Effects of Bisphenol A on Ovary Development and VEGF Expression of Female Rat Offsprings

目的:探讨大鼠妊娠期接触双酚A(BPA)对雌性子代卵巢发育和血管内皮生长因子(VEGF)蛋白表达的影响.方法:实验组于SD母鼠妊娠第7～20日分别灌胃给予0.005mg/kg、0.05mg/kg、0.5mg/kg、2.5mg/kg BPA,阴性对照组给予0.5mg/kg溶剂,阳性对照组给予0.05mg/kg己烯雌酚,每组8～10只.观察雌性仔鼠的阴道开口时间,分别于出生后30d、60d(分别相当于人青春期前和成年期)处死仔鼠,称重卵巢,光学显微镜观察卵巢组织学变化,ELISA检测血清雌、孕激素水平,Western blotting检测卵巢VEGF蛋白的表达.结果:BPA 0.05mg/kg、0.5mg/kg、2.5mg/kg组仔鼠阴道开口时间明显缩短,2.5mg/kg组青春期前仔鼠卵巢脏器系数明显升高,BPA 0.05mg/kg、0.5mg/kg、2.5mg/kg组卵巢出现多囊样病变,BPA 0.5mg/kg、2.5mg/kg组青春期前仔鼠血清雌、孕激素水平明显升高,BPA 2.5mg/kg可导致青春期前仔鼠卵巢VEGF蛋白表达明显升高.结论:母体妊娠期接触BPA可导致青春期前雌性仔鼠卵巢出现多囊样病变,但对成年雌性仔鼠卵巢无明显影响.     

青春期雄性小鼠双酚A暴露对生殖功能及子代性别比的影响

目的:研究双酚A(BPA)暴露对青春期雄性小鼠成年后生殖功能及对子代的影响。方法:21日龄C57BL/6J雄性小鼠每日腹腔注射BPA 50 mg/kg连续7 d,35 d后检测成年后雄鼠附睾尾精子数量、精子畸形率、睾丸组织学变化;与正常雌性小鼠配种,观测生育力指标以及仔鼠的出生情况。结果:BPA暴露能引起小鼠附睾尾精子数量下降20.6%(P0.01);精子畸形率增加9.65%(P0.05);睾丸组织结构异常;BPA暴露对雄性小鼠成年后的生育力没有明显影响;但能引起子代雄∶雌出生性别比升高。结论:青春期雄鼠BPA暴露能引起成年雄鼠生精功能下降,仔小鼠雄性比例增加。     

青蒿水提物对小鼠生殖功能及胎鼠生殖发育的影响

目的:观察青蒿水提物对雌性小鼠生殖功能及胚胎发育的影响。方法:80只健康昆明种雌小鼠随机分成4组,实验组连续14 d分别腹腔给予青蒿水提物20 mg/kg(低剂量组)、100 mg/kg(中剂量组)和500 mg/kg(高剂量组),对照组以等量生理盐水代替,然后与雄鼠合笼,同组内一半雌鼠继续给药至交配成功后14 d处死;另一半雌鼠在受精后继续给药35 d,自然分娩,检测青蒿水提物对各组母鼠生育能力和胎仔生长发育的影响。结果:高剂量组青蒿水提物可以使孕鼠的胎仔数以及仔鼠平均体质量、胎盘质量下降,吸收胚胎数增加;但对雌鼠的交配指数、生育指数、活产指数及对出生仔鼠的存活指数、生长指数均无明显影响(P>0.05)。结论:青蒿水提物对孕鼠胚胎有影响,但对雌鼠的其它生殖功能无明显毒性作用。     

出生早期使用二甲双胍对宫内高雄激素化仔鼠成年后卵巢CYP17的影响

目的:使孕中期雌鼠暴露于高雄激素状态,观察其雌性子代在出生早期使用二甲双胍后,血清激素水平及卵巢组织中17a-羟化酶(CYPl7)表达情况。方法:选择孕16～18天的Wistar雌性大鼠,在颈背部皮下注射丙酸睾丸酮,连续3天。孕鼠分娩后第2天予以二甲双胍灌胃,连续14天。雌仔鼠生长至成年后作为实验对象,观察血清激素水平,运用免疫组化及蛋白印迹方法,检测卵巢组织中CYPl7蛋白的表达。结果:(1)孕中期雌鼠经雄激素处理后,所生雌鼠卵巢呈多囊样改变,睾酮、LH水平显著升高(P<0.05),FSH、INS水平没有明显变化;卵巢组织中CYP17表达显著增强(P<0.05)。(2)子代雌鼠予以二甲双胍干预后卵巢多囊样改变缓解,睾酮、LH水平下降;卵巢组织中CYP17表达减弱。结论:孕中期雌鼠注射丙酸睾丸酮,所生雌鼠表现为高雄激素血症、高LH,卵巢囊性化改变符合人类PCOS特征,二甲双胍可通过调节血清激素水平和卵巢内CYPl7的表达改善宫内高雄激素化仔鼠的临床症状。     

双酚A对卵巢卵泡发育和雌性生殖系干细胞的影响

目的探讨双酚A(BPA)对小鼠卵巢卵泡发育及雌性生殖干细胞(FGSC)的影响及其机制。方法雌性小鼠腹腔注射不同BPA(12.5、25和50mg/kg/d)浓度,同时对小鼠FGSC进行体外培养,进行细胞增殖、凋亡及蛋白质组学分析。结果 BPA处理后中剂量组、高剂量组中原始卵泡、初级卵泡、窦卵泡和闭锁卵泡数低于对照组(P0.05)。50和100μM BPA处理组与对照组相比,FGSC数量无统计学差异(P0.05)。150μM BPA组在48和72 h时FGSC的数量明显减少(P0.05);150μM BPA处理组的凋亡率高于其他各组(P0.05)。BPA-处理卵巢中(SLTM)蛋白表达低对照组(P0.05)。结论 BPA对卵巢卵泡发育和雌性生殖系干细胞具有抑制作用。     

妇科养荣胶囊改善化疗所致小鼠卵巢功能损伤的效果

目的:观察妇科养荣胶囊(Fu Ke Yang Rong capsule,FKYRC)对卵巢损伤小鼠卵巢储备功能和生育力的保护作用。方法:通过成年雌性小鼠一次性腹腔注射120 mg/kg环磷酰胺和10 mg/kg白消安建立卵巢损伤小鼠模型,于造模前7 d至造模后60 d每日对卵巢损伤小鼠用高、中、低剂量(6 g/kg、4 g/kg和2 g/kg)FKYRC(H组、M组、L组)连续灌胃给药;同时,于造模前7 d一次性皮下注射给予Gn RHa(38 mg/kg)作为阳性对照组(Gn RHa组),用生理盐水(0.2 m L/d)代替FKYRC连续灌胃作为卵巢损伤对照组(模型组),另设正常对照组:非卵巢损伤正常小鼠腹腔注射给予等体积DMSO(NC组)。分别于造模后30 d和60 d取材,计数卵巢组织中各级卵泡数量,检测血清E2、FSH、抑制素B(INHB)和抗苗勒氏管激素(AMH)水平,检测卵巢组织中翼状螺旋/叉头转录因子2(FOXL2)和AMH蛋白的表达水平。并观察造模60 d后各组妊娠率和窝仔数。结果:各给药组和模型组小鼠血清E2低于NC组(P0.05),但FSH水平组间无统计学差异(P0.05)。造模各组卵泡数明显低于NC组(P0.05),且H组和Gn RHa组造模后60 d时卵巢组织中窦前卵泡与窦卵泡数较高,但各干预组与模型组比较无统计学差异(P0.05)。模型组小鼠卵巢组织中FOXL2和AMH蛋白表达水平显著低于各FKYRC干预组(P0.05),H组的妊娠率(80.00%)显著高于模型组(36.36%)(P0.05)。结论:连续FKYRC(6 g/kg)给药60 d后可明显改善烷化剂所致卵巢损伤小鼠的卵巢储备功能和生育能力,其机制可能与上调颗粒细胞中FOXL2和AMH的表达水平相关。     

RU486对OHSS模型大鼠血管内皮生长因子产生的作用

目的:探讨RU486对卵巢过度刺激综合征(OHSS)模型大鼠血管内皮生长因子(VEGF)产生的作用。方法:30只22日龄雌性大鼠,从22日龄起每天皮下注射10IUPMSG连续4d,26日龄时皮下注射100IUhCG,建立OHSS模型。在27日龄将上述大鼠随机分成5组,每组6只。其中4组(A-D组)为实验组,分别皮下注射不同剂量(1mg/kg、5mg/kg、10mg/kg、20mg/kg)的RU486;另一组为对照组不给药。RU486注射48h后,采用酶联免疫吸附试验方法测定血清和腹腔冲洗液中VEGF水平;采用免疫组织化学法和逆转录聚合酶链反应技术检测卵巢组织VEGF蛋白质和mRNA的表达。结果:B组和C组的血清VEGF水平分别为55.00±14.13pg/ml和49.67±17.44pg/ml,均显著低于对照组(76.17±18.19pg/ml)(P<0.05)。同样,B组和C组的腹腔VEGF水平分别为10.43±6.80pg/ml、10.30±5.82pg/ml,也均显著低于对照组(17.12±1.71pg/ml)(P<0.05)。B组和C组的卵巢组织VEGF蛋白质和mRNA的表达显著低于对照组(P<0.05)。结论:适当剂量的RU486能够降低OHSS模型大鼠VEGF的产生。     

胚胎期氟他胺暴露对SD大鼠支持细胞增殖和成熟的影响

目的:探讨胚胎期暴露于氟他胺(Flu)对SD雄性仔鼠睾丸支持细胞的影响。方法:将妊娠的SD大鼠随机分为Flu组和正常组,Flu组自妊娠后第12～21日每日皮下注射25 mg/kg Flu以建立生殖发育障碍模型,正常组不作任何处理。分别在雄性幼仔出生后第13日(PD 13)、PD15、PD 17随机颈椎脱臼法处死幼仔鼠,收集雄仔鼠睾丸组织。免疫组织化学检测雄仔鼠BrdU并计算支持细胞增殖指数,Real-time PCR检测各组雄仔鼠SGP-2基因的表达。结果:随着生长发育,正常组和Flu组雄仔鼠睾丸支持细胞增殖指数均呈下降趋势,PD 17正常组支持细胞增殖已经停止,Flu组PD 13、PD 15、PD 17支持细胞增殖指数升高,明显高于正常组(P<0.05)。PD13 Flu组支持细胞SGP-2 mRNA表达量较正常组无明显差异(P>0.05);PD 15、PD 17 Flu组支持细胞中SGP-2 mRNA表达量明显低于正常组(P<0.01)。结论:胚胎期Flu暴露导致支持细胞增殖期延长、成熟延迟,这可能是导致其生殖细胞发育障碍的重要原因之一。     

环境剂量的双酚A暴露对雄性小鼠生殖功能的影响

目的:研究环境剂量的双酚A(BPA)暴露对雄性小鼠生殖功能的影响及可能的分子机制。方法:84只3周龄C57BL/6J雄性小鼠按体质量随机分为3组,分别为5μg/kg BPA组、50μg/kg BPA组、乙醇溶剂对照组,每组28只。每日灌胃给药1次,连续给药5周后,检测生殖器官脏器指数、附睾尾精子数量、睾丸组织学形态;同期与正常雌性小鼠配种检测雄鼠的生育力。应用MBDq PCR方法检测睾丸中Tnnt2、Tectb基因的甲基化水平变化。结果:1 BPA暴露组与对照组间的生殖系统脏器指数无统计学差异(P0.05)。2 50μg/kg BPA暴露组附睾尾精子数量下降20.1%;睾丸曲细精管管腔中有生精细胞脱落等病理现象。3 BPA暴露组与对照组间的生育率无统计学差异(P0.05),但50μg/kg BPA暴露组每胎平均产仔数下降。4 BPA组睾丸中Tnnt2、Tectb基因的甲基化水平下降(P0.01)。结论:环境剂量的BPA暴露对雄鼠生殖器官脏器指数没有影响,50μg/kg BPA能引起小鼠生精功能下降,睾丸Tnnt2、Tectb基因的甲基化水平下降。     

顺铂诱导化疗损伤性卵巢早衰大鼠模型的探讨

目的:探讨顺铂诱导大鼠化疗损伤性卵巢功能早衰大鼠模型的可行性。方法:成熟雌性SD大鼠腹腔注射低、高剂量顺铂4.5 mg/kg(A组)、6.0 mg/kg(B组)和生理盐水(C组),每周1次,共2次,建立大鼠化疗损伤性卵巢早衰模型。检测血清FSH水平及光学显微镜下计数卵巢最大切面原始卵泡、初级卵泡、闭锁卵泡,阴道涂片观察动情周期变化。结果:A、B组大鼠动情周期均明显长于C组(P<0.05),并呈现剂量相关性改变。B组动情周期天数明显长于注射前(P<0.01);血清FSH水平A组与C组相比无统计学意义(P>0.05),B组明显高于A组和C组(P<0.05)。各顺铂组血清FSH水平注射后均较注射前明显升高(P<0.05)。腹腔注射顺铂后,A组、B组大鼠卵巢最大切面原始卵泡数和初级卵泡数均明显降低(P>0.05),而闭锁卵泡数均明显增加(P<0.05),并呈现剂量相关性改变。结论:顺铂可诱导化疗损伤性卵巢早衰。此化疗损伤性卵巢早衰大鼠模型血FSH明显升高,卵巢组织学衰退性改变与人类化疗损伤性卵巢早衰病变过程相似。     

邻苯二甲酸二(2-乙基)己酯诱发小鼠隐睾与INSL3 mRNA表达的相关性研究

目的:探讨邻苯二甲酸二(2-乙基)己酯(DEHP)诱发小鼠隐睾的分子机制。方法:DEHP分别以低、中、高3个剂量组(100mg/kg、200mg/kg、500mg/kg)灌胃,作用于孕12d(gestationday12,GD12)至产后3d(postnatalday3,PND3)的昆明孕鼠。观察仔鼠隐睾发生率,RT-PCR检测仔鼠睾丸胰岛素样因子3(insulinlikefactor3,INSL3)mRNA表达的相对强度。结果:DEHP可诱发小鼠隐睾,中、高剂量组双侧隐睾发生率分别为16.1%和40.5%,隐睾总发生率分别为25.8%和51.4%;DEHP影响小鼠睾丸组织形态,高剂量组Leydig细胞增生;DEHP下调各实验组小鼠睾丸INSL3mRNA表达水平;PND1、PND5时,DEHP诱发隐睾发生率与INSL3mRNA表达水平呈负相关(r=-1.0,P<0.01),PND15时两者无明显相关性(r=0.50,P>0.05)。结论:DEHP诱发小鼠隐睾并下调睾丸Leydig细胞INSL3mRNA表达水平,隐睾发生率与小鼠一定阶段的INSL3mRNA表达水平有相关性。     

壬基酚孕期经口染毒对F1代昆明小鼠卵巢发育的影响

目的:观察壬基酚孕期暴露对F1代昆明小鼠卵巢发育的影响。方法:交配后7d起,对孕鼠分别每日灌胃壬基酚(NP)(分别为1.2mg/kg、12mg/kg、120mg/kg),对照组灌胃花生油,直至交配后17d,每组7只。子代小鼠出生14d时取卵巢组织病理学检查,计数各级卵泡。观察子代雌鼠观察阴道开口时间和规律动情周期出现时间。子代雌鼠成年3月龄后,于动情前期处死,放免法测定血清E2、FSH浓度,酶联免疫吸附法测定血清抑制素B浓度,取卵巢组织行病理学检查,计数各级卵泡。结果:NP低剂量组阴道开口出现时间提前(P<0.05);低、中剂量组规律动情周期出现时间提前并可见动情周期延长(P<0.05);高剂量组性成熟期始基卵泡数减少(P<0.05),血清抑制素B水平降低(P<0.05);各用药组动情前期血清E2水平降低(P<0.05),FSH水平无明显变化。用药组体质量较对照组明显升高(P<0.05)。结论:壬基酚胎仔宫内暴露,在较低剂量时可影响小鼠的动情起始及动情周期,在较高剂量时可降低卵巢储备,并可影响成年后小鼠雌激素水平。     

邻苯二甲酸二(2-乙基已基)酯致隐睾大鼠表皮生长因子受体表达的实验研究

目的:探讨表皮生长因子受体(EGFR)在隐睾组织中是否存在改变及可能发挥的作用。方法:妊娠SD大鼠随机分为3组,即正常对照组、玉米油对照组和邻苯二甲酸二乙基已基酯(DEHP)实验组,每组10只。玉米油溶剂对照组和DEHP实验组自妊娠第12.5日到妊娠第19.5日分别持续每日经口给予玉米油或DEHP(500 mg/kg)1 ml灌胃,正常对照组不作任何处理。收集出生后20 d的雄性仔鼠睾丸,采用免疫组织化学及Western blotting方法检测EGFR在睾丸组织中的表达。结果:正常对照组和玉米油对照组EGFR的表达无统计学差异(P>0.05);DEHP诱导隐睾组隐睾睾丸组织中EGFR表达与2个对照组相比明显增加,差异有统计学意义(P<0.05)。结论:孕期暴露环境内分泌干扰物DEHP可引起雄性子代发生隐睾,雄性隐睾子代睾丸组织中EGFR表达增加,可能与隐睾引起的远期不育有关。     

Effect of centchroman on the genital organs of the offspring of rats when administered during lactation or during the neonatal period: a comparative study with ethynylestradiol and diethylstilbestrol

Lactating rats were treated with centchroman (1.25 mg/kg body wt. p.o.) or ethynylestradiol (100 micrograms/kg p.o.) daily from day 1 of parturition for 21 days and their offspring were autopsied at 60, 90 and 120 days of age. In the offspring nursed by centchroman treated mothers there was no change in ovarian weight. There was a reduction in their uterine weight; while the luminal epithelium presented a stimulated state, the stroma showed immature state in its histological features. The ovarian and uterine weights and their histology in the offspring of ethynylestradiol treated mothers showed no change. The male offspring of both the groups of rats showed an increase in the weight of genital organs and testis histology presented typical adult features. When centchroman was injected s.c. on 5th postnatal day to female rats (500 micrograms/rat), the ovary remained normal but the uterus revealed estrogen deficient state when they were 60 or 90 days old. Neonatal female rats injected with diethylstilbestrol (10 micrograms/rat) on day 5 showed normal ovary while uterus presented features typical of estrogenic stimulation with small areas of luminal epithelium showing squamous metaplastic changes. The results are discussed comparing the centchroman effects with the reported findings in rats treated with steroidal and triphenylethylene estrogenic compounds during lactation or the neonatal period.     

沙立度胺对大鼠子宫内膜异位组织中VEGF及TNF-α表达的影响

目的:探讨沙立度胺(thalidomide,THD)对大鼠子宫内膜异位组织中血管内皮生长因子(vascular endothelial growth factor,VEGF)和肿瘤坏死因子-α(tumornecrosis factor-alpha,TNF-α)表达的影响。方法:自体移植子宫内膜组织至腹膜,用SD大鼠建立子宫内膜异位症动物模型,3周后随机将建模成功的24只大鼠分为4组,每组6只,其中3组分别腹腔注射沙立度胺5mg/kg、20mg/kg和40mg/kg,模型对照组腹腔注射生理盐水,每天1次,连用4周。治疗结束后处死大鼠,获取异位子宫内膜组织。用免疫组化(SP)法测定VEGF和TNF-α在异位内膜的表达。结果:不同剂量THD给药组VEGF和TNF-α的表达均低于对照组(P0.05),其中以沙立度胺40mg/kg组最为明显。结论:THD可以抑制VEGF和TNF-α表达,从而发挥抗EMs血管生成作用,且其对VEGF和TNF-α表达的影响具有量效关系。     

Bisphenol A induces oxidative stress and decreases levels of insulin receptor substrate 2 and glucose transporter 8 in rat testis

Bisphenol A (BPA), a monomer present in plastics, is known to impair male reproductive functions. Testis executes high-energy-demanding processes such as spermatogenesis and steroidogenesis, the successful accomplishment of which requires several factors including glucose. In this context, we sought to investigate the effects of low doses of BPA on glucose metabolism in the testis of rats and to delineate whether oxidative stress has any role to play in mediating the effects. Bisphenol A was orally administered to rats at dose levels of 0.005, 0.5, 50, and 500 μg/kg body weight for 45 days. A positive control was maintained by orally administering 17β-estradiol at a dose of 50 μg/kg body weight. The levels of plasma glucose and insulin were significantly increased, whereas the testicular glucose level significantly decreased following exposure to BPA and estradiol. A dose-dependent increase in the level of hydrogen peroxide (H?O?) and a significant decline in the activities of hexokinase and phosphofructokinase was observed in the testis of rats treated with BPA. Western blot analyses of insulin receptor substrate 2 (IRS-2) and glucose transporter 8 (GLUT-8) in the testis showed a decline in the levels of these proteins following BPA administration. Immunolocalization of GLUT-8 protein in the testis revealed decreased expression of this protein in spermatocytes and developing spermatids of rats exposed to BPA. The results suggest that persistent exposure to low doses of BPA could disturb glucose homeostasis in the testis and thereby impair testicular functions.     

康普瑞汀磷酸钠对大鼠胚胎发育毒性的研究

目的:探讨抗肿瘤药物康普瑞汀磷酸钠(combretastatin A-4 disodium phosphate,CA4P)对SD孕鼠胚胎发育的毒性作用。方法:80只孕鼠随机分为低剂量(0.15 mg/kg)组、中剂量(0.50 mg/kg)组和高剂量(1.50 mg/kg)组及对照组(生理盐水),每组20只,给药容积均为10 m L/kg。于妊娠第6~15日尾静脉注射给药,每日1次。妊娠第20日解剖孕鼠,检查母体妊娠与胎鼠畸形情况。结果:与对照组比较,高剂量组的着床率、胚胎吸收率均有显著升高,活胎率降低,差异均有统计学意义(P0.05);妊娠后期高剂量组孕鼠体质量增长显著低于对照组,差异有统计学意义(P0.05);中、高剂量组的胎盘质量、活胎体质量、活胎顶臀长以及尾椎数、掌骨数、枕骨数、胸骨数均显著减少(P0.05);各剂量组未见胎鼠外观及内脏畸形。结论:本实验条件下,CA4P对亲代孕鼠未观察到不良反应的剂量水平(NOAEL)为0.50 mg/kg,对胚胎、胎仔发育的NOAEL为0.15 mg/kg,对胎仔致畸作用的NOAEL为1.50 mg/kg。     

The effect of carvacrol on the proinflammatory cytokines,histology, and fertility outcome of cisplatin-related ovarian change in a rat model

ObjectiveIn women, agents used in chemotherapy treatment have side effects such as accelerating follicular depletion and early menopause. Thus, cytotoxic treatments may cause various effects ranging from partial damage to the ovary to premature ovarian failure (POI) and infertility.This study aimed to investigate the protective effect of carvacrol on cisplatin (CIS)-induced reproductive toxicity in female rats.Materials and methodsThe animals were divided to four groups; a healthy group (HG), administered only cisplatin 2.5 mg/kg (CIS); cisplatin 2.5 mg/kg + carvacrol mg/kg (CC-50), and cisplatin 2.5 mg/kg + carvacrol 100 mg/kg (CC-100). In this study, the CC-50 and CC-100 groups were injected with carvacrol at 50 and 100 mg/kg intraperitoneally (IP). The CIS and HG groupswere administered normal saline as a solvent in the same way. One hour afterwardthe CC-50 and CC-100 groups were injected with cisplatin at 2.5 mg/kg IP. This procedure was continued once a day for 14 days. At the end of this period, six rats from each group were euthanized with high-dose anaesthesia. Biochemical (oxidant-antioxidant and proinflammatory cytokines) and histopathological examinations were performed on the right ovarian tissue removed from the dead rats. The remaining (n = 6 in each group) animals were kept in the laboratory with mature male rats for two months for breeding. Rats that didn't give birth within two months were considered infertile. A one-way ANOVA test was used for the biochemical analysis, the a Kruskal Wallis test was used for the histopathological analysis.ResultsIt has been observed that cisplatine causes oxidative stress and inflammatory damage in the ovarian tissue of animals and ultimately causes infertility due to this oxidative stress. While carvacrol significantly suppressed cisplatin-related oxidative stress in ovarian tissue at the 50 and 100 mg/kg doses, it could suppress proinflammatory cytokine increase only at thecytokine increase only at the 100 mg/kg dose. In addition, carvacrol significantly reduced the development of cisplatin-related infertility (from 0 to 83.3%) at a dose of 100 mg/kg.ConclusionThese findings suggest that carvacrol at high doses can reduce the harmful effects of cisplatin on the ovary and improve ovarian reserve in rats.     

Effect of diclofenac sodium administration during pregnancy in the postnatal period.

OBJECTIVE: The present study aimed to investigate the possible postnatal effects on the liver, kidney and testicular tissues of the offspring of rats given diclofenac sodium (DS) during pregnancy. METHODS: At the beginning of the experiment, 80 rats (20 males and 60 females) were raised together for mating purposes. At the end, 50 pregnant rats were obtained and used as the experimental subjects. All pregnant rats were divided into 2 groups, each with 25 rats. The rats of the control group received physiological serum, 1 cm3/kg live weight per day, and the rats of the treatment group were injected with DS, 1 mg/kg live weight per day from the 5th to the 20th day of pregnancy. Four weeks after birth, tissue samples were obtained under anesthesia by perfusion fixation from a total of 40 offspring, 20 (10 males, 10 females) from the control group and 20 (10 males 10 females) from the DS group. Paraffin sections were dyed with hematoxylin eosin and examined under light microscopy. RESULTS: The gestation period was significantly prolonged with DS-treated rats (p < 0.001). A moderate significant enlargement in the periportal area (p < 0.05), sinusoidal dilatation (p < 0.001), bile duct proliferation (p < 0.001), pyknosis in the nucleus of hepatocytes, and vacuolar degeneration in parenchymal cells (p < 0.001) were observed in DS-treated rats. Morphological changes in the liver were found to be similar both in female and male rats. Under light microscopy a similar morphological structure was observed in the kidney and testicular tissues of both the DS-treated and control rats. CONCLUSION: Significant morphological changes were observed in the livers of the offspring whose parents had been treated with DS. No significant differences were observed in liver morphology between the female and male offspring. There were no significant effects of DS on the morphology of the kidney and testis in all offspring.