内分泌干扰物MXC对生殖和胚胎发育的影响

日趋增加的环境和工业化合物,最近已被定义为具有内分泌活性的环境内分泌干扰化合物,对人类健康产生了严重的危害.尤其是类似雌激素作用的环境内分泌干扰物引起动物生殖变异、出生缺陷和威胁人类生殖内分泌健康,在最近几年里已引起人类学家的日趋重视.甲氧滴滴涕是具有雌激素活性的非甾体杀虫剂,对胚胎和生殖发育有潜在危险.该文就甲氧滴滴涕对生殖和胚胎的毒性作用进行综述.     

环境激素类农药甲氧滴滴涕生殖毒性研究进展

随着我国农业的发展，杀虫剂六六六、DDT和除草剂乙草胺等内分泌干扰物类农药用量不断增长。目前，DDT已经被甲氧滴滴涕广泛替代，但后者依然具有雌激素样作用，能干扰多种动物的内分泌系统，影响生殖、免疫、神经、心血管等系统的功能。本文根据相关文献资料，对环境激素类农药甲氧滴滴涕的生殖毒性做了综述和介绍，对国内环境激素类农药方面的研究提供参考。     

甲氧滴滴涕对卵巢组织及子代发育的影响

甲氧滴滴涕作为代替滴滴涕的有机氯杀虫剂,在许多国家被广泛使用,但是研究表明甲氧滴滴涕具有弱雌激素样作用,在生物体内可以通过激素受体、氧化应激等多种机制引起生殖系统、中枢神经系统的毒性损害,子代多系统发育异常.该文就其对卵巢组织、子代发育方面的毒性损害及可能的作用机制作以综述.     

慢性砷暴露对大鼠动情周期影响

环境雌激素因其对动物内分泌系统的干扰作用而引起人们广泛关注.它可以导致生殖毒性^[1]、出生缺陷、发育异常和代谢紊乱,对人体多个系统具有毒性效应,并可引发恶性肿瘤.有文献报道砷是内分泌干扰物^[2-3],体外细胞实验证实低剂量三氧化二砷具有雌激素样效应^[4].本研究通过观察不同剂量慢性砷暴露对雌性大鼠动情期及动情周期影响,进一步探讨砷的雌激素样效应.     

有机磷阻燃剂的毒性及其作用机制研究进展

随着溴系阻燃剂的逐步禁用,有机磷酸酯类阻燃剂被广泛应用。近年来随着研究的不断深入,有机磷酸酯阻燃剂（organophosphate flame retardants,OPFRs）带来的环境影响以及对人群健康效应已广受关注,既往研究证实OPFRs具有多种毒性效应,主要表现为神经毒性、内分泌干扰效应、脏器毒性、生殖和发育毒性等。进行OPFRs对生物体神经毒性、内分泌干扰效应、脏器毒性、生殖与发育毒性及相关毒作用机制综述,旨在对OPFRs暴露人群的健康影响提供参考和科学依据。     

三丁基锡内分泌干扰及生殖毒性研究进展

三丁基锡是一种用途广泛的有机锡化合物,在水体、海洋食品和生活用品中均可检测到三丁基锡.内分泌干扰物成为近年来热议的公共卫生问题.三丁基锡对人体健康具有潜在危害,笔者从三丁基锡环境污染、人体暴露、内分泌干扰和生殖毒性方面,对三丁基锡国内外研究资料进行综述,并探讨三丁基锡生殖毒性机制.     

我国邻苯二甲酸酯环境污染现状及对女性（雌性）生殖健康的危害

随着工业的迅速发展，邻苯二甲酸酯类化学物（phthalate esters，PAEs）被广泛用于人们日常生产和生活中。在我国PAEs每年的消耗量超过100万吨，在大气、土壤、水体和生物体中均有不同程度检出。作为公认的环境内分泌干扰物，PAEs对女性（雌性）生殖健康的危害备受关注。以PAEs对我国环境污染现状的研究为基础，从人群研究、动物实验以及毒性作用机制等方面综述了PAEs对女性（雌性）生殖健康危害方面的研究成果。     

环境内分泌干扰物对青春期儿童性发育的影响

环境内分泌干扰物是环境中存在的一类化学物质,包括的种类很多。动物实验表明,环境内分泌干扰物具有拟/抗雌激素、拟/抗雄激素、拟/抗甲状腺激素等活性,其中有拟雌激素活性或抗雄激素活性的占大多数,能够造成发育期动物内分泌、生殖功能改变,可引起幼年动物的生殖毒性。青春期儿童处于发育期,其下丘脑_垂体_性腺轴对进入体内的环境内分泌干扰物很敏感,因此,环境内分泌干扰物可能是引起青春期性发育异常的一个重要因素,在女孩主要表现为性早熟,在男孩主要表现为青春期延迟。     

环境内分泌干扰物生殖毒性检测方法研究进展

环境内分泌干扰物分布广泛,严重威胁人体健康。过去几十年中,人类发现和合成了大量化合物,至今仍有许多化合物的生殖系统内分泌干扰效应不能明确。如何快速筛选识别环境内分泌干扰物并评估其生殖毒性,是需要重点关注的问题。本文对环境内分泌干扰物生殖毒性的筛选检测方法进行综述,总结其优势与局限性,为相关研究中方法选取提供参考。     

094 环境内分泌干扰物对青春期儿童性发育的影响

环境内分泌干扰物是环境中存在的一类化学物质，包括的种类很多。动物实验表明，环境内分泌干扰物具有拟，抗雌激素、拟，抗雄激素、拟，抗甲状腺激素等活性，其中有拟雌激素活性或抗雄激素活性的占大多数，能够造成发育期动物内分泌、生殖功能改变，可引起幼年动物的生殖毒性。青春期儿童处于发育期，其下丘脑一垂体一性腺轴对进入体内的环境内分泌干扰物很敏感，因此，环境内分泌干扰物可能是引起青春期性发育异常的一个重要因素，在女孩主要表现为性早熟，在男孩主要表现为青春期延迟。     

Estrogenic action of DDT analogs

The estrogenic action of DDT analogs, among these methoxychlor, is discussed. Emphasis is placed on investigations of estrogenic properties of DDT derivatives, their long-term effects on reproductive processes, and their mechanism of action. Kepone is discussed briefly as an example of another structural class of insecticides with estrogenic activity.     

Reproductive function in rats exposed prenatally to pesticides and polychlorinated biphenyls (PCB).

The pesticides methoxychlor, Kepone, dieldrin, aldrin, and the PCB's Aroclor 1221, 1242 and 1260 were fed to female rats during pregnancy in order to study reproductive function in the male and female offspring. Kepone alone produced significant reproductive aberrations. At 6 months of age the female offspring of Kepone-treated dams exhibited persistent vaginal estrus (PVE), anovulation, and tonic levels of serum estradiol. Other substances, such as methoxychlor and Aroclor 1221, previously shown to be estrogenic were not effective in altering reproductive function in the male or female offspring. The reproductive aberrations following Kepone exposure are thought to be due to alteration of hypothalamic differentiation during perinatal development.     

Effects of endocrine-disrupting contaminants on amphibian oogenesis: methoxychlor inhibits progesterone-induced maturation of Xenopus laevis oocytes in vitro

There is currently little evidence of pollution-induced endocrine dysfunction in amphibia, in spite of widespread concern over global declines in this ecologically diverse group. Data regarding the potential effects of endocrine-disrupting contaminants (EDCs) on reproductive function in amphibia are particularly lacking. We hypothesized that estrogenic EDCs may disrupt progesterone-induced oocyte maturation in the adult amphibian ovary, and tested this with an in vitro germinal vesicle breakdown assay using defolliculated oocytes from the African clawed frog, Xenopus laevis. While a variety of natural and synthetic estrogens and xenoestrogens were inactive in this system, the proestrogenic pesticide methoxychlor was a surprisingly potent inhibitor of progesterone-induced oocyte maturation (median inhibitive concentration, 72 nM). This inhibitory activity was specific to methoxychlor, rather than to its estrogenic contaminants or metabolites, and was not antagonized by the estrogen receptor antagonist ICI 182,780, suggesting that this activity is not estrogenic per se. The inhibitory activity of methoxychlor was dose dependent, reversible, and early acting. However, washout was unable to reverse the effect of short methoxychlor exposure, and methoxychlor did not competitively displace [3H]progesterone from a specific binding site in the oocyte plasma membrane. Therefore, methoxychlor may exert its action not directly at the site of progesterone action, but downstream on early events in maturational signaling, although the precise mechanism of action is unclear. The activity of methoxychlor in this system indicates that xenobiotics may exert endocrine-disrupting effects through interference with progestin-regulated processes and through mechanisms other than receptor antagonism.     

Interactive effects of p,p'-dichlorodiphenyldichloroethylene and methoxychlor on hormone synthesis in largemouth bass ovarian cultures

p,p'-Dichlorodiphenyldichloroethylene (DDE) and methoxychlor were tested alone and in combination to assess the similarity of their actions on hormone synthesis in gonadal tissue from largemouth bass (Micropterus salmoides floridanus), a species whose reproductive fitness has relevance to ecosystem health in Florida (USA). Gonads were harvested from adult female bass (age, two to three years) during the peak reproductive season (January-May), minced, and incubated in culture medium with or without test agents for 48 h. Duplicates of each treatment were performed in each of three experiments using tissue from a different female. Both 17beta-estradiol and testosterone were measured in aliquots of culture medium by validated radioimmunoassay procedures. Dose-response relationships of individual agents were characterized over a 6-log concentration range (1 X 10(-2) to 1 X 10(4) ppb). Both DDE and methoxychlor, tested individually, produced a dose-dependent decrease in testosterone levels. 17beta-Estradiol levels were unaffected. Mixtures of the agents were tested at all concentration combinations of 0.01, 1, 100, and 10,000 ppb in culture medium. Statistical tests indicated that of 16 dose combinations tested, 15 were antagonistic, and only 1 was additive based on the Loewe additivity model of no interaction. These results imply that methoxychlor and DDE inhibit testosterone production by different mechanisms in bass ovaries.     

Kisspeptin对下丘脑-垂体-卵巢轴的调控作用

Kisspeptin是调节女性生殖功能重要的神经肽,主要在下丘脑促性腺激素释放激素（gonadotropin-releasing hormone, GnRH）神经元的上游起作用,与GnRH神经元上的相应受体GPR54结合后刺激GnRH的释放,从而导致生殖轴后续一系列的活动。然而,近年来研究显示,Kisspeptin不仅...     

上皮-间质转化与女性生殖系统发育、功能及疾病

上皮-间质转化（epithelial-mesenchymal transition，EMT）是指上皮细胞在形态学上发生向成纤维细胞或间质细胞表型转化的过程，在胚胎发育、组织再生、肿瘤转移和器官纤维化疾病中发挥重要作用。随着EMT在生殖领域不断被发现，EMT作为女性生殖系统的重要调控机制越来越受到关注。本文综述了EMT在女性生殖系统形成、发育及正常功能中的重要性，并讨论EMT在病理状态如子宫内膜异位症、宫腔粘连和生殖系统恶性肿瘤等疾病发生中的作用，以期为女性生殖系统的研究及疾病治疗提供新思路。     

二(口恶)英类内分泌干扰物对胚胎的影响及其机制

环境污染随着工业的发达而日趋严重 ,对人类健康产生了严重的危害 ,导致肿瘤、免疫缺陷、神经毒效应等。尤其是类似雌激素作用的环境内分泌干扰物引起动物生殖变异、出生缺陷和威胁人类生殖健康 ,在最近几年里已引起人类学家的日趋重视。然而 ,内分泌干扰物的生殖毒性作用 ,对胚胎发育的影响及其可能的机制尚未完全明了。该文就二口恶英类化学物对胚胎的毒性作用及其机制进行综述。     

Effects of inhalation of ethylene oxide on female rats

The effects of systemic toxicity including reproductive toxicity of ethylene oxide on female rats were studied. When Wistar female rats were exposed to 250 ppm of ethylene oxide for six hours a day, five days a week for ten weeks, they showed inhibition of body weight gain and paralysis of the hindlegs. Hematological examination revealed macrocytic and normochromic anemia with high reticulocyte counts. The estrus cycle of the exposed group was prolonged and the percentage of the diestrus stage increased. There was no atrophy in the ovary or the uterus. However, the activity of glutathione reductase in the ovary decreased by 18% and that of glutathione-S-transferase increased by 30%. These results indicate that ethylene oxide has a similar effect on both female and male rats and that the female reproductive system is also affected.     

Modeling adverse environmental impacts on the reproductive system

When priority topics are being established for the study of women's health, it is generally agreed that one important area on which to focus research is reproduction. For example, increasing attention has been directed to environmental exposures that disrupt the endocrine system and alter reproduction. These concerns also suggest the need to give greater attention to the use of animal toxicologic testing to draw inferences about human reproductive risks. Successful reproduction requires multiple simultaneous and sequential processes in both the male and female, and the effect of toxicity on reproduction-related processes is time dependent. Currently, however, the risk assessment approach does not allow for the use of multiple processes or for considering the reproductive process response as a function of time. We discuss several issues in modeling exposure effects on reproductive function for risk assessment and present an overview of approaches for reproductive risk assessment. Recommendations are provided for an effective animal study design for determining reproductive risk that addresses optimization of the duration of dosing, observation of the effects of exposure on validated biomarkers, analysis of several biomarkers for complete characterization of the exposure on the underlying biologic processes, the need for longitudinally observed exposure effects, and a procedure for estimating human reproductive risk from the animal findings. An approach to characterizing reproductive toxicity to estimate the increased fertility risks in a dibromochloropropane (DBCP)-exposed human population is illustrated, using several reproductive biomarkers simultaneously from a longitudinal rabbit inhalation study of DBCP and an interspecies extrapolation method.