Gestational exposure to hydroxyprogesterone caproate suppresses reproductive potential in male rats

Hydroxyprogesterone caproate was administered to pregnant rats at a dose level of 10 and 25 mg/kg body weight on 1st, 7th and 14th gestational day and the male pups (F1 generation) were allowed to grow for 90 days. The effect of gestational exposure to hydroxyprogesterone caproate on fertility was assessed by breeding F1 male rats with control female rats besides analyzing sperm quality and quantity in F1 male rats. The number of implantation sites and viable fetuses was significantly reduced in females mated with F1 males that were exposed to hydroxyprogesterone caproate during embryonic development. The decrease in sperm function was associated with a decrease in sperm motility, sperm viability and sperm count in F1 rats. The study clearly indicates that in utero exposure to hydroxyprogesterone caproate affects fertility in male rats.     

Effect of prenatal exposure to hydroxyprogesterone on steroidogenic enzymes in male rats

Pregnant Wistar strain albino rats were administered hydroxyprogesterone and the steroidogenic potential of the testis was analysed in the next generation adult male rats. In utero exposure to supranormal levels (10 mg/kg body weight or 25 mg/kg body weight) of hydroxyprogesterone decreased the activity levels of marker steroidogenic enzymes (3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase) of adult (mature) rat testis. Hydroxyprogesterone mediation in the suppression of rat testicular steroidogenesis is suggested, which can be correlated to the observed decrease in male reproductive potential in mammals exposed to female hormones during embryonic development.     

铅暴露对雄性黑斑蛙精子毒性和血清性激素水平的影响

在实验条件下,将健康性成熟雄性黑斑蛙暴露于0.1、0.2、0.4、0.8和1.6 mg·L-1浓度的铅溶液中30d,观察和分析黑斑蛙的精子数量、精子活动度和精子畸形率,采用酶联免疫吸附法检测血清中睾酮(T)和雌二醇(E2)的水平,以探讨铅对雄性黑斑蛙的生殖内分泌毒性.结果表明,随铅染毒剂量的升高,精子数量下降,精子畸形率呈剂鼍依赖性增加,精子活动率呈剂鼍依赖性降低;随铅染毒剂量的升高,血清中T水平明显下降,E2水平则明显升高,且均呈剂量-效应关系,结果提示,铅对雄性黑斑蛙有明显的生殖毒性,可改变血清睾酮和雌激素水平,干扰生殖内分泌调节平衡.     

Suppression of male reproduction in rats after exposure to sodium fluoride during early stages of development

Sodium fluoride (NaF), a widespread natural pollutant was given to sperm-positive female rats throughout gestation and lactation at a dose of 4.5 and 9.0 ppm via drinking water. The neonates were allowed to grow up to 90 days on tap water, and then sperm parameters, testicular steroidogenic marker enzyme activity levels, and circulatory hormone levels were studied. The sperm count, sperm motility, sperm coiling (hypoosmotic swelling test), and sperm viability were decreased in experimental rats when compared with controls. The activity levels of testicular steroidogenic marker enzymes (3β hydroxysteroid dehydrogenase and 17β hydroxysteroid dehydrogenase) were significantly decreased in experimental animals indicating decreased steroidogenesis. The serum testosterone, follicle stimulating hormone and luteinizing hormone levels were also significantly altered in experimental animals. Our data indicate that exposure to NaF during gestation and lactation affects male reproduction in adult rats by decreasing spermatogenesis and steroidogenesis.     

双酚A类似物的雄性生殖毒性研究进展

聚焦BPA类似物对雄性动物的生殖毒性研究,分析双酚S、双酚F、双酚AF、双酚B和双酚E对哺乳类实验动物睾丸及组织结构、附睾重量及组织学结构、激素水平、精子参数等常规指标的影响,考察关于鱼类和两栖类动物的研究.研究发现,不管暴露剂量高低、暴露方式的差异或是动物种属的不同,所有BPA类似物的暴露都显示阳性结果,这与BPA雄性生殖毒性尚有争议的事实形成对比,暗示这些BPA类似物具有比BPA更明显的雄性生殖毒性.总体来看,目前的BPA类似物雄性生殖毒性的数据只局限在有限的几个实验室,且实验的质量控制难以评价.因此,BPA类似物的雄性生殖毒性的数据还需要更多实验室的验证,并且过程中需要严格控制动物实验的质量,以获得更加可靠且可重复的结果.     

Prenatal sex diagnosis: Testosterone and fsh levels in mid-trimester amniotic fluids

We studied the validity of mid-trimester amniotic fluid testosterone and FSH in the diagnosis of fetal sex in abnormal fetuses and in twins. It was found that the testosterone/FSH ratio, but not the level of the individual hormones, was an excellent criterion for fetal sex diagnosis. In a control group of 32 female and 34 male fetuses, the testosterone/FSH ratio was diagnostic. In two cases the values were indeterminate and fetal sex could not be predicted, but there were no false diagnoses. The abnormalities of the fetuses were diagnosed by karyotype analyses or raised levels of α-fetoprotein. It was found that neither autosomal trisomies nor X-chromosome aneuploidy or neural tube defect interfered with the diagnostic value of the hormonal approach. The twin study included 14 pairs, three of whom were discordant for sex. In all twins the fetal sex diagnosis was appropriate. In co-twins of the same sex the hormone levels were very close to each other.     

Behavioural and physiological consequences of male reproductive trade-offs in edible dormice (Glis glis)

Testosterone mediates male reproductive trade-offs in vertebrates including mammals. In male edible dormice (Glis glis), reproductivity linked to high levels of testosterone reduces their ability to express torpor, which may be expected to dramatically increase thermoregulatory costs. Aims of this study were therefore to analyse behavioural and physiological consequences of reproductive activity in male edible dormice under ecologically and evolutionary relevant conditions in the field. As we frequently encountered sleeping groups in the field, we hypothesized that social thermoregulation should be an important measure to reduce energy expenditure especially in sexually active male edible dormice. Our results revealed that the occurrence of sleeping groups was negatively influenced by male body mass but not by reproductive status or ambient temperature. In reproductive as in non-reproductive males, the number of individuals huddling together was negatively influenced by their body mass. Thus in general males with a high body mass were sitting in smaller groups than males with a low body mass. However, in reproductive males group size was further negatively affected by ambient temperature and positively by testes size. Thus breeders formed larger sleeping groups at lower ambient temperatures and males with larger testes were found in larger groups than males with smaller testes. Measurements of oxygen consumption demonstrated that grouping behaviour represents an efficient strategy to reduce energy expenditure in edible dormice as it reduced energy requirements by almost 40%. In summary, results of this field study showcase how sexually active male edible dormice may, through behavioural adjustment, counterbalance high thermoregulatory costs associated with reproductive activity.     

Endosulfan is toxic to the reproductive health of male freshwater fish, <Emphasis Type="Italic">Cyprinion watsoni</Emphasis>

Endosulfan is an organochlorine pesticide that is toxic to aquatic life. Endosulfan might hamper the reproductive health of indigenous fish in agricultural areas of Pakistan where this pesticide is sprayed widely. The aim of the current study is to investigate the toxic effects of endosulfan on selected reproductive parameters of male freshwater fish, Cyprinion watsoni. Two concentrations of endosulfan (0.5 and 1 ppb for 30 days exposure) were tested for their effects on body weight, body length, and testicular weight, length, and width. Testicular testosterone was assayed from tissue extracts using enzyme immunoassay (EIA). A significant increase in the mortality rate was observed in both treated groups during both spawning and quiescent seasons. The overall behavior of fish in the aquarium was normal in all control and treated groups. However, the treated fish exhibited anxiety after treatment with endosulfan. The body weight and length, and testicular weight, length and width were not significantly different to the control group. The testicular testosterone concentrations were significantly lower in both endosulfan-treated groups compared to the control. The decrease was dose-dependent, with a significant difference between the two treated groups. The histomorphological results demonstrated various testicular alterations in the treated groups. These alterations included an increase in interlobular areas and clumping patterns in spermatocytes/spermatids. Because spermatids eventually differentiate into sperms, their low count will directly result in lower sperm count. Taken together, these results suggest that endosulfan is a toxicant that at least disturbs testosterone levels (possibly others) and negatively impacts the reproductive health of male freshwater fish.     

乙炔基雌二醇对真鲷幼鱼的雌激素效应研究

采用静态暴露方式研究17α-乙炔基雌二醇(EE_2)对真鲷(Pagrosomus major)幼鱼的雌激素效应.当真鲷幼鱼暴露于0.01、0.1、0.5 μg/L EE_2,42 d后,真鲷幼鱼的肥满度极显著下降;血浆中卵黄蛋白原(Vtg)被诱导产生,肝胰脏指数(HSI)和血浆蛋白总量极显著升高;血浆雌二醇(E_2)和睾酮(T)水平显著降低,其中血浆雌二醇受EE_2的干扰更显著,降低的幅度更大.结果提示,真鲷幼鱼的肥满度、肝胰脏指数、血浆蛋白总量、血浆性激素水平等可作为评估EE_2等环境内分泌干扰物毒性效应的生物指标;真鲷幼鱼血浆中的Vtg具有作为生物标志物,用于监测海洋水体中EE_2等环境内分泌干扰物的潜力.     

金雀异黄素对雄性斑马鱼卵黄原蛋白mRNA的诱导机理

采用质量浓度分别为1、10、100、1 000 μg/L的金雀异黄素对成年雄性斑马鱼进行水体暴露28 d,通过real-time PCR技术检测雄性斑马鱼肝脏内Vtg-1(卵黄原蛋白)、ERα和ERβ1 mRNA(雌激素受体)的表达水平,并利用同位素放射免疫法检测雄性斑马鱼性腺w(睾酮)和w(E₂)(E₂为17β-estradiol,17β-雌二醇). 结果表明:10~1 000 μg/L金雀异黄素显著诱导了雄性斑马鱼肝脏Vtg-1 mRNA的表达,二者呈剂量-效应关系,同时显著上调了雌激素受体ERβ1 mRNA的表达;但1~1 000 μg/L金雀异黄素却极显著地抑制了雄性斑马鱼肝脏内ERα mRNA的表达,同时造成雄性斑马鱼性腺w(E₂)的升高和w(睾酮)的降低. 研究结果显示,金雀异黄素可能通过提高雄性斑马鱼体内ERβ1mRNA的表达和内源w(E₂),增强ERβ1对内源雌激素的介导作用,从而促进Vtg-1的表达.      

低剂量全氟辛酸对雄性黑斑蛙生殖毒效应及机理研究

针对新型环境有机污染物全氟辛酸(PFOA)对两栖动物的毒效应问题,以黑斑蛙(Rana nigromaculata)为实验对象,研究了低剂量PFOA暴露对雄性黑斑蛙生殖毒效应及机理.结果表明,在0.001～1mg.L-1低剂量体外暴露20d条件下,PFOA能够显著诱导黑斑蛙精子发生畸形,相对于对照组,精子畸形率呈现明显的剂量-效应关系.酶联免疫试剂盒检测发现,除0.001mg.L-1诱导组外,0.01、0.1和1mg.L-1暴露组的血清雄性激素睾酮和雌性激素雌二醇含量分别显著降低(p<0.01,F=288.7)和上升(p<0.01,F=289.0),说明PFOA作用下黑斑蛙体内性激素水平受到改变.采用荧光定量PCR技术进行进一步的分子生物学检测,发现与性激素水平密切相关的两个基因P450芳香化酶和类固醇激素合成因子(SF-1)均增强表达(0.001mg.L-1诱导组,p<0.05;0.01、0.1和1mg.L-1暴露组,p<0.01,F=140.8).全氟辛酸对两栖类动物的雄性生殖毒效应机理主要是通过介导与性激素分泌相关的两个重要基因P450芳香化酶和类固醇激素合成因子,使其表达上调,从而一方面抑制睾酮的产生,另一方面促进性激素雌二醇的分泌.在0.001mg.L-1的体外暴露剂量下,PFOA就能够明显诱导黑斑蛙精子产生畸形毒性及增强P450芳香化酶和SF-1基因的表达(p<0.05),因此,为保护两栖动物种群,在制订PFOA地表水环境质量标准时应当考虑其下限不能低于0.001mg.L-1.     

Combined effect of tributyltin and benzo[a] pyrene on the levels of sex hormone and vitellogenin in female Sebastiscus marmoratus

Tributyltin（TBT）, an organometal used as an antifouling biocide, has been reported to induce masculinization of fish. Benzo [a]pyrene （BaP）, a widespread carcinogenic polycyclic aromatic hydrocarbon, has been reported that its microsomal metabolites can produce an estrogenic response when tested in vitro. This study was therefore designed to examine the potential in vivo influence of TBT, BaP and their mixture on sex hormone levels in serum of Sebastiscus marmoratus, which were given 2 separate intraperitoneally （ip） injections（a single injection every 7 d） of TBT（0.5, 1, 5 and 10 mg/kg）, BaP（0.5, 1, 5 and 10 mg/kg）, or both in combination（0.5, 1, 5 and 10 mg/kg）; control fish received olive oil vehicle only. Six days after the 2nd injection, serum samples were collected and analyzed for sex hormone levels and alkali labile protein phosphorus （ALPP）, which is related to the yolk precursor protein vitellogenin. The pollutants at all doses significantly reduced serum testosterone, estradiol and ALPP content after 2 injections compared with the corresponding controls. The reduction of the estradiol levels should be response for the decrease of the vitellogenin levels. The results in the present study suggested that aromatase seems not the major target acted by TBT and BaP in fish. This study demonstrated that TBT or BaP exposure both inhibit the reproductive potential in female Sebastiscus marmoratus. Combined effect of TBT and BaP on the serum testosterone, estradiol and ALPP was not antagonism from the anticipation.     

The endocrine pharmacology of testosterone therapy in men

The review starts off by outlining the history of the discovery of the male sex hormone testosterone and the historical background to the various, often dubious, approaches to the treatment of age-related endocrine disorders in older men. A discussion of congenital androgen deficiency in young men is followed by methods of diagnosing hypogonadism in older men. Among therapeutic options, the alternatives to direct testosterone replacement are discussed, although none of them have proved to be particularly successful in clinical practice. For testosterone replacement itself, various routes of administration and pharmaceutical formulations are now available, facilitating good monitoring and individualized therapy.     

妊娠期全氟辛酸染毒对子代雄鼠发育毒性的研究

探讨妊娠期染毒全氟辛酸(perfluorooctanoic acid,PFOA)对子代雄鼠发育毒性的影响.将50只妊娠0 d小鼠随机分5组,每组10只,妊娠0~17 d每天按0、1、2.5、5和12.5 mg·kg~(-1)BW饲喂PFOA,产后仔鼠正常饲养,记录仔鼠存活数.产后21 d,检测仔鼠血清睾酮水平并计算睾丸指数;HE染色观察睾丸组织结构变化;RT-PCR法检测睾丸组织Dlk1-Dio3印记基因簇各目的基因mRNA的表达情况.结果显示,随PFOA染毒剂量增加,仔鼠存活数显著降低,血清睾酮含量极显著性降低(p0.01);睾丸指数无统计学意义;睾丸组织有不同程度的损伤并呈剂量依赖性;Dlk1-Dio3印记基因簇各目的基因的表达量都有降低趋势,其中Gtl2、Rian、Dio3均显著性降低(p0.05).结果表明,妊娠期染毒PFOA能够降低仔鼠存活数,损伤睾丸组织结构,并能够扰乱生殖激素,降低睾丸组织Dlk1-Dio3印记基因簇各目的基因mRNA的表达.     

低剂量长期铅暴露对雄性黑斑蛙精巢组织关键酶活性的影响

在实验条件下,将健康的性成熟雄性黑斑蛙暴露于0.1、0.2、0.4、0.8和1.6mg·L-1的Pb2+溶液中30d,以Ca2+-ATP酶、Na+-K+-ATP酶、Ca2+-Mg2+-ATP酶、β-葡萄糖醛酸苷酶(β-DG)、乳酸脱氢酶(LDH)和酸性磷酸酶(ACP)活性为指标,进行了长期铅暴露对雄性黑斑蛙生殖毒性的研究.结果表明:随着铅染毒剂量的增加,Ca2+-ATP酶和Na+-K+-ATP酶活性被诱导,Ca2+-Mg2+-ATP酶活性被抑制,当Ca2+-Mg2+-ATP酶的抑制程度超过Ca2+-ATP酶和Na+-K+-ATP酶的代偿机制时,会抑制精子的发生,进而导致雄性生殖毒性;在1.6mg·L-1Pb2+处理下,ACP酶被显著抑制,提示支持细胞受损,精子总数受到影响;在0.4mg·L-1Pb2+处理下,LDH酶被显著抑制,提示生精细胞受损,精子质量受到影响.     

氟对斑马鱼生殖毒性研究

为了探讨氟对鱼类的生殖毒性效应,以成年斑马鱼为试验对象,氟化钠暴露45 d和90 d后,运用组织切片观察斑马鱼性腺组织的发育情况,采用酶联免疫分析法测定性腺中雌二醇（Estradiol,E2）、卵黄蛋白原（Vitellogenin,VTG）和睾酮（Testosterone,T）的含量,并使用实时荧光定量PCR方法检测斑马鱼生殖相关基因的表达水平.结果显示：氟暴露会阻滞成年斑马鱼性腺发育,造成卵泡发育不良,精巢生精能力下降;同时降低雌性斑马鱼性腺中E2和VTG的含量,增加T的含量;雌性斑马鱼孕酮受体（Prg）和糖皮质激素受体（GR）基因相对表达量随氟浓度的增加呈先降后升的趋势,随着染毒剂量与时间的增加,雄激素受体（AR）基因相对表达量逐渐增加,而CYP19a基因相对表达量逐渐减少.雄性斑马鱼性腺中E2、VTG、T的含量及生殖相关基因表达的变化趋势则与雌性斑马鱼相反.综上所述,氟暴露可以通过影响斑马鱼体内性腺发育、E2、VTG、T含量及生殖相关基因表达来影响其生殖功能.实验结果可为进一步研究氟化物对水生动物的生殖毒性效应提供理论依据.     

氨基脲诱导的大鼠神经行为毒性及其生化机制

为探究氨基脲（SEM）染毒对SD大鼠的神经行为毒性及其作用机制,将44只SPF级SD雄性大鼠随机分为4组：对照组,SEM低、中、高剂量组,每组11只,分别以0,7.5,15,30mg/（kg·bw）SEM的剂量连续灌胃染毒28d.染毒前后分别通过旷场实验和高架十字迷宫实验测试神经行为.采用液相色谱法测定γ-氨基丁酸（GABA）和谷氨酸（GLU）,ELISA法测定5-羟色胺（5-HT）、去甲肾上腺素（NE）、多巴胺（DA）、单胺氧化酶（MAO）以及N-甲基-D-天氡氨酸受体（NMDAR）含量.结果显示,高剂量染毒组大鼠在旷场实验中运动总距离和中央区域距离显著低于对照组（P<0.05）,各剂量组大鼠在高架十字迷宫实验中进入开臂时间百分比和进入开臂次数百分比均显著低于对照组（P<0.05或P<0.01）.与对照组相比,各染毒组大鼠脑组织中GABA含量和MAO活性均有不同程度降低,而GLU,NMDAR,5-HT,NE和DA水平均有不同程度上升.SEM诱导大鼠神经行为毒性的机制与破坏GABA和GLU的相互转化、增加NMDAR含量以及抑制MAO活性导致单胺类神经递质水平上升3个途径有关.     

四种拟除虫菊酯类农药的环境雌激素活性研究

将金鱼(Carassius auratus)分别暴露于0.1mg/L甲氰菊酯、氰戊菊酯、溴氰菊酯和0.5mg/L氯氰菊酯21d后,尾静脉取血,离心分离获得血浆,利用Western-blot方法检测金鱼血浆中是否有卵黄原蛋白产生,同时测定金鱼生殖腺指数、γ-谷氨酰转移酶和乳酸脱氢酶活性.结果表明,对照组雄性金鱼血浆中未检测到卵黄原蛋白,4种拟除虫菊酯农药均能诱导雄性金鱼分泌卵黄原蛋白,而且溴氰菊酯和氯氰菊酯明显降低了雄鱼生殖腺指数,4种农药均能够明显抑制精巢γ-谷氨酰转移酶和乳酸脱氢酶活性.由此可见,4种拟除虫菊酯类农药具有潜在的环境雌激素活性和生殖毒性.     

Exposure to polycyclic aromatic hydrocarbons and risk for premature ovarian failure and reproductive hormones imbalance

Polycyclic aromatic hydrocarbons (PAHs) are a typical class of persistent organic pollutants that is ubiquitous worldwide. Previous animal studies suggested that PAHs had adverse effects on female reproduction. However, the human data regarding relationship of PAHs exposure with women reproductive health, such as ovarian dysfunction, are scarce. In this case-control study, the associations of serum levels of PAHs with the risk of premature ovarian failure (POF) and reproductive hormones in Chinese women were investigated, with recruiting 157 POF patients and 217 healthy women. The serum levels of 12 types of PAHs, as well as reproductive hormones, including follicle-stimulating hormone, luteinizing hormone and anti-mullerian hormone, were determined. In the logistic regression models, most individual PAH congeners showed significantly positive correlations with the risk of POF (p < 0.05), except for fluorine and pyrene. Benzo(a)pyrene (BaP), as the most carcinogenic PAH congener, was observed to be significantly positively associated with the risk of POF. After adjustment for age, body mass index, educational levels and household income, per one-unit increase in the log-transformed BaP concentration was significantly correlated with 2.191-fold increased risk of POF (OR = 2.191, 95%CI: 1.634–2.938, p < 0.05). To the best of our knowledge, this is the first study to report an association between internal exposure levels of PAHs and the increased risk of POF in women.     

Geschlechtsbestimmung und Geschlechtsdifferenzierung

Sex determination in mammals proceeds like a cascade from the level of the sex chromosomes to the gonads, to the genital ducts, and finally to the expression of the male or female phenotype. At the level of the genital ducts male sex organs are induced by testosterone. Its action depends on an intact cytoplasmic androgen receptor protein. The testicular feminization mutation (Tfm) leads to loss of hormone binding capacity. Individuals with testes but female external phenotype develop. In the mouse the interaction of androgen insensitiveTfm cells with normal cells can be studied in mosaic individuals composed of both cell types, and in organ culture by recombination ofTfm and normal tissues. The experiments show that under the action of testosterone the normal cells express male differentiated cellular functions, whereas theTfm cells differentiate in female direction. In respect to proliferation and expression of male or female organ structures, however, both cell types communicate via local factors. Thus, instead of irregular malformations intersex organs develop.