Age-specific effect of phthalate ester on testicular development in rats

Purpose

Phthalate esters have been shown to induce testicular damage in both adult and immature rats; however, there have been, so far, few reports describing the age-specific effects of phthalate esters on testicular function. The aim of this study is therefore to investigate the age-specific effects of mono-n-butyl phthalate (MBP) on the testes in both prepubertal and mature adult rats.

Materials and methods

Both prepubertal male rats and adult mature male rats were fed special rat chow containing 1% MBP for 10 days. Control prepubertal and adult rats were fed standard commercial rat chow during the same period as the MBP-treated rats. After 10 days of feeding, all rats were killed, and the testes were removed. The weight of the testis was measured, and histological examination of the testis was performed. In addition, the frequency of an apoptotic cell appearance in the seminiferous tubules was determined in both MBP-treated and control groups.

Results

In the prepubertal rats, the mean weight of the testes was significantly lower in the MBP-treated rats than in the control rats. A histological examination of the MBP-treated testes showed a decreased seminiferous tubular diameter and an inhibited maturation of germ cells in comparison to those of the control testes. Furthermore, apoptotic cells appeared more frequently in the MBP-treated testes than in the control testes. Although in adult mature rats, no significant difference was observed in either the testicular weight or the histological findings between the MBP-treated and control rats.

Conclusions

The oral administration of MBP to male rats was observed to produce more pronounced testicular damage in prepubertal rats than in adult mature rats. Immature testes may thus be more sensitive to MBP, which induces the germ cell apoptosis in seminiferous tubules and testicular atrophy in prepubertal young rats.     

邻苯酸二甲酯（塑化剂）对大鼠肾脏及生殖系统的影响

目的探索邻苯酸二甲酯（塑化剂）对大鼠肾脏及生殖系统的影响。 方法Wistar清洁级雄性大鼠60只,随机数字表法分为低剂量组、中剂量组、高剂量组和对照组,每组15只,用药组分别给予剂量100、500、1 000 mg/（kg·d）的邻苯酸二甲酯,对照组仅给予植物油。6周后检测血清肌酐（Cr）、尿素氮（BUN）、黄体生成素（LH）、卵泡刺激素（FSH）、睾酮（T）、胱抑素C（Cys-C）,β2-微球蛋白（β-Mg）水平。HE染色观察肾脏组织形态学变化。组间比较采用单因素方差分析。 结果高剂量组Cr、BUN明显升高（F=11.70,4.16;P<0.05）,而Cys-C、β2-微球蛋白在低、中、高剂量组均明显升高（F=31.16,8.05;P<0.05）。高剂量组中血清睾酮水平降低;低剂量组LH水平升高,而中剂量组、高剂量组血清LH水平降低;低、中、高剂量组血清FSH水平升高（F=4.82,59.34,6.91;P<0.05）。对照组和低剂量组大鼠肾脏组织结构未见明显改变;中剂量组大鼠肾脏中肾小球出现萎缩,高剂量组大鼠肾小球出现萎缩,变性,坏死。 结论邻苯酸二甲酯可引起大鼠生殖内分泌激素水平的变化和肾小球病变。     

Effects of smoking on testicular function and fertilizing potential in rats

We evaluated the effects of smoking on testicular function and fertilizing potential in rats. Twenty rats (group A) were exposed to the smoke of 20 cigarettes for 1 h per day. Ten rats (group B) were exposed to the smoke of 40 incense sticks for 1 h per day, and an additional 10 rats served as a control group (group C). After 10 weeks of daily exposure, serum levels of nicotine and cotinine were assessed, and a mating test was conducted. Five days later, serum concentrations of testosterone before and after human chorionic gonadotropin (hCG) stimulation, gonadotropins, and epididymal sperm content and motility were evaluated. In addition, in vitro fertilization was carried out. Nicotine and cotinine were detected in group A, but not in groups B and C. Basal serum testosterone and gonadotropin concentrations did not differ significantly among the three groups, but the testosterone response to hCG stimulation was significantly lower in group A than in groups B and C. Group A showed significant reductions in epididymal sperm content and motility, and in fertility in vivo and in vitro. These findings suggest that smoking leads to a secretory dysfunction of the Leydig cells, and also a deficiency in sperm maturation and spermatogenesis. In addition, smoking has a detrimental effect on sperm fertilizing potentials in vivo and in vitro. Received: 18 December / Accepted: 27 May 1997     

Time-specific effects of mono-n-butyl phthalate on the transabdominal descent of the testis in rat fetuses

OBJECTIVE: To determine the time-specific effects of mono-n-butyl phthalate (MBP) on the transabdominal migration of the testis in fetal rats. Materials and methods Three groups of pregnant rats were administered MBP by stomach-tube feeding when the fetus was at 7-10 days of gestation in group 1, 11-14 days in group 2, and 15-18 days in group 3; controls (group 4) were given vehicle only from 7-18 days. At 20 days of gestation the fetuses were obtained by Caesarean section, and the position of the testes, the development of the gubernaculum, cranial suspensory ligament and the epididymis were examined. RESULTS: The timed intervals of MBP administration showed that the maximum inhibition of transabdominal testicular descent was at 15-18 days of gestation. There was an elongated gubernaculum and hypertrophic cranial suspensory ligament in the MBP-treated rat fetuses. Furthermore, the epididymis showed a few small ducti deferentia, although there were no remarkable changes in either the Sertoli and Leydig cells in these testes. The mean (SEM) content of testicular testosterone was significantly less (P < 0.001) in the MBP-treated rats, at 50.9 (3.8) pg/testis, than in the controls, at 676 (33.3) pg/testis. CONCLUSIONS: These findings indicate that a brief exposure to MBP during fetal development can inhibit the transabdominal migration of the testis and reduce testosterone content in rats, although the relationship between migration and the testicular testosterone content remains unknown.     

Effects of pre- and postnatal cysteamine exposure on renal function in the rat

The safety of cysteamine after renal transplantation and during pregnancy is an important issue, since girls with cystinosis are in better health on cysteamine therapy and thus more likely to become pregnant. In the first study, cysteamine was given to pregnant rats on days 6.5–18.5 post conception in oral doses of 0, 37.5, 75, 100, and 150 mg/kg per day. The dams were sacrificed on day 20.5, the fetal kidneys removed and prepared for histological examination. In the second study, cysteamine was given to dams on days 6.5–19.5 post conception in oral doses of 0, 37.5, 50, and 75 mg/kg per day. Dams were allowed to give birth naturally and pups were given cysteamine on days 4–21 to yield the same oral doses of cysteamine given to the dam. Renal function was evaluated on day 35. Histological examination of fetal kidneys revealed no changes even in kidneys from fetuses with growth retardation and malformations. Furthermore, there were no alterations in renal function in offspring on day 35. These findings demonstrate that cysteamine therapy does not affect renal development in the rat. Further investigations will be required to prove whether cysteamine therapy has the potential to affect renal development in the human. Received: 25 September 1998 / Revised: 17 November 1998 / Accepted: 13 December 1998     

邻苯二甲酸二丁酯致尿道下裂大鼠发育异常和阴茎病理学改变研究

目的邻苯二甲酸二丁酯（DBP）孕晚期染毒诱导子代雄鼠尿道下裂发生和探讨DBP致尿道下裂雄鼠发育异常和阴茎病理学改变。方法雌鼠怀孕14～18d，每天分别灌胃给予大豆油（A组），DBP500（B组）、800（C组）、1200（D组）mg／kg体重，分娩后统计仔鼠数和雄仔鼠体重。出生后（PND）7d测量雄仔鼠肛门生殖器距离（AGD），观察尿道下裂发生率和尿道下裂阴茎病理学改变。PND70,对尿道下裂雄仔鼠称重后解剖，评价发育情况。结果C组仔鼠数和雄仔鼠体重明显减少；D组出现孕鼠死亡和零产仔；尿道下裂仅C组发生。发生率为36．5％。PND7，B、C组雄仔鼠AGD和A组相比明显减小。阴茎连续性病理切片显示典型尿道下裂改变。解剖得尿道下裂雄仔鼠肝、肾、前列腺、睾丸、附睾脏器系数与A组相比明显减小，脑垂体脏器系数明显增大。结论800mg／kg体重DBP孕晚期染毒能高诱导雄仔鼠尿道下裂发生，DBP不仅损害雄仔鼠生殖系统，还引起发育异常。     

Biphasic effects of postnatal exposure to diethylhexylphthalate on the timing of puberty in male rats

Phthalate esters such as di(2-ethylhexyl)phthalate (DEHP), which are commonly found in cosmetics and in flexible plastics distributed by the food, construction, and medical products industries, have been classified as anti-androgens. High-dose DEHP exposure in utero is associated with decreased androgen levels. However, when administered after birth, low doses of DEHP (eg, 10 mg/kg body weight) may stimulate androgen production. In the present study, the potential of phthalate exposure to advance or delay the timing of puberty was assessed. Male Long-Evans rat pups were chronically subjected to low or high doses of DEHP, with the androgen-driven process of preputial separation serving as an index of pubertal timing. Rats were treated with 0, 10, 500, or 750 mg/kg body weight DEHP for 28 days starting at day 21 postpartum. The average age at which the animals completed preputial separation was measured in each group. The age of preputial separation was 41.5 +/- 0.1 days postpartum in controls (vehicle). The 10 mg/kg DEHP dose advanced pubertal onset significantly to 39.7 +/- 0.1 days postpartum, whereas the 750 mg/kg DEHP dose delayed pubertal onset to 46.3 +/- 0.1 days postpartum. The 10 mg/kg DEHP dose also significantly increased serum testosterone (T) levels (3.13 +/- 0.37 ng/mL) and seminal vesicle weights (0.33 +/- 0.02 g) compared with control serum T (1.98 +/- 0.20 ng/mL) and seminal vesicle weight (0.26 +/- 0.02 g), while the 750 mg/kg dose decreased serum T (1.18 +/- 0.18 ng/mL) as well as testes and body weights. Direct action of the DEHP metabolite, monoethylhexylphthalate (MEHP), on Leydig cell steroidogenic capacity was investigated in vitro. MEHP treatment at a low concentration (100 microM) increased luteinizing hormone-stimulated T production, whereas 10 mM concentrations were inhibitory. In conclusion, data from the present study indicate that DEHP has a biphasic effect on Leydig cell function, with low-dose exposure advancing the onset of puberty. High doses of DEHP, which are anti-androgenic, may also be outside the range of real environmental exposure levels.     

Long-term effects of in utero exposure to cyclosporin A on renal function in the rabbit

The number of pregnant women who receive cyclosporin A (CsA) after transplantation or for autoimmune disease has increased. CsA and its metabolites can cross the placental barrier and thus interfere with fetal development. It was shown previously that rabbits that were exposed in utero to 10 mg/kg per d CsA from the 14th to the 18th day of gestation presented a 25% nephron reduction. Thus, this study was conducted to assess the long-term systemic and renal effects of a CsA-induced nephron reduction. Twenty-two pregnant New Zealand white rabbits were randomly divided into two groups: Twelve received 10 mg/kg per d CsA from day 14 to day 18 of gestation, and 10 were used as controls. Rabbits that were born to these animals were evaluated at 4, 11, 18, and 35 wk of life. Pups that were exposed antenatally to CsA presented first a permanent nephron deficit; second, glomerular, tubular, and intrarenal hemodynamics dysfunction; third, enlarged kidneys with numerous tubular and glomerular lesions; and, fourth, an endothelin-dependent systemic hypertension that worsened with age. In utero exposure to CsA induced a nephron reduction that led to systemic hypertension and progressive chronic renal insufficiency in adulthood. A long-term clinical survey is mandatory in infants who are born to mothers who were treated with cyclosporin during pregnancy.     

不同类型疝补片对大鼠生殖功能的影响

目的建立大鼠腹股沟疝实验模型,对比不同类型的疝修补网片对大鼠生殖功能的影响。方法选取30只成年雄性SD大鼠,(8.5±0.3)周,体质量(230±35)g。随机分成5组,每组6只。正常对照组(NC组)、假手术组(SO组)、轻型聚丙烯补片组(LWPP组)、重型聚丙烯补片组(HWPP组)和复合补片组(CM组)。NC组仅给予腹腔麻醉后下腹部脱毛处理,SO组仅分离右侧腹股沟区输精管后逐层缝合切口,而后3组分别实施右侧腹股沟区手术分离输精管,而后用各自相对应补片包绕输精管。术后3个月采集标本并制作病理切片,观察补片对大鼠睾丸、精子和输精管的影响。结果CM组与周围组织及精索轻度粘连,对睾丸输精管损伤较小,生殖细胞质量下降不明显。LWPP和HWPP组与周围组织粘连较重,对睾丸输精管损伤严重,生殖细胞质量下降明显,生殖功能受到影响,材质相同的聚丙烯补片中,LWPP的影响程度明显小于HWPP。5组精子活率、a+b级精子、摆动性、线性度、前向性及直线运动精子活率比较,差异均有统计学意义(P均<0.05)。SO组、CM组、LWPP组及HWPP组精子活率及a+b级精子与NC组比较,差异均有统计学意义(P均<0.05);LWPP组及HWPP组精子活率及a+b级精子与SO组比较,差异均有统计学意义(P均<0.05);LWPP组与HWPP组精子活率及a+b级精子比较,差异有统计学意义(P<0.05)。5组大鼠精子总数比较,差异无统计学意义(P>0.05);5组大鼠精子密度、直线速度、曲线速度及鞭打频率比较,差异有统计学意义(P<0.05)。SO组、CM组、LWPP组及HWPP组精子密度与NC组比较,差异均有统计学意义(P均<0.05);LWPP组及HWPP组精子密度与SO组比较,差异均有统计学意义(P均<0.05);LWPP组与HWPP组精子密度比较,差异有统计学意义(P<0.05)。5组大鼠输精管管壁变化分级评分比较,差异有统计学意义(P<0.05);术后3个月5组大鼠输精管腔内皱襞个数比较,差异有统计学意义(P<0.05)。结论不同类型的疝补片对雄性大鼠生殖功能的影响不同,轻量型大网孔补片对生殖功能造成的影响比重量型小网孔补片造成的影响小。CM组较LWPP组和HWPP组对生殖功能的影响小,造成的损伤轻。建议对需行腹股沟疝修补手术且有生育要求者,在有条件的前提下可推荐使用复合补片。     

肥胖对男性生殖功能影响的研究进展

近年来肥胖症的发病率不断上升,而在肥胖诸多的并发症中,其对男性生育力的影响已受到广泛关注。研究表明,肥胖常导致男性精液质量下降、精子蛋白质组学变异、勃起功能障碍等,从而使男性生育力低下,最终可能导致不育。肥胖引起男性不育症的机制较为复杂且不甚明确,物理因素、神经-内分泌因素、遗传因素等均可能参与其中,还需对此方面内容做进一步的深入研究。本文综述了上述相关因素对肥胖男性生殖功能的影响机制及具体表现,旨在积极防控男性因肥胖造成的生育力低下、保障人群生殖健康。     

低剂量纳米氧化镍亚慢性染毒对雄性大鼠生殖功能及子代的影响

目的:研究低剂量纳米氧化镍亚慢性染毒对雄性大鼠生殖功能及雌性大鼠胚胎发育的影响。方法:将50只健康雄性SD大鼠(180～220 g)按体重采用随机数字表随机分为5组,每组10只,分别为生理盐水对照组(阴性对照组)、微米氧化镍组(4.0 mg/ml,阳性对照组)及纳米氧化镍低、中、高剂量组(浓度分别为0.16、0.8、4.0 mg/ml);以非暴露式气管滴注法染毒,1次/3d,60 d后与正常成年雌性大鼠按1∶2合笼。确定雌鼠怀孕后,处死雄鼠,称量雄性大鼠体重、睾丸、附睾,计算脏器系数;检测附睾精子浓度及活精子率,采用原子荧光谱法测定血液和精液镍含量;于妊娠第20天处死雌鼠,观察雌雄交配受孕情况、受精卵着床数、活胎数、死胎数及吸收胎数。结果:染毒60 d后,与阴性对照组和微米氧化镍阳性对照组相比,各剂量纳米氧化镍组大鼠体重,睾丸、附睾重量及其脏器系数均无显著差异。与阴性对照组相比,中、高剂量纳米氧化镍组大鼠精子浓度[(7.49±1.46)、(6.30±1.36)×10~6/ml vs(9.36±0.98)×10~6/ml,P0.05]和活精子率[(68.26±16.63)%、(65.88±14.68)%vs(85.35±9.16)%,P0.05]显著下降,畸形精子率显著升高[(13.99±4.87)%、(15.38±8.86)%vs(8.30±2.47)%,P0.05];与阴性对照组相比,中、高剂量纳米氧化镍组孕鼠的吸收、死胎率显著增高(6.89%、7.37%vs 1.18%,P0.05);与阴性对照组相比,中、高剂量纳米氧化镍组大鼠血液镍[(0.52±0.34)、(0.82±0.44) mg/L vs(0.13±0.16) mg/L,P0.05]和精液镍[(0.35±0.23)、(0.63±0.61) mg/L vs(0.08±0.13) mg/L,P0.05]显著升高;相关性分析结果显示,血液镍和精液镍含量显著相关(r=0.912,P0.01),精液镍含量与活精子率呈负相关(r=-0.879,P0.01),而与畸形精子率呈正相关(r=0.898,P0.01)。结论:0.16 mg/ml纳米氧化镍染毒对大鼠生殖功能未见明显的毒性作用,0.8、4.0 mg/L纳米氧化镍染毒60 d可对雄性大鼠产生生殖毒性,并对胚胎有一定的致畸作用。     

邻苯二甲酸二丁酯对青春期大鼠雄性生殖系统的影响

目的:探讨邻苯二甲酸二丁酯(DBP)对青春期大鼠雄性生殖系统的影响。方法:5周龄雄性SD大鼠用DBP灌胃染毒30d,染毒剂量包括:10、100、500mg/(kg.d),对照组仅给予溶剂(玉米油)。染毒结束后,检测睾丸、附睾、垂体、肝脏重量及脏器系数。苏木精-伊红(HE)染色法检测睾丸、附睾组织病理改变。放免法测定血清中黄体生成素(LH)、卵泡刺激素(FSH)、睾酮(T)水平。实时定量反转录PCR测定类固醇激素合成急性期调节蛋白(StAR)、增殖细胞核抗原(PCNA)、细胞色素P450胆固醇侧链裂解酶(P450scc)、清道夫受体(SR)mRNA的相对表达变化。结果:500mg/(kg.d)组中,睾丸及附睾重量明显减轻,垂体、肝脏的重量没有明显改变。100mg/(kg.d)和500mg/(kg.d)DBP导致了睾丸组织病理学改变。500mg/(kg.d)DBP组中血清T、LH水平降低,血清FSH升高。10mg/(kg.d)DBP组血清LH及FSH水平升高。500mg/(kg.d)DBP抑制了StAR、PCNAmRNA的表达。10mg/(kg.d)DBP提高了P450sccmRNA的表达水平,SRmRNA表达水平没有明显改变。结论:高剂量DBP对雄性生殖系统有明显毒性效应,较低水平的DBP改变了血清中促性腺激素LH的水平,并有可能以此来改变睾丸中P450sccmRNA的表达。     

L-Arginine effects on blood pressure and renal function of intrauterine restricted rats

We have previously demonstrated that 3-month-old rats submitted to 50% intrauterine food restriction showed a decreased number of nephrons with increased glomerular diameter, a fact that suggests compensatory hypertrophy. In the present study, we extended the investigation and performed serial blood pressure measurements and renal function evaluation in 8- and 12-week-old rats submitted to 50% intrauterine food restriction (groups R8 and R12) and in age-matched control rats (groups C8 and C12). After weaning, six to eight animals from each group received oral supplements of 2% L-arginine ( L-arg) solution for 4 or 8 weeks (groups CA8, CA12, RA8, RA12). Our findings showed that mean blood pressure (MBP), which was significantly increased from 8 weeks on in R rats, markedly decreased after L-arg supplementation. In control animals, no alterations in MBP were observed with L-arg. Proteinuria was within normal limits in all groups studied but L-arg caused a significant decrease in this parameter in both the RA8 and RA12 groups. Glomerular filtration rate (GFR, ml/min per kg) was significantly decreased in the C8 control group (3.75+/-0.12) and in both restricted groups R8 and R12, (2.47+/-0.13 and 3.76+/-0.16, respectively) compared with the C12 group (6.09+/-0.31; P<0.05 for all comparisons). L-Arg caused an increase in GFR only in the younger groups, C8 and R8. In a separate set of experiments, acetylcholine (ACh)-induced relaxation was examined in mesenteric arteries. The R12 group showed a significant impairment of the response to ACh, which returned to normal values after L-arg supplementation. Urinary excretion of NO(x) (NO3- + NO2-) was significantly decreased in 8- and 12-week-old food-restricted rats relative to control rats. Our data indicate that, besides the known decrease in absolute nephron number, disturbances in the production/sensitivity to the L-arg-nitric oxide system may contribute to the early appearance of hypertension in the offspring of mothers submitted to significant food restriction.     

Gestational exposure to atrazine: effects on the postnatal development of male offspring

Atrazine is an herbicide used worldwide to control grasses and weeds. Previous studies have shown that, depending on atrazine's administered dose, exposure of male rats during the early postnatal or peripubertal periods can result in alterations in endocrine function. The gestational period is particularly vulnerable to environmental agents; however, the possible effects of atrazine exposure during this period have received only limited attention. Herein we examine the dose effects of atrazine exposure during Sprague-Dawley rat gestation on the postnatal development of male offspring. Pregnant dams were treated by oral gavage with atrazine at 0 to 100 mg/kg/d from gestational day 14 to parturition. Thereafter, neither the pups nor the dams received atrazine. Atrazine had no effect on the number of live births per dam. Neonatal pup survival was affected, however, with increased pup death seen at doses of 10 mg/kg/d and higher. There was no effect of atrazine on the testosterone concentration within the testes of newborn pups. Anogenital distance, an androgen-dependent process, decreased from the control level at the 75 and 100 mg/kg/d doses, with the decrease reaching significance at 100 mg/kg/d. Preputial separation, also an androgen-dependent process, was delayed significantly compared with that in controls in response to the 50 and 100 mg/kg/d doses. At postnatal day 60, serum testosterone concentrations were reduced significantly from controls in the 50 to 100 mg/kg/d groups. However, these decreases had little effect on seminal vesicle or ventral prostate weights. These results, taken together, are suggestive of antiandrogenic effects of gestational atrazine exposure on male offspring, although for most parameters, the doses used in this study are unlikely to be experienced under any but experimental conditions.     

Evaluation of male-mediated reproductive toxic effects of methamidophos in the mouse

The reproductive toxicity of the insecticide methamidophos was studied in male mice. Adult male mice were treated by gavage with methamidophos at doses of 0, 1, 2 and 3 mg kg(-1) day(-1) for 4 weeks before mating with untreated females. Brain and skeletal muscle acetylcholinesterase activity was inhibited in the middle- and high-treated groups. Methamidophos treatment was associated with a decreased number of live foetuses and an increased number of dead and resorption foetuses at 2 and 3 mg kg(-1) day(-1) treated groups. The per cent morphologically normal spermatozoa were affected in the 2 and 3 mg kg(-1) day(-1) dose groups; however, sperm motility and count were decreased in the same treated groups compared to the control. Histological examination of brain, muscles, testes and epididymis revealed histological abnormalities in a dose-dependent manner. The current study demonstrated adverse effects of male methamidophos exposure on pregnancy outcome with effects on sperm parameters at 2 and 3 mg kg(-1) day(-1) .     

Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters

Certain Phthalate esters have been shown to produce reproductive toxicity in male rodents with an age dependent sensitivity in effects with foetal animals being more sensitive than neonates which are in turn more sensitive than pubertal and adult animals. While the testicular effects of phthalates in rats have been known for more than 30 years, recent attention has been focused on the ability of these agents to produce effects on reproductive development in male offspring after in utero exposure. These esters and in particular di-butyl, di-(2-ethylhexyl) and butyl benzyl phthalates have been shown to produce a syndrome of reproductive abnormalities characterized by malformations of the epididymis, vas deferens, seminal vesicles, prostate, external genitalia (hypospadias), cryptorchidism and testicular injury together with permanent changes (feminization) in the retention of nipples/areolae (sexually dimorphic structures in rodents) and demasculinization of the growth of the perineum resulting in a reduced anogenital distance (AGD). Critical to the induction of these effects is a marked reduction in foetal testicular testosterone production at the critical window for the development of the reproductive tract normally under androgen control. A second Leydig cell product, insl3, is also significantly down regulated and is likely responsible for the cryptorchidism commonly seen in these phthalate-treated animals. The testosterone decrease is mediated by changes in gene expression of a number of enzymes and transport proteins involved in normal testosterone biosynthesis and transport in the foetal Leydig cell. Alterations in the foetal seminiferous cords are also noted after in utero phthalate treatment with the induction of multinucleate gonocytes that contribute to lowered spermatocyte numbers in postnatal animals. The phthalate syndrome of effects on reproductive development has parallels with the reported human testicular dysgenesis syndrome, although no cause and effect relationship exists after exposure of humans to phthalate esters. However humans are exposed to and produce the critical phthalate metabolites that have been detected in blood of the general population, in children and also human amniotic fluid.     

胃袖状切除术对2型糖尿病大鼠肾功能的影响

目的 探讨胃袖状切除术对2型糖尿病大鼠肾功能的影响及其机制.方法 通过腹腔内注射链脲菌素诱导SD大鼠糖尿病模型,共有36只大鼠诱导成功.选取血糖水平居中的30只大鼠随机分成3组(血糖17.88～23.65 mmol/L,平均20.32 mmol/L):胃袖状切除组、假手术组及对照组,每组10只.术后检测大鼠一般情况、血脂、肌酐,取大鼠24 h尿液检测24 h尿微量清蛋白排泄率.行血、尿肌酐检测计算肾小球滤过率,实验结束取肾称重并对肾小球进行病理学检查,PAS染色观察肾小球系膜扩张情况,计算系膜扩张率.通过免疫组化技术检测肾小球足细胞突触极蛋白表达率,进一步明确胃袖状切除手术对糖尿病大鼠肾功能的影响的机制.检测数据的组间比较采用单因素方差分析,组间两两比较采用t检验.结果 胃袖状切除组大鼠术后死亡1只,另两组大鼠无死亡.胃袖状切除组大鼠肾小球滤过率[(8.44 ±2.10) ml·g-1·d-1]、24 h尿蛋白排泄率[(36.04±11.10) mg/d]、血脂[总胆固醇(1.66±0.23) mmol/L,甘油三酯(1.25±0.17)mmol/L]、肾脏质量[(1.61±0.06)g]、肾小球系膜扩张率[(6.14±1.50)％]和足细胞突触极蛋白表达率[(20.44±2.99)％]均优于假手术组[(15.05 ±3.01)ml·g-1·d-1、(57.01±11.34) mg/d、(2.15±0.29) mmol/L、(1.65±0.23) mmol/L、(1.93±0.07)g、(11.32±2.09)％、(10.34±1.43)％]和对照组[(14.79±2.38)ml·g-1·d-1、(62.71±16.46) mg/d、(2.23±0.21) mmol/L、(1.59±0.20) mmol/L、(1.91±0.06)g、(10.82±1.79)％、(11.13±2.43)％](t=0.781 ～5.025,P值均＜0.05).结论 胃袖状切除手术可明显改善2型糖尿病大鼠模型的肾功能,手术可能通过改善肾小球系膜扩张及保护肾小球足细胞来改善肾功能.     

长期吸入低浓度七氟烷对小鼠生殖功能的影响

目的 评价长期吸入低浓度七氛烷对小鼠生殖功能的影响.方法 ICR雄性小鼠加只,日龄60 d,体重20～25 g,随机分为4组(n=10):对照组(C组);S1-3组分别吸入0.003%、0.01%和0.03%七氟烷.每天2 h,每周连续5 d,持续8周后处死动物.取睾丸和附皋,测定精子活动率、精子数量、精子畸变率、睾丸组织总乳酸脱氢酶(LDH)及乳酸脱氢酶同工酶-X(LDH-X)的活性,并观察睾丸组织超微结构.结果 与C组比较,S3组精子活动率降低、畸变率升高、睾丸组织LDH-X活性降低(P<0.05),S1,2组各指标差异无统计学意义(P>0.05),仅S3组睾丸组织出现病理学改变.结论 长期吸入0.03%七氟烷可导致雄性小鼠生殖功能异常,而长期吸入≤0.01%七氟烷对生殖功能未见影响.     

血清睾酮雌二醇比值变化对精子缺陷及生育力的影响

目的 了解血清睾酮(T)/雌二醇(E2)比值变化对精子缺陷程度及男性生育能力的影响.方法对90例已婚育龄男性进行血清T、E2、卵泡刺激素(FSH)、黄体生成素(LH)、催乳素和精液参数、精子形态测定,计算血清T/E2和精子多重缺陷指数.根据血清T/E2分为≤10(1组)、＞10(2组)及＞20(3组)分别比较.结果 1、2、3组精子密度和精子活动力分别为(66.8±39.6)×106、(57.6±33.9)×106、(77.4±26.0)×106/ml和(46.6±16.4)%、(44.9±16.0)%、(53.9±14.4)%,3组间差异无统计学意义(P均＞0.05).1组头部缺陷精子为(81.4±9.4)%,明显高于3组的(74.0±10.7)%(t=2.482,P=0.016);1、2组颈部缺陷精子为(16.9±8.6)%和(12.7±9.8)%,均明显高于3组的(7.1±3.9)%(t=4.113、2.050,P=0.000、0.046);1、2、3组尾部缺陷精子分别为(22.6±14.6)%、(14.6±9.0)%和(6.5±5.7)%,组间差异有统计学意义(t=2.722、3.996、3.110,P=0.008、0.000、0.003).2组精子畸形指数(SDI)(1.4±0.3)明显高于1组(1.3±0.2,t=2.293,P=0.025);2、3组畸形精子指数(TZI)分别为1.6±0.3和1.6±0.2,明显高于1组的1.4±0.2(t=2.285、2.727,P=0.025、0.009).1、2、3组中配偶有生育或妊娠经历者分别为13、16、6例,组间差异无统计学意义(x2=3.285、0.854、0.199,P=0.070、0.355、0.655),但2、3组相对危险度分别为1组的2.4倍和1.8倍.1、2、3组中特发性不育病例分别为25、15、7例,组间差异均无统计学意义(x2=0.735、0.200、0.038,P=0.391、0.655、0.845),1组相对危险度分别为2、3组的1.5倍和1.3倍.相关性分析结果发现,血清T/E2与头、颈和尾部缺陷精子比率呈显著负相关(r=-0.209、-0.316、-0.335,P=0.048、0.002、0.001).结论血清T/E2与精子头、颈及尾部缺陷呈显著负相关,其下降与男性生育概率降低有关,但并不影响精子密度及活动力,表明男性体内维持较高比例的T/E2水平对于精子发生过程中的精子形成阶段及受精能力有重要意义.

Abstract：

Objective To study the effect of the serum testosterone/estradiol ratio (T/E2) alteration on sperm defect and fertility. Methods The testosterone, estradiol, FSH, LH, PRL,sperm parameters and sperm morphology of 90 men were analyzed and the T/E2 and multiple anomalies index (MAI) were calculated. The patients were divided into 3 groups; T/E2≤10 (Ⅰ), T/E2＞10 (Ⅱ), and T/E2＞20 (Ⅲ). Results The sperm concentration and motility among the 3 groups were not significantly different (P＞0. 05). The percentages of the sperm whose head, neck and tail were abnormal declined gradually with the increase of the T/E2 in serum. The percentage of sperm head defeet of group Ⅰ was significantly higher than that of group Ⅲ (t=2. 482, P=0. 016) and that of sperm neck defect of groups Ⅰ and Ⅱ were significantly higher than that of group Ⅲ (t=4.113, 2. 050, P=0.000, 0. 046, respectively). The percentage of sperm tail defect among 3 groups was significantly different (t=2. 722, 3. 996, 3. 110, P=0. 008, 0. 000, 0. 003, respectively). The SDI of group Ⅱ was significantly higher than that of group Ⅰ (t= -2. 293, P= 0. 025). But the TZI increased gradually with the increase of the serum T/E2 and the TZI of groups Ⅱ and Ⅲ were significantly higher than that of group Ⅰ (t=2. 285, 2. 727, P=0. 025, 0. 009, respectively). The percentage of the men in group Ⅰ whose partners became pregnant was 29. 5% and those of groups Ⅱ and Ⅲ were 50% and 42.9%, respectively. Although the percentage among three groups was not different statistically (x2 = 3. 285, 0. 854, 0. 199, P= 0. 070, 0. 355, 0. 655, respectively), the relative risks of groups Ⅱ and Ⅲ were 2.4 and 1.8 times of that of group Ⅰ. There were 25, 15, 7 cases of idiopathic infertility among the 3 groups, respectively. The relative risk of I group was 1.5 and 1.3 times of that of Ⅱ and Ⅲ groups. The correlation analysis showed that the T/E2 in serum had significantly negative correlation with the percent of the sperm head or neck or tail defects (r= -0. 209, -0. 316 and -0. 335,respectively and P= 0. 048, 0. 002 and 0. 001, respectively). Conclusions The decrease of T/E2 in serum was correlative with the decrease of fertility probability, but it did not alter the sperm density and the sperm motility. It showed that the level of the T/E2 in serum was important for spermatogenesis and sperm fertilizing capability.