Somatic and reproductive outcomes in mice treated with cyclophosphamide in pre-pubertal age

Disruption in the normal timing of female puberty, such as in pre-pubertal cancer treatments, can cause abnormal somatic development. We sought to evaluate the impact of cyclophosphamide (CTX) on the somatic, uterine, and ovarian, development of pre-pubertal mice. Pre-pubertal (day 18 of life) C57BL/6J female mice were randomized to receive placebo (group 1A and 1B), 200?mg/kg CTX (group 2A), or 120?mg/kg CTX (group 2B). Mice were euthanized on day 56 (A groups) or 95 (B groups) of life. Body weight and length, uterine and ovarian weight and right femur length and weight were measured, and ovarian insufficiency was assessed. Data were analyzed using ANOVA and t-test. Body weight and length did not differ among groups at time of euthanasia. The femur was shorter and weighed less in mice treated with CTX than in controls. Uterine weight was lower in group 2B than 1B (46.1?mg, 95% CI: 42.9-49.4, vs. 62.2?mg, 95% CI: 58.5-65.8, respectively; p?=?0.005) and was lower in mice that developed ovarian insufficiency than in mice that did not (p?<?0.05). Ovarian weight was lower in mice treated with CTX, regardless of whether they developed ovarian insufficiency. Even with no observable effect on adult body length and weight, CTX treatment in pre-pubertal mice appears to negatively affect femur, uterine, and ovarian development. However, uterine development seems to be dependent on the hormonal status created by CTX more than on its direct effect.     

锰中毒对新生小鼠脑发育的影响

为研究锰中毒对新生小鼠脑发育的影响 ,经口服和腹腔注射联合途径给新生昆明种小鼠染锰。结果显示 :(1)高锰组小鼠体重增长明显滞后 ,脑重和脑重 体重比值显著降低 ;(2 )在Morris水迷宫的行为检测试验中 ,高锰组小鼠前 5天每天到达潜台的平均时间显著延长 ;而在第 6天的探测试验中 ,其在原潜台象限的游泳时间则明显缩短 ;(3)高锰组小鼠的脑组织蛋白质含量明显降低 ,而乙酰胆碱酯酶活性则升高 ;(4)染锰组 ,特别是高染锰组小鼠海马CA3区的胶质细胞纤维酸蛋白免疫反应强度及其阳性产物的平均相对密度均比对照组明显增高。     

Serum lipids in postmenopausal or perimenopausal women using estrogen alone, estrogen with levonorgestrel, or estrogen with norethisterone, compared with nonusers: results from a cross-sectional study in two Norwegian counties 1985-1988

The aim of this study was to compare, in a population setting of postmenopausal or perimenopausal women aged 40 to 54, the levels of serum lipids in women using different hormone replacement therapy (HRT) regimens with women using no sex hormones. There was no unequivocal tendency of a more healthy lifestyle among those using HRT than among nonusers. Any type of regimen was associated with a lower mean level of total and calculated low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol was 0.08 mmoI/L (5.2%) higher in those using estrogen alone, 0.07 mmoI/L (4.5%) higher in users of HRT with norethisterone, and 0.07 mmol/L (4.5%) lower in users of HRT with levonorgestrel, compared with nonusers. The ratio of total-to-HDL cholesterol was lower by 0.37 (6.1%) in those using estrogen alone, by 0.65 (12.3%) in those using HRT with norethisterone, and by 0.24 (5.3%) in those using estrogen with levonorgestrel. There was no association between body mass index and HDL-cholesterol among women who used HRT with norethisterone, whereas an inverse relationship was present in those using estrogen alone and in nonusers (P [interaction] < 0.05).     

Postmenopausal estrogen use and invasive versus in situ breast cancer risk

To examine the effect of cancer histopathology on the relationship between estrogen-replacement therapy (ERT) use and breast cancer risk, we performed a case-control study of 109 postmenopausal women 45 years or older with in situ or invasive breast cancer matched to 545 controls. When in situ and invasive tumors were combined, the overall odds ratio (OR) describing the association between ERT use and breast cancer risk was not statistically significantly elevated (adjusted OR = 1.48, 95% confidence interval [CI] = 0.89–2.47). When the analyses were confined to women with invasive disease, risk estimates were uniformly higher (adjusted OR = 1.85, 95% CI = 1.00–3.45). In contrast, the overall estimate for the relationship between ERT use and in situ breast cancer was close to 1 (adjusted OR = 1.08, 95% CI = 0.42–2.77). The positive association between ERT use and invasive breast cancer we observed, and the lack of association in women with in situ disease, may represent a distinct biological difference or may be related to the small sample size of our study.     

雌激素与认知功能关系的研究进展

认知功能下降是阿尔茨海默病的前期临床表现,随着人口老化,其发病率逐年增加,且女性多于男性.研究雌激素与认知功能的关系,包括注意、再认识、学习、记忆、语言、逻辑推理、解决问题的能力,其它高级智能及精神运动功能等多个方面的问题.对提高绝经后妇女生殖健康水平及生活质量,指导临床用药有重要的意义.     

小鼠出生后接触锰对脑发育的毒性影响

为探讨小鼠出生后接触锰对发育相关指标的毒性的影响，用神经行为试验检测肌力，自发性活动和精神焦虑性，以神经生化TAB法检测全脑过氧化脂质（LPO）含量，邻苯三酚自氧化法检测超氧化物歧化酶（SOD）活性；以细胞免疫化学法（ABC法）检测大脑皮质齿状回胶质细胞纤维酸蛋白（GFAP）免疫反应强度，结果表明：（1）高锰组小鼠身长（头－臀）的增长明显滞后于对照组和低锰组，而低锰组与对照组之间无明显差异；（2）在Morris水迷宫的肌力测试中，染锰组小鼠到达平台的潜伏期明显比对照组延长，且以高锰组更为显著，在旷场试验中，染锰组小鼠在中央和外周爬格子数及抬头探测的次数均明显多于对照组，在Elevated Plus Arms焦虑性试验中，染锰组小鼠从中央区进入第一臂的潜伏期均明显缩短，而进入开放臂次数／入臂总次数的比值则均比对照组显著增高；（3）染锰组小鼠全脑组织LPD含量均比对照组明显升高，而SOD活性则次数的比值则均比对照组显著增高；（3）染锰组小鼠全脑组织LPO含量均对照组明显升高，而SOD活性则明显降低，且均以高锰组更为显著；（4）染锰组小鼠大脑皮质齿状回的GFAP免疫反应强度及其阳性产物的平均相对密度均比对照组明显增强，且以高锰组更为显著，提示小鼠出生后接触锰对其生长发育过程中的体重增长，神经行为，全脑LPO含量与SOD活性，及大脑皮质齿状回GFAP免疫反应均产生了明显的毒性影响。     

环磷酰胺处理对小鼠受精卵和二细胞期胚胎组蛋白H3K9乙酰化修饰的影响

目的用环磷酰胺处理雄性小鼠,是否会对受精后的受精卵及早期胚胎的表观遗传特征组蛋白H3K9乙酰化修饰产生明显影响。方法 5只性成熟ICR雄性小鼠用环磷酰胺注射处理4 d时间作为环磷酰胺处理组,另外5只雄鼠注射相应体积的生理盐水作为正常对照组。雄鼠与雌鼠交配后收集原核期受精卵和二细胞期胚胎,然后用间接免疫荧光染色技术结合激光共聚焦扫描显微镜技术检测胚胎细胞中组蛋白H3K9乙酰化修饰的分布和水平。结果正常对照组中,受精卵的雌雄原核均呈现较明显的H3K9乙酰化染色,至二细胞期时,单个核内的染色水平有所下降,H3K9乙酰化在细胞核内除核仁外的区域相对均匀分布。在环磷酰胺处理组中,大部分原核期受精卵和二细胞期胚胎组蛋白H3K9乙酰化水平和分布模式与正常对照组胚胎没有明显差异,只有少部分(25%)受精卵呈现比较大的雄原核以及相对较低的乙酰化染色水平;37%二细胞期胚胎发生碎化,形成2～3个相对大一些的乙酰化染色水平很低的细胞以及若干小的球状体。结论高剂量环磷酰胺处理雄鼠可以在一部分受精卵和早期卵裂胚中导致表观遗传特征和胚胎发育的异常。     

氯化锰处理小鼠精子质量的变化

目的研究用氯化锰处理的小鼠精子质量的变化.方法雄性小鼠经腹腔注射不同剂量氯化锰水溶液,1次/d,连续处理5d和35d,检测精子数、精子活动度、精子畸形率和睾丸初级精母细胞染色体畸变率,并测定雄性小鼠的生殖力和雌性小鼠的受孕率.结果氯化锰20mg/kg和40mg/kg染毒组精子计数、活精率显著或极显著低于对照组(P＜0.05;P＜0.01);精子畸形率、睾丸初级精母细胞染色体畸变率显著和极显著高于对照组(P＜0.05,P＜0.01);各染毒组雄性小鼠交配率、雌性小鼠受孕率显著或极显著低于对照组(P＜0.05,P＜0.01).结论氯化锰处理使得小鼠的精子质量明显改变,雄性小鼠生殖力下降可能与其精液质量改变有关.     

多菌灵对小鼠精子形态及雄鼠生育力的影响

研究结果表明,连续五天灌胃,多菌灵剂量在120mg/kg以上,能诱导小鼠的精子畸形率增高,且存在剂量—反应关系。饲料中掺药喂养2个月,多菌灵400mg/kg饲料以上,对交配率、受孕率影响不大,但引起早期胚胎死亡率增加。     

雌激素受体亚型在多囊卵巢综合征发病中的作用

雌激素受体是核受体超家族成员之一,其有两种亚型:雌激素受体α和雌激素受体β.两种亚型在结构上有高度的同源性,但是组织分布和各组织成分中的表达明显不同,与配体结合后产生的生物效应也不同.二者表达及比例变化与组织的功能和病理变化有关.研究雌激素受体α和雌激素受体β的结构及其在女性生殖系统中的分布和功能,探讨其与多囊卵巢综合征的关系,对了解雌激素受体亚型的分布与功能的关系,以及分布的变异和异常调节与多囊卵巢综合征的关系都有重要意义.     

醋酸铅对小鼠精子毒作用和雄性生育力的影响

本文通过慢性经口染毒试验,观察了醋酸铅对雄性小鼠的精子形态、精子数量、精子运动能力和雄性生育力的影响,及生殖器官的组织病理学改变。结果表明,饲以1%醋酸铅饲料3个月可出现精于畸形率增高,血铅明显升高;2%醋酸铅可使精子运动能力下降,精子计数减少,睾丸出现轻度损伤;4%醋酸铅可影响雄性生殖机能,平均活胎数减少,总死胎率升高。提示醋酸铅对雄性小鼠生殖细胞有潜在的诱变能力,并能使雄性生育力降低。     

Voluntary consumption of ethanol and its consequences in C57 mice treated with 4-methylpyrazole

Daily injections of the alcohol dehydrogenase inhibitor 4-methylpyrazole (4MP) were administered to C57BL/6J mice offered continuous free access to food, water and 10% v/v ethanol. There was a significant correlation (r = -0.82) between the rate of ethanol consumption during pretreatment and the effect of 4MP on subsequent intake. Mice drinking more than 2.5 g/kg per day decreased their intake, while subjects drinking less than this amount increased the quantity of ethanol self-administered. The elevated concentrations of plasma ethanol which resulted from voluntary consumption were sufficient to produce intoxication but did not induce physical dependence. Presenting mice with 10% ethanol as their only fluid or offering them a choice of water and saccharin-sweetened ethanol increased intake but failed to raise plasma ethanol to the concentrations observed in mice offered unflavored ethanol and water, and treated with 4MP. The evidence suggests that plasma ethanol does not limit voluntary drinking in untreated mice and that concentrations of 135 to 250 mg/dl are not avoided by C57 mice in a free-choice situation.     

子宫内膜癌组织中雌孕激素受体蛋白表达及其与临床病理因素分析

目的 探讨雌、孕激素受体在子宫内膜癌中的表达及其与预后的相关性.方法 选取于广西河池市人民医院就诊的子宫内膜癌患者40例,采用免疫组化法检测所有患者癌组织中的雌激素受体(ER)及孕激素受体(PR).比较ER及PR在不同组织学类型及不同分期的子宫内膜癌患者中的表达情况.结果 40例子宫内膜癌患者中,ER阳性30例(75.00%),阴性10例(25.00%),PR阳性29例(72.50%),阴性11例(27.50%).手术-病理分期Ⅰ期ER、PR阳性率显著高于Ⅲ期(χ2值分别为3.987、3.987,均P<0.05).组织学分化高分化ER、PR阳性率显著高于低分化(χ2值分别为5.831、4.093,均P<0.05),且中分化ER阳性率显著高于低分化(χ2=4.804,P<0.05).肌层浸润程度ER、PR阳性率均无显著性差异(χ2值0.087~2.264,均P>0.05).有淋巴结转移者ER、PR阳性率显著高于无淋巴结转移者(χ2值分别为5.840、4.675,均P<0.05).结论 ER及PR在子宫内膜癌组织中的表达与手术-病理分期及组织学分化程度相关,ER及PR在手术-病理分期越早,组织学分化越高的患者中的阳性率越高.     

SD大鼠的繁殖性能及子代生长发育情况

目的对浙江省医学科学院实验室已有生殖毒性资料进行统计分析,以研究SD大鼠繁殖性能特征,分析仔鼠在断乳前的生长发育情况,并比较雌雄仔鼠生长发育的差异。方法对已有历史数据即8个批次两代繁殖毒性试验对照组数据进行统计分析。观察终点包括受孕情况、产仔情况、窝重、窝大小、断乳前仔鼠体重,采用excel软件对相关数据进行统计学分析。结果 SD大鼠妊娠周期为22～25 d,交配行为集中分布在第1个动情周期。交配成功率为94.27%（87.50%～100.00%）,受孕率为92.19%（87.50%～100.00%）,活产率为98.81%（95.24%～100.00%）,出生存活率为94.67%（87.78%～99.14%）,哺育成活率为95.85%（89.74～98.82%）。出生0、4、7、14、21 d仔鼠平均体重分别为（6.54±0.64）g、（10.66±1.72）g、（16.74±2.42）g、（32.93±5.28）g、（51.64±6.59）g。其中雌性仔鼠的平均体重分别为（6.40±0.58）g、（10.48±1.62）g、（16.47±2.32）g、（32.41±4.02）g、（50.72±6.49）g,雄性仔鼠的平均体重分别为（6.68±0.70）g、（10.86±1.84）g、（17.05±2.55）g、（33.05±4.37）g、（52.59±7.05）g;两者差异有统计学意义（P〈0.05）。结论 SD大鼠各项繁殖指数均较高,适合用于开展生殖毒性试验。研究发现,哺乳期雌雄仔鼠体重已存在明显的差异,分别将雌雄仔鼠体重等相关参数进行统计分析,能更好地反映大鼠生殖毒性研究结果。     

Ethanol consumption in mice: relationships with circadian period and entrainment

A functional connection between the circadian timing system and alcohol consumption is suggested by multiple lines of converging evidence. Ethanol consumption perturbs physiological rhythms in hormone secretion, sleep, and body temperature; and conversely, genetic and environmental perturbations of the circadian system can alter alcohol intake. A fundamental property of the circadian pacemaker, the endogenous period of its cycle under free-running conditions, was previously shown to differ between selectively bred high- (HAP) and low- (LAP) alcohol preferring replicate 1 mice. To test whether there is a causal relationship between circadian period and ethanol intake, we induced experimental, rather than genetic, variations in free-running period. Male inbred C57Bl/6J mice and replicate 2 male and female HAP2 and LAP2 mice were entrained to light:dark cycles of 26 or 22 h or remained in a standard 24 h cycle. On discontinuation of the light:dark cycle, experimental animals exhibited longer and shorter free-running periods, respectively. Despite robust effects on circadian period and clear circadian rhythms in drinking, these manipulations failed to alter the daily ethanol intake of the inbred strain or selected lines. Likewise, driving the circadian system at long and short periods produced no change in alcohol intake. In contrast with replicate 1 HAP and LAP lines, there was no difference in free-running period between ethanol naïve HAP2 and LAP2 mice. HAP2 mice, however, were significantly more active than LAP2 mice as measured by general home-cage movement and wheel running, a motivated behavior implicating a selection effect on reward systems. Despite a marked circadian regulation of drinking behavior, the free-running and entrained period of the circadian clock does not determine daily ethanol intake.     

325例辅助受孕儿24月龄时精神运动发育水平研究

【目的】 通过研究辅助受孕儿24月龄时的精神运动发育水平,以评价辅助生殖技术的安全性。 【方法】 采用前瞻性对照研究方法,实验组为人工辅助受孕妊娠儿,对照组为自然受孕妊娠儿,将两组人群在母亲年龄、产次、家庭社会阶层、双亲受教育程度等几个方面进行配对,均自母亲孕28周起入组登记定期随访收集相关资料并由经过培训的指定专业人员采用CDCC婴幼儿发育量表定期对其行精神运动发育评估至24月龄,获得智力发育指数及运动发育指数。 【结果】 辅助受孕儿童至24月龄时其精神运动发育水平与自然受孕儿童相比差异无统计学意义(P>0.05)。 【结论】 辅助受孕儿童24月龄时的精神运动发育水平正常,初步证明我国目前的辅助生殖技术是安全的。     

Efficacy and safety of a 28-day oral contraceptive with 7 days of low-dose estrogen in place of placebo

BACKGROUND: The study was conducted to evaluate the efficacy and safety for the prevention of pregnancy of a 28-day oral contraceptive (OC) containing 150 mcg desogestrel (DSG)/20 mcg ethinyl estradiol (EE) for 21 days followed by 7 days of 10 mcg EE (Cette-28). STUDY DESIGN: A 6-month, prospective, multicenter, single-arm study was conducted in 1302 women aged 18-45 years. RESULTS: Over six cycles of treatment, the cumulative risk of pregnancy among all treated subjects (n=1262) was 0.9%. The Pearl Index for women 18-35 years of age (n=1042) was 2.20, including 9 pregnancies with estimated conception dates during active drug ingestion or up to 7 days after the last combination tablet. The rate of unscheduled bleeding was low and the duration of scheduled bleeding was approximately 2 days during each of the six treatment cycles. The safety profile was similar to what has been reported for other OCs. CONCLUSION: This low-dose, 28-day OC incorporating 7 days of 10 mcg EE during the hormone free interval is effective and safe for the prevention of pregnancy and is well-tolerated by women.     

Preferred frequency and characteristics of menstrual bleeding in relation to reproductive status, oral contraceptive use, and hormone replacement therapy use

This study addresses attitudes towards changes in menstrual bleeding patterns caused by oral contraceptives (OC) or hormone replacement therapy (HRT) and preferred changes in bleeding pattern with and without use of OC or HRT in relation to reproductive age group. Data were collected by means of telephone interviews with 325 women in each of four age groups (15–19, 25–34, 45–49, and 52–57 years). In total, 80.5% of currently menstruating women preferred one or more changes in bleeding pattern such as less painful, shorter, or less heavy periods, or amenorrhea. The majority of the menstruating women in all age groups preferred to have a bleeding frequency of less than once a month or never, whether the bleeding was spontaneous or induced by OC. In the case of HRT, amenorrhea was most preferred. These findings with respect to preferred bleeding frequency and OC may have important implications for health care providers and for future contraception development.