hypospadias andcryptorchidism in the offsprings. On this base, we will further more explorethe pathogenesis of hypospadias and cryptorchidism in this study in order toprovide theoretical envidence of these two disease.Objective To investigate the expression of extracellularsignal-regulated kinase (ERK) in the congenital malformation penis andtesticulus of fetal rats induced by maternal exposure to di-(2-ethylhexyl)phthalate (DEHP) in order to explore the etiology of congenital genitalmalformation. Methods40timed-pregnant rats were given DEHP by gastricintubation at doses of0(soybean oil),750mg/kg body weight/day fromgestation day (GD)12to19to establish a congenital genital malformationrat model. In each group, half of them (10rats) were raised to delivernaturally, and live male pups were counted, the male pups’ weight and theiranogenital distance (AGD) were measured on postnatal day (PND)1/3/7/14/21/30, and the hypospadias and cryptorchidism was observed onPND30. The left (10rats) were caesarean delivered at GD20, and fetal ratspenis and testiculus were collected for real-time quantitative polymerasechain reaction (qPCR) and immunochemistry to determine the mRNAexpression and protein phosphorylation level of ERK.Results The10pregnant rats of DEHP group had82offsprings with39male; the10pregnant rats of normal control group had119offspringswith62male, the number of the offsprings and the male ones weresignificantly reduced in the DEHP group compare with the normal controlgroup (P<0.01). Check the male offsprings’ bodyweight and AGD ondifferent days, the male offsprings’ bodyweight and AGD of the DEHPgroup were6.32±0.60g and3.91±0.57mm as the normal control group were6.95±0.14g and4.67±0.20mm on PND1; the male offsprings’ bodyweightand AGD of the DEHP group were8.11±0.95g and5.42±0.67mm as thenormal control group’s were9.98±0.29g and6.02±0.27mm on PND3; themale offsprings’ bodyweight and AGD of the DEHP group were 14.02±2.39g and6.76±0.73mm in the DEHP group as the normal controlgroup’s were18.78±0.23g and8.43±0.46mm on PND7; the maleoffsprings’ bodyweight and AGD of the DEHP group were27.03±3.01gand10.20±0.80mm as the normal control group’s were32.98±0.69g and12.05±0.40mm on PND14; the male offsprings’ bodyweight and AGD ofthe DEHP group were42.48±4.61g and15.14±1.17mm as the normalcontrol group’s were52.33±1.39g and18.16±0.73mm on PND21; and thesame dates of the DEHP group were66.08±8.67g and20.88±1.36mm asthe normal control group’s were84.82±7.56g and23.73±1.09mm on PND30. The male offsprings’ bodyweight and AGD of the DEHP group weresignificantly reduced when compared with the normal control group ondiffrernt days.11hypospadiac rats were observed in the DEHP group andthe incidence was28.2%, significantly higher than the normal control group(P<0.01), in which no hypospadiac rat was observed.20cryptorchid ratswere observed in the DEHP group and the incidence was51.3%(unilateralcryptorchidism incidence was10.3%as bilateral one was41.0%), alsosignificantly higher than the normal control group (P<0.01), in which nocryptorchid rat was observed. The expression of phosphorylated ERK in thefetal rat penis of DEHP group showed an increasing trend while the totleERK appears the same.The results of the q-PCR of ERK1and ERK2related to GAPDH were0.82±0.13and1.32±0.33in the normal controlgroup while in the DEHP group were1.09±0.18and1.81±0.22, significantly increase of ERK1and ERK2mRNA was observed (P<0.05).The expression of phosphorylated ERK in the fetal rat testiculus of DEHPgroup and the normal control group showed no significantly difference.Conclusion Our results preliminary indicate that the aberrated ERKmay associated with the formation of hypospadias through the methods ofspatial regulation. Cryptorchidism and the upregulated ERK showed nonotably correlativity. |
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