Testicular damage induced by megadoses of pyridoxine

Pyridoxine hydrochloride, 125 mg/kg, 250 mg/kg, 500 mg/kg or 1,000 mg/kg, daily, was intraperitoneally injected into Wistar male rats and its effects on weights and mature spermatid or sperm counts in the testis and the epididymis were investigated. After six weeks administration, weights of the testis and the epididymis in the 500 mg/kg and 1,000 mg/kg groups dramatically decreased and weights of the epididymis in the 125 mg/kg and 250 mg/kg groups also decreased significantly. Mature spermatid counts in the testis and sperm counts in the epididymis decreased in the 500 mg/kg and 1,000 mg/kg groups, and sperm counts in the tail plus body of the epididymis also decreased in the 250 mg/kg group. From these results, it was elucidated that megadoses of pyridoxine induced testicular damage in rats.     

Comparative analysis of antioxidants against cadmium induced reproductive toxicity in adult male rats

Abstract

The present study was conducted to compare and evaluate the potential benefits of three different antioxidants in reversing cadmium (Cd)-induced reproductive toxicity in adult male rats. Rats (n?=?5) weighing 180?±?20?gm were divided into five groups (control, Cd, Cd?+?sulforaphane, Cd?+?vitamin E, and Cd?+?plant extract). Treated groups received CdCl₂ (0.2?mg/kg), sulforaphane (25?µg/rat), vitamin E (75?mg/kg), and plant extract (100?mg/kg) for 15 days. Blood samples and testicular tissues were obtained for estimation of testosterone, Zn, and Cd concentration and daily sperm production/efficiency of sperm production. Cadmium exposure caused a significant decrease in final body weight (p?<?0.0001). The plasma concentrations of Cd were significantly increased and Zn concentration decreased (p?<?0.0001) in the Cd group as compared to the control group. The testicular concentrations of Cd were significantly increased and Zn concentration decreased (p?<?0.0001) in the Cd group as compared to the control group. Cadmium exposure caused a significant decrease (p?<?0.0001) in plasma testosterone concentrations and daily sperm production as compared to the control group. More significant effects were observed with Cd+sulforaphane, Cd?+?vitamin E, and Cd?+?plant extract treated groups in slashing Cd-induced toxicity. Present findings suggest that Ficus religiosa and sulforaphane are more powerful antioxidants as compared to vitamin E in reversing the oxidative stress and can have a protective role against Cd induced reproductive toxicity in adult male rats. Part of the mechanism involved in this protective role seems to be associated with the antioxidant properties of these agents in reducing reproductive damage.     

Trials for development of once-a-month injectable, hormonal male contraceptive using dienogest plus testosterone undecanoate: dose standardization, efficacy and reversibility studies in rats

Background

The study was conducted to test the potential of using dienogest (DNG) plus testosterone undecanoate (TU) in rats for development of a once-a-month injectable male hormonal contraceptive.

Study Design

Dose selection studies were initiated with administration of DNG in three different doses of 20, 30 and 40 mg/kg body weight (bw) per week plus TU 25 mg/kg bw once in every 6 weeks. Status of spermatogenesis and sperm count in epididymis was evaluated. The frequency of DNG intervention was later extended to every 2- and 4-week intervals. Mating studies, toxicity and reversibility of spermatogenesis following stoppage of treatment were carried out with DNG 40 mg/kg bw at 4-week intervals.

Results

Complete arrest of spermatogenesis was observed after 60 days of treatment at all doses of DNG (20, 30 and 40 mg/kg bw per week)+TU. However, weights of testis and accessory sex organs (epididymis, prostate and seminal vesicle) declined significantly 60 days post treatment compared to vehicle-treated controls. Epididymis in the treated animals was completely devoid of sperm. When the frequency of DNG injection (20 mg/kg bw) was extended to once every 15 days, a few immotile and decapitated sperm were observed in the epididymis. With TU treatment unchanged, animals receiving DNG (40 mg/kg bw) once either every 2- or 4-week intervals demonstrated good and uniform arrest of spermatogenesis. DNG 40 mg/kg per 4 weeks+TU also demonstrated a significant rise in germ cell apoptosis in the seminiferous epithelium. There was no significant increase in the serum high-density lipoprotein and low-density lipoprotein levels at the end of 120 days of treatment. Following withdrawal of treatment after 60 or 120 days, qualitative restoration of spermatogenesis was rapid in the former compared to the latter.

Conclusion

Dienogest plus TU has the potential for development as a monthly injectable showing reversible hormonal male contraception with good efficacy.     

Gossypol: Its toxicological and endocrinological effects in male rabbits

The effects of different doses of orally administered polyphenolic compound ‘Gossypol’ on semen quality, circulating testosterone (T) and fertility of Dutch-belted male rabbits were studied. Bucks fed daily with 80, 40, 20 mg/kg/day gossypol died within 8–17, 23–35 or 35–84 days, respectively, after inicitation of treatment. Following gossypol treatment at 80, 40 or 20 mg/kg/ day, animals lost appetite and body weight, developed hind limb paralysis, breathing difficulties and collapsed while sitting in their cages. At autopsy, the liver and lungs were found congested while the stomach and intestines contained gases. On the other hand, rabbits fed daily with 10 mg/kg/day gossypol exhibited a survival time ranging from 77 to 250 days. Despite the severe side effects resulting in eventual deaths, weekly semen samples from all treated animals did not show any apparent change in sperm motility, morphology or population. Likewise, gossypol-treated males mated to estrous does exhibited a fertility comparable to vehicle-treated controls. Gossypol fed at a dose of 10 mg/kg/day for up to 35 weeks failed to induce sterility. Male rabbits, fed with either 20 or 10 mg/kg/day gossypol, that survived for longer periods of time had substantially reduced T levels by 12–20 weeks depending upon the dose but were fertile at all times. When the $\text{in vitro}$ release of T from the rat testes mince in the presence of hCG and gossypol was evaluated, an inhibition of T release was recorded. It is concluded that although gossypol has been shown to be an effective antifertility agent in several mammalian species, it failed to exhibit such an effect in Dutch-belted rabbits, although serum T levels were reduced. In addition, gossypol exhibited a wide spectrum of toxicity. The $\text{in vitro}$ study demonstrated that high concentration of gossypol can directly inhibit the T synthesis in the testis.     

吡哆素L-2-吡咯烷酮-5-羧酸酯对大鼠的生殖毒性

目的　研究吡哆素L 2 吡咯烷酮 5 羧酸酯对大鼠的生殖毒性。方法　雄鼠 80只 ,雌鼠 12 4只随机分 4组 ,溶剂对照组 ,3个剂量组吡哆素L 2 吡咯烷酮 5 羧酸酯分别为 4 0 0、80 0和 16 0 0mg/kg。雄鼠交配前连续给药 6 0d ,交配期间继续给药 ;雌鼠交配前连续给药 14d ,交配后给药至妊娠第 14天 ;分别观察生殖毒性试验指标。结果　 4 0 0mg/kg组无明显毒副反应 ,80 0mg/kg组有个别鼠出现后肢麻痹 ,16 0 0mg/kg引起雌雄大鼠后肢麻痹 ,消瘦。吡哆素L 2 吡咯烷酮 5 羧酸酯 16 0 0mg/kg使雄鼠的交配率下降 5 0 % ,有统计学显著性。 80 0mg/kg组生育鼠 7只 ,16 0 0mg/kg组未生育 ,对雄鼠的生育率有统计学显著影响。 80 0mg/kg组雄鼠的精子数为 (5 9 4 0± 2 1 71)× 10 5,16 0 0mg/kg组雄鼠的精子数为 (0 4 0± 0 14 )× 10 5。 80 0mg/kg组活胎数为 (8± 3)只 ,16 0 0mg/kg组无受孕鼠。结论　吡哆素L 2 吡咯烷酮 5 羧酸酯在本实验条件对SD大鼠无致畸性 ,无作用剂量为4 0 0mg/kg ,发育毒性的无作用剂量小于 4 0 0mg/kg。     

壬基酚对仔鼠雄性生殖系统的影响

目的探讨宫内及哺乳期暴露壬基酚对雄性仔鼠生殖系统的影响.方法对28只受孕母鼠从受孕第1天开始灌胃染毒壬基酚(分别为0、50、100和200mg/kg体重),直至仔鼠娩出21d断奶后停止染毒,仔鼠于70日龄剖杀,测定与仔鼠生殖功能相关的各项指标.结果随着壬基酚染毒剂量的增加,70日龄雄性仔鼠的睾丸和前列腺的重量降低,睾丸重分别为2.86、2.98、2.59和2.44g;前列腺重分别为0.26、0.23、0.20和0.19g.每克睾丸日产精子数和每克附睾精子计数也随壬基酚剂量的增加而降低,每克睾丸日产精子数分别为22.46×106、18.46×106、17.43×106和17.26×106;附睾尾精子计数分别为46.85×106、39.74×106、35.57×106和31.36×106.雄性仔鼠包皮分离时间在高剂量组(47.83d)大于对照组(46.31d).结论宫内及哺乳期暴露于壬基酚可使雄性仔鼠睾丸生精功能降低,但睾丸无形态学变化.     

Evaluation of reversible contraceptive activities of Cuminum cyminum in male albino rats

Background

The aim of the present study was to evaluate the contraceptive efficacy of Cuminum cyminum (jeera) seeds in male albino rats.

Study Design

C. cyminum methanol extract (CcMtE) at dose levels of 100 and 200 mg/rat/day was orally administered to male rats for 60 days. The effect of the treatment on reproductive organs and fertility was investigated. Recovery and toxicity studies were also carried out.

Results

C. cyminum methanol extract fed to male rats for 60 days did not cause any alterations in the body weight, whereas the weight of testes, epididymides, seminal vesicles and ventral prostate were significantly reduced (p≤.001). Animals treated with CcMtE showed a marked reduction in sperm density in the cauda epididymis and testes and sperm motility in the cauda epididymis. Reduction in fertility was 69.0% and 76.0% in 100 and 200 mg/rat/day dose levels, respectively. The circulatory hormones were also reduced significantly. Testicular biochemical analysis of protein, sialic acid, glycogen, ascorbic acid and fructose indicated a marked decline, whereas testicular cholesterol content was significantly increased, which showed altered biochemistry of the reproductive organs. After CcMtE treatment, significant decreases (p≤.001) were observed in the number of testicular cells (i.e., spermatogonia, primary spermatocytes [preleptotene and pachytene], secondary spermatocytes and round spermatids); nonsignificant change was observed in the Sertoli cell count. The treatment had no effect on levels of serum protein, cholesterol, bilirubin, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea and hematological indices.

Conclusions

The present study shows that C. cyminum treatment resulted in the inhibition of spermatogenesis and fertility without producing apparent toxic effects.     

乙酰唑胺对大鼠精子发生和成熟的影响

目的:研究碳酸酐酶抑制剂对大鼠精子发生和成熟的影响。方法:乙酰唑胺混悬液(40mg/kg)给大鼠灌胃,分别于给药当天、1d和3d处死动物,进行睾丸、附睾称重、苏木素-伊红(HE)染色和光镜下观察分析;附睾尾剪碎计数精子密度、精子活力,染色后计数精子畸形比率;测定附睾管腔液α-葡糖苷酶水平;采用罗丹明(Rh)123荧光探针标记附睾精子,通过流式细胞仪检测线粒体膜电位。结果:给予乙酰唑胺的大鼠精子活力明显降低,畸形率显著增加,附睾精子线粒体膜电位明显降低,附睾管腔液α-葡糖苷酶水平有所下降,但睾丸和附睾无明显病理学改变。结论:碳酸酐酶抑制剂可能通过影响附睾精子成熟,对雄性生殖功能进行调控。     

The effect of high doses of 6-chloro-6-deoxyglucose on the rat

Male rats given 6-chloro-6-deoxyglucose (240 mg/kg/day for 28 days) developed spermatocoeles in their ductuli efferentes or caput epididymides. They had a lower serum triglyceride content than controls ($\text{0.87 ± 0.19}\text{vs}\text{1.84 ± 0.19}\text{mM}\text{,}\text{Mean}\text{±}\text{SEM}\text{;}\text{n}\text{= 6}$) and gained less weight ($\text{2.55 ± 0.37}\text{vs}\text{4.1 ± 0.96}\text{g/day}\text{,}\text{Mean}\text{±}\text{SEM}\text{;}\text{n}\text{= 6}$). There was no effect on female rats which received the same treatment. Spermatocoeles could also be produced by a single dose of 6-chloro-6-deoxyglucose, the threshold dose was between 180 and 240 mg/kg. Glucose oxidation by liver, brain, kidney and diaphragm from rats given 6-chloro-6-deoxyglucose (240 mg/kg/day for 14 days) was the same as in controls but was decreased in seminiferous tubules ($\text{0.32 ± 0.06}\text{vs}\text{0.74 ± 0.02 μ}\text{mol}$ [U-¹⁴C]glucose oxidised to ¹⁴CO₂/g fresh wt/h, Mean ± SEM; n = 3). The activity of glyceraldehyde-3-phosphate dehydrogenase [E.C. 1.2.1.12] in liver, brain, testis or muscle from rats given 6-chloro-6-deoxyg1ucose (24 mg/kg/day for 14 days) showed little change although its activity in spermatozoa was dramatically decreased.     

Effects on rat testis of 1.95-GHz W-CDMA for IMT-2000 cellular phones

In recent years concern has arisen whether carrying a cellular phone near the reproductive organs such as the testes may cause dysfunction and particularly decrease in sperm development and production, and thus fertility in men. The present study was performed to investigate the effects of a 1.95 GHz electromagnetic field on testicular function in male Sprague-Dawley rats. Five week old animals were divided into 3 groups of 24 each and a 1.95-GHz wide-band code division multiple access (W-CDMA) signal, which is used for the freedom of mobile multimedia access (FOMA), was employed for whole body exposure for 5 hours per day, 7 days a week for 5 weeks (the period from the age of 5 to 10 weeks, corresponding to reproductive maturation in the rat). Whole-body average specific absorption rates (SAR) for individuals were designed to be 0.4 and 0.08 W/kg respectively. The control group received sham exposure. There were no differences in body weight gain or weights of the testis, epididymis, seminal vesicles, and prostate among the groups. The number of sperm in the testis and epididymis were not decreased in the electromagnetic field (EMF) exposed groups, and, in fact, the testicular sperm count was significantly increased with the 0.4 SAR. Abnormalities of sperm motility or morphology and the histological appearance of seminiferous tubules, including the stage of the spermatogenic cycle, were not observed. Thus, under the present exposure conditions, no testicular toxicity was evident.     

Effects on rat testis of 1.95-GHz W-CDMA for IMT-2000 cellular phones

In recent years concern has arisen whether carrying a cellular phone near the reproductive organs such as the testes may cause dysfunction and particularly decrease in sperm development and production, and thus fertility in men. The present study was performed to investigate the effects of a 1.95?GHz electromagnetic field on testicular function in male Sprague-Dawley rats. Five week old animals were divided into 3 groups of 24 each and a 1.95-GHz wide-band code division multiple access (W-CDMA) signal, which is used for the freedom of mobile multimedia access (FOMA), was employed for whole body exposure for 5 hours per day, 7 days a week for 5 weeks (the period from the age of 5 to 10 weeks, corresponding to reproductive maturation in the rat). Whole-body average specific absorption rates (SAR) for individuals were designed to be 0.4 and 0.08 W/kg respectively. The control group received sham exposure. There were no differences in body weight gain or weights of the testis, epididymis, seminal vesicles, and prostate among the groups. The number of sperm in the testis and epididymis were not decreased in the electromagnetic field (EMF) exposed groups, and, in fact, the testicular sperm count was significantly increased with the 0.4 SAR. Abnormalities of sperm motility or morphology and the histological appearance of seminiferous tubules, including the stage of the spermatogenic cycle, were not observed. Thus, under the present exposure conditions, no testicular toxicity was evident.     

吡哆素L-2-吡咯烷酮-5-羧酸酯雄性生殖毒性及机制研究

目的:研究吡哆素L-2-吡咯烷酮-5-羧酸酯(Metadoxine,MTDX)对雄性大鼠的生殖毒性及机制。方法:灌胃染毒雄性成年SD大鼠0,250,500和1000 mg/kgMTDX,每天1次,连续4周。染毒结束后观察性腺和附属性腺脏器系数、精子质量、组织形态学和血清睾酮等指标的变化。Hershberger方法检测MTDX抗雄激素活性作用:40只4周龄雄性SD大鼠行双侧睾丸切除手术,2周后,除1组皮下注射花生油并灌胃给予蒸馏水外,其余3组去势大鼠每天皮下注射丙酸睾酮(TP,1 mg/kg),并同时灌胃给予蒸馏水或MTDX(500,1000 mg/kg),连续7 d,观察雄激素依赖组织重量的变化。对体外培养睾丸碎块合成睾酮的影响:利用离体组织培养和放射免疫技术,观察不同浓度MTDX对体外培养睾丸碎块合成睾酮的影响。结果:1000 mg/kg剂量组大鼠睾丸、附睾、前列腺和精囊腺脏器系数明显降低;精子数量和精子存活率减少,精子活力降低,精子畸形率增高,血清T无变化;500 mg/kg剂量组在睾丸相对重量、精子数量和精子活力方面与对照组比较有显著性差异。在Hershberger实验中,1000 mg/kg组大鼠的精囊腺、前列腺以及球海绵体肌的脏器系数值均显著低于对照组。MTDX各剂量组睾丸培养液中睾酮的含量与对照组相比均没有显著性差异。结论:MTDX能引起雄性大鼠生殖毒性,这种毒性作用可能与其具有抗雄激素样作用有关。     

三氧化二砷亚急性染毒对雄性小鼠生殖与免疫毒性的研究

目的探讨As2O3亚急性染毒对雄性小鼠生殖与免疫毒性作用。方法24只清洁级KM雄性小鼠,分为对照组、低、中及高剂量染砷组。分别给予去离子水,As2.0、4.0、8.0mg/kg体重灌胃染毒7天。实验结束后剖杀动物取睾丸、附睾称重、计算器官指数并测定附睾精子数,摘取免疫器官胸腺、脾脏称重、计算免疫器官指数。结果(1)高剂量组睾丸及附睾重量低于正常对照组(P<0.05),但各组睾丸指数与对照组没有差异;各染砷组精子数均低于对照组(P>0.05),且中、高剂量组精子畸形率上升显著(P<0.05);(2)中、高剂量组免疫器官重量及指数降低,且高剂量组脾脏重量及指数显著低于对照组(P<0.05)。结论As2O3可致小鼠某些生殖和免疫毒性指标改变。     

Antifertility effects of 6-chloro-6-deoxyglucose in the male rat

Male rats were treated with daily oral doses of 12, 24, or 48 mg/kg of 6-chloro-6-deoxy-glucose (6CDG) or with 5 mg/kg of α-chlorohydrin for 28 days. Continuous fertility trials were conducted throughout the dosing period and for 3 weeks following dosing. 12 mg/kg/day of 6CDG produced partial infertility, while 24 and 48 mg produced almost complete infertility after 7 days of dosing. Although the males continued to mate with female rats after this time, only 4 to 20% of mated females became pregnant. In addition, those females which did become pregnant carried a significantly decreased number of fetuses at sacrifice one week after the breeding period. Males dosed with 5 mg/kg/day of α-chlorohydrin showed a gradual decrease in fertility over the four-week dosing period with a significant decrease in fetal numbers observed following one week of dosing. Recovery of normal fertility was achieved after one week withdrawal from all doses of 6CDG or from α-chlorohydrin. The ATP content of spermatozoa obtained from the treated rats and measured following an $\text{in vitro}$ incubation was significantly lower than controls for all groups at 4 weeks of dosing. However, 3 weeks following cessation of treatment, ATP had returned to control levels. The action of 6CDG is rapid in onset and associated with no effect on testis or accessory organ weight. These observations, together with the suppression of intracellular levels of ATP in epididymal spermatozoa, are consistent with an epididymal site of action of this compound or metabolites mediated through the glycolytic pathway.     

敌敌畏、乐果和马拉硫磷混合染毒对雄性小鼠生殖功能的影响

目的 研究敌敌畏、乐果和马拉硫磷混合染毒后对雄性小鼠生殖功能影响的特点和可能机制。方法 将105只雄性ICR小鼠按体重分层随机分成7组,每组15只,即对照组(0 mg/kg),敌敌畏、乐果和马拉硫磷混合低( 10.8 mg/kg)、中(21.5mg/kg)、高剂量组(43.0 mg/kg),以及敌敌畏组(5.1 mg/kg)、乐果组(12.6 mg/kg)和马拉硫磷组(25.3 mg/kg),经口连续灌胃染毒35 d,每天1次。染毒第36天后处死动物。测量小鼠体重、精子活力,观察精子数量及精子畸形率,检测血清中性激素[包括睾酮(T)、卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)等]的水平,并观察睾丸及附睾的病理及电镜下改变。结果 染毒后第14天,混合高剂量组小鼠体重[(22.40±3.07)g]低于对照组[(26.73±2.82)g](P＜0.05);染毒后第28天,混合中剂量组小鼠体重[(30.00±4.93)g]亦低于对照组[(33.13±3.29)g](P ＜0.05)。混合中、高剂量组精子数[分别为(321.17±18.19)×106/g附睾重、(225.00±19.67)×106/g附睾重]和精子活力[分别为(64.67±9.91)％、(57.83±9.66)％]均低于对照组[分别为( 373.33±14.65)× 106/g附睾重、(75.17±7.68)％](P值均＜0.05);精子畸形率[分别为(43.33 ±8.66)‰、(55.00±13.80)‰]高于对照组[(32.67±8.17)‰]（P值均＜0.05）;与对照组相比[FSH、E2、LH、T分别为(1.41±0.20)、(17.32±2.72)、(8.75±1.32)、（3.45±0.80）nmol/L],混合中、高剂量组小鼠血清中FSH[分别为(3.14±0.62)、(3.85±0.37) nmol/L]、E2[分别为(36.81±6.68)、（43.76±9.82）nmol/L]水平升高（P值均＜0.01）,LH[分别为(5.21 ±1.23)、(4.27±1.09) nmol/L]、T[分别为(1.37±0.38)、(0.73±0.18)nmol/L]水平降低（P值均＜0.01）。混合高剂量组小鼠睾丸成熟精子数减少,并可见结构异常的精子头、精子尾。结论 敌敌畏、乐果和马拉硫磷混合联合染毒可直接损害小鼠睾丸及附睾的结构和功能,而导致生殖细胞生成过程异常;并导致下丘脑-垂体-性腺轴性激素的分泌紊乱。     

Cadmium absorption and retention by rats fed durum wheat (Triticum turgidum L. var. durum) grain

A whole-body radioassay procedure was used to assess the retention and apparent absorption by rats of Cd in kernels of durum wheat (Triticum turgidum L. var. durum) harvested from plants grown hydroponically in 109Cd-labelled nutrient solution. Wholegrain wheat, containing 5 micromol Cd (570 microg)/kg dry weight labelled intrinsically with 109Cd, was incorporated into test meals fed to rats that had been maintained on diets containing marginally adequate, adequate or surplus levels of Zn (0.12 mmol (8 mg), 0.43 mmol (28 mg) or 1.55 mmol (101 mg) Zn/kg respectively), and either 0 or 50 g durum wheat/kg. Regardless of diet, all rats consumed about 99 % of the test meal offered. In rats fed diets without wheat, initial Cd absorption averaged 7.7, 4.6 and 2.4 % of the dose when the diet contained 0.12 mmol (8 mg), 0.43 mmol (28 mg) or 1.55 mmol (101 mg) Zn/kg diet respectively. In rats fed wheat-containing diets, initial Cd absorption averaged 3.8 and 2.6 % of the dose when dietary Zn concentration was 0.12 mmol (8 mg) and 0.43 mmol (28 mg)/kg diet respectively. The amount of Cd retained in the body at 15 d postprandial was <2 % of the dose in all rats, and decreased as Zn in the diet increased. Even at 15 d postprandial, 32 to 44 % of the Cd retained in the body was still in the gastrointestinal tract. The results show that: (1) the bioavailability to rats of Cd in wholegrain durum wheat was depressed when wholegrain wheat was part of the regular diet; (2) increased intake of dietary Zn lowered Cd absorption and retention; (3) retention of Cd in the body at 15 d postprandial from diets containing adequate Zn was <1.3 %.     

Antifertility effects of PGE2 and PGF2alpha

The effectiveness of prostaglandins to modify egg transport, to stimulate uterine contractility and to induce luteolysis suggested their possible role as postcoital contraceptives. PGE₂ and PGF_2α were injected at 24 $\text{hours postcoitum (h p.c.)}$ or at 4 $\text{days postcoitum (d p.c.)}$ in rabbits. Effects on fertility were studied at autopsy 14 $\text{d p.c.}$ When PGE₂ was injected 24 $\text{h p.c.}$, 25% of the eggs failed to implant and 11% of the embryos were degenerating. The injection of PGF_2α at 24 $\text{h p.c.}$ inhibited the implantation of 61% of the eggs and 17% of the embryos were degenerating. Local injection of PGE₂ at 4 $\text{d p.c.}$ succeeded in inhibiting implantation in 95% of the eggs while 77% of the eggs failed to implant following local injection of PGF_2α at 4 $\text{d p.c.}$ Intravenous injection of PGE₂ and PGF_2α at 4 $\text{d p.c.}$ failed to disturb implantation.     

Antifertility activity and general pharmacological properties of ORF 13811: A synthetic analog of zoapatanol

ORF 13811, a synthetic analog of zoapatanol, was evaluated in a variety of $\text{in}$$\text{vivo}$ and $\text{in}$$\text{vitro}$ biological test systems to determine antifertility and uterotonic activity as well as its general pharmacological profile. ORF 13811 is a potent antifertility agent after oral administration in a number of animal species including mice, rats, guinea pigs, dogs and baboons. The single oral ED₅₀ for contragestational activity in the pregnant guinea pig (day 22), mouse (day 16) and rat (day 16) is in the range of 6 to 10 mg/kg. In pregnant beagle dogs, a dose-related contragestational effect was obtained witnin several days after oral administration of ORF 13811 in the dosage range of 10 to 30 mg/kg. ORF 13811, when administered to pregnant baboons, caused dose-related vaginal bleeding and evacuation of uterine contents within 3 days following treatment witn oral doses of 40 to 60 mg/kg. Serum progesterone levels were decreased in baboons and the degree of reduction correlated with contragestational activity. ORF 13811 was also effective in inhibiting implantation in mice, rats and hamsters, but required higher dose levels than those of the post-implantive treatments. $\text{In}$$\text{vitro}$ uterotonic properties of ORF 13811 were demonstrated by its ability to induce contraction of uterine strips obtained from female guinea pigs at two different reproductive stages (day 15 of the estrous cycle and day 22 of pregnancy). In these preparations ORF 13811 was approximately $\text{1}\text{30}$ to $\text{1}\text{50}\text{th}$ as potent as PGF₂α. In a series of pharmacological tests, ORF 13811 was found to possess slight sedative properties but was devoid of activity on pulmonary, gastrointestinal, and immune systems as well as in a number of biochemical tests, data not reported here. However, in cardiovascular studies, ORF 13811 appears to possess a vasoconstrictor profile in the dog, monkey and baboon as indicated by an increase in mean arterial blood pressure as well as total peripheral and regional vascular resistances. The $\text{in}$$\text{vitro}$ pharmacological profile of ORF 13811 was examined in myocardial tissue and vascular smooth muscle test systems and compared to PGF₂α. ORF 13811 was found to contract rat aortic strips, 15 times less potent than PGF₂α. The compound had no direct effect on isolated guinea pig atria or papillary muscle. In summary, ORF 13811 is a potent orally active antifertility agent characterized primarily as a contractor of uterine and vascular smooth muscle.     

环境雌激素壬基酚对小鼠生精功能的影响

目的　研究经口染毒壬基酚 (NP)对小鼠生精功能的影响及可能的机制。方法　选健康性成熟雄性昆明种小鼠连续灌胃NP 5d ,剂量为 1 0 0 ,2 0 0 ,4 0 0mg/kg。于首次染毒后第 1 4天和第 35天随机分批各处死 5只小鼠 ,称量睾丸、附睾及精囊腺重量并计算脏器系数。检测第 1 4天处死的小鼠初级精母细胞染色体畸变率 ,第 35天处死小鼠检测精子数、活精率、活动度和畸形发生率。结果　染毒NP剂量达 2 0 0 ,4 0 0mg/kg时精子数明显减少 ,不动精子数、精子畸形率、初级精母细胞染色体畸变率明显升高 ,活精率仅在 4 0 0mg/kg组明显降低 ,与阴性对照组比较 ,差异均有显著性 (P <0 0 5 ) ,并均呈明确的剂量 -反应关系 (P <0 0 5 )。结论　经口染毒NP可损伤小鼠的生精功能 ,NP直接损伤生精细胞和初级精母细胞染色体 ,是产生上述结果的机制之一     

The reversible antifertility effect of Piper betle Linn. on Swiss albino male mice

To study the antifertility effect of an extract (alcoholic) of the leaf-stalk of Piper betle Linn., one set of experiments with two different doses in Swiss male albino mice were evaluated. Initially, 500 mg of the leaf-stalk extractive for 30 days and then 1000 mg for next 30 days/animal/day/kg body weight were administered orally. The extract reduced fertility to 0% within 60 days. Suppression of cauda epididymal sperm count and motility (p <0.05) was observed. Biochemical parameters did not show any marked alterations in testosterone content in serum nor 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity in testes although fructose content in seminal vesicles was reduced as are the weights of reproductive organs. The cholesterol content in testes increased, although not appreciably. After cessation of drug (plant extract) treatment, the altered parameters recovered. Results suggest that the contraceptive effect of the extract of leaf-stalk of Piper betle Linn. is mainly on the maturation process of spermatozoa in epididymides without influencing hystemic hormonal profiles. Withdrawal of the extract restored all altered parameters including organ weights and fertility after 60 days.