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译作分享|环境内分泌干扰物对青春期发育的影响（上）

2023年02月06日

译作分享

Effects of Environmental Endocrine Disruptors on Pubertal Development

环境内分泌干扰物对青春期发育的影响

Samim Özen¹, fiükran Darcan²

¹Pediatric Endocrinology Unit, Mersin Children Hospital, Mersin, Turkey

²Department of Pediatric Endocrinology and Metabolism, Ege University School of Medicine, Izmir, Turkey

ABSTRACT/摘要

The onset and course of puberty are under the control of the neuroendocrine system. Factors affecting the timing and regulation of the functions of this system may alter the onset and course of puberty. Several environmental endocrine disruptors (EDs) with significant influences on the normal course of puberty have been identified. Numerous animal and human studies concerning EDs have been conducted showing that these substances may extensively affect human health; nevertheless, there are still several issues that remain to be clarified. In this paper, the available evidence from animal and human studies on the effects of environmental EDs with the potential to cause precocious or delayed puberty was reviewed.

青春期的开始和过程由神经内分泌系统控制。影响该系统功能的时间和调节的因素可能改变青春期的开始和过程。一些对青春期正常进程有重大影响的环境内分泌干扰物（EDs）已经被确认。有关EDs的许多动物和人类研究表明，这些物质可能广泛影响人类健康；然而，仍有一些问题有待澄清。本文综述了动物和人类研究的现有证据，这些证据表明环境中的EDs有可能造成性早熟或青春期延迟。

Introduction/导言

Recent studies have demonstrated a progressive decrease in age of onset of puberty in children around the world. Although the exact reason for this shift is not completely understood, it is generally accepted to be the outcome of a complex interaction between genetic, endocrine and environmental factors. It is also known that owing to the acceleration of industrialization throughout the world, a gradual but significant increase has occurred in the number and amount of environmental pollutants. Some of these environmental pollutants are natural or synthetic chemicals with considerable effects on the endocrine system. The chemicals that have negative effects on the endocrine system are called endocrine disruptors (EDs). EDs exert their effects through different mechanisms: by binding to the relevant hormone receptors; by direct action on cell signaling pathways or on the central nervous system and the neuroendocrine system; by suppression of hormone synthesis; or through their toxic effects on the relevant organs. Several EDs such as phytoestrogens, topical and natural estrogens, pesticides, industrial chemicals and phthalates have been identified as possible agents affecting pubertal development in humans. The potential of EDs to cause precocious puberty has first been noticed in the early 1990s. Afterwards, the effects of EDs on the onset and course of puberty have been demonstrated in numerous animal and human studies and, subsequently, the use of some of these chemicals has even been prohibited. This paper aims to review the present information regarding environmental EDs that may negatively affect pubertal development.

最近的研究表明，世界各地的儿童青春期开始的年龄在逐渐下降。虽然这种转变的确切原因还不完全清楚，但人们普遍认为这是遗传、内分泌和环境因素之间复杂的相互作用的结果。众所周知，由于全世界各地工业化进程的加速，环境污染物的数量和种类在逐渐但显著的增加。其中一些环境污染物是天然或合成化学品，对内分泌系统有相当大的影响。对内分泌系统有负面影响的化学物质被称为内分泌干扰物（EDs）。EDs通过不同的机制发挥作用：通过与相关激素受体结合；通过对细胞信号通路或中枢神经系统和神经内分泌系统直接作用；通过抑制激素合成；或通过它们对相关器官产生的毒性作用。植物雌激素、外用和天然雌激素、杀虫剂、工业化学品和邻苯二甲酸盐等几种EDs已被确定为影响人类青春期发育的可能因素。ED导致性早熟的可能性在1990年代初首次被注意到。之后，EDs对青春期开始和过程的影响已在许多动物和人类研究中得到证实，随后，其中某些化学物甚至被禁止使用。本文旨在回顾目前可能对青春期发育产生负面影响的环境Eds的信息。

The Effects of Endocrine Disruptors on Puberty

内分泌干扰物对青春期的影响

Recent studies have demonstrated that age of onset of puberty has shifted to younger ages by about 1 or 2 years, while no change has been noted in the age of menarche. The triggering mechanism for the earlier onset of puberty is not clearly understood. It is thought to occur as a result of a complex interaction between genetic, hormonal and environmental factors. Recently, ED chemicals have been intensively accused of being potential hazardous environmental factors (1,2,3,4,5,6).

最近的研究表明，青春期的开始已经提早到更小的年龄，大约1或2年，而月经初潮的年龄没有变化。青春期提早开始的触发机制尚不清楚。它被认为是遗传、荷尔蒙和环境因素之间复杂的相互作用的结果。最近，ED化学品被强烈指责为潜在的有害环境因素（1,2,3,4,5,6）。

EDs are environmental chemicals, which may either be natural or synthetic. Some of the major EDs are presented in Table 1. EDs accumulate in the environment in the long term and are introduced into the human body through water, air, foodstuffs, or through equipments used in the office and home. Additionally, it has been demonstrated that EDs can be transferred from the mother to the fetus via placenta or to the baby via breast milk (1,2,3,4,5).

EDs是环境化学品，可能是天然或合成的。一些主要的Eds列于表1。Eds在环境中长期积累，并通过水、空气、食品或办公室和家庭使用的设备进入人体。此外，已经证明，EDs可以通过胎盘从母亲转移到胎儿，或通过母乳转移到婴儿身上（1,2,3,4,5）。

表1. 主要内分泌干扰物
植物雌激素	大豆苷元、染料木黄酮、福莫诺丁、生物香素-A、普鲁内汀、普拉坦赛因、黄豆素、雌马酚、地米替兰戈勒斯汀、肠内酯、肠二醇、马泰树脂醇、玉米赤霉烯酮
有机卤化物	二恶英、呋喃、多氯联苯、六氯苯、五氯苯酚
杀虫剂	二氯二苯基三氯乙烷（ DDT）、甲氧基氯、硫丹、2，4-二氯苯氧乙酸、甲草胺、涕灭威、氨薇醇、阿特拉津、苯甲酰基、二溴氯丙烷、西维因、氯丹、乙基对硫磷、七氯、开蓬酮、酮康唑、林丹、甲氧乙酯、氯菊酯、马拉硫磷、三氟乐灵、长春唑林
邻苯二甲酸盐	邻苯二甲酸二乙基己酯、丁苄酯、邻苯二甲酸酯、邻苯二甲酸二正丁酯、邻苯二甲酸二己酯、邻苯二甲酸二丙酯、邻苯二甲酸二氯己酯、邻苯二甲酸二乙酯
重金属	砷、镉、铀、铅、汞
药物	口服避孕药、己烯雌酚、西咪替丁
工业产品	双酚A、多溴联苯

Due to their hormone-like characteristics, EDs mostly affect the endocrine system in an agonist- or antagonist-specific manner and can be classified according to their mechanisms of action. They influence puberty through their estrogenic, antiestrogenic, androgenic, antiandrogenic effects or through their direct effects on the gonadotropin-releasing hormone (GnRH). These chemicals may exert their estrogenic effects either directly by binding to estrogen receptors, increasing aromatase activity and increasing estrogen sensitivity or indirectly by their effect on GnRH, leading to an increase in endogenous estrogen production. All of these effects may result in precocious puberty. EDs produce antiestrogenic and androgenic effects through inhibition of aromatase enzyme activity and steroidogenic enzyme production. They display antiandrogenic effects via suppression of testicular steroidogenesis and androgen-receptor blockade. Thus, depending on their mechanism of action, EDs may lead to precocious puberty, to delayed puberty, or to sexual differentiation disorders (1,4,5,6,7,8,9,10,11). Classification of some of the EDs according to their mechanism of action is presented in Table 2.

由于其激素样特征，EDs大多以激动剂或拮抗剂特异性方式影响内分泌系统，并可以根据其作用机制进行分类。它们通过雌激素、抗雌激素、雄激素、抗雄激素作用或对促性腺激素释放激素（GnRH）的直接作用影响青春期。这些化学品可能直接通过与雌激素受体结合、增加芳香化酶活性和增加雌激素敏感性来发挥雌激素作用，或间接通过对GnRH的影响使内源性雌激素分泌增加，从而发挥其雌激素的作用。所有这些影响都可能导致性早熟的发生。EDs通过抑制芳香化酶活性和类固醇酶的产生而产生抗雌激素和雄激素作用。EDs通过抑制睾丸类固醇生成和阻断雄激素受体显示出抗雄激素的作用。因此，根据其作用机制，EDs可能导致性早熟、延迟青春期或性分化障碍（1,4,5,6,7,8,9,10,11）。表2根据EDs的作用机制进行了分类。

表2. 根据所列内分泌干扰物的作用机制对其进行分类
雌激素作用	二苯基二氯乙烷（DDT）及其代谢产物甲氧基氯甲基苯丙胺植物雌激素（高浓度）多氯联苯双酚A 硫丹二恶英
抗雌激素作用	植物性雌激素（低浓度）
雄激素作用	睾酮群勃龙醋酸酯
抗雄激素作用	邻苯二甲酸酯二氯二苯基三氯乙烷（DDT）长春唑林

Natural Endocrine Disruptors

天然内分泌干扰物

The best known chemicals in this group are phytoestrogens, which are relatively weak compared to endogenous estrogen. They are found in several nutrients that are frequently consumed in daily life (i.e. carrots, garlic, apple, coffee, cherry, parsley, legumes). Phytoestrogens have estrogenic effects when consumed in huge amounts and antiestrogenic effects at low concentrations (4,7,8).

该组中最著名的化学物质是植物雌激素，与内源性雌激素相比，植物雌激素的作用相对较弱。它们存在于日常生活中经常食用的几种营养物质中（即胡萝卜、大蒜、苹果、咖啡、樱桃、欧芹、豆类）。大量食用植物雌激素时具有雌激素作用，而在低浓度时具有抗雌激素作用（4,7,8）。

Synthetic Endocrine Disruptors

合成内分泌干扰物

Diethylstilbestrol (DES) is the best known ED with strong estrogenic activity. It was first synthesized in 1938 and has since been widely used worldwide for medical indications including pregnancy toxemia and preterm labor. However, a twofold increase in breast cancer incidence was observed in mothers exposed to DES. It was also shown that the incidence of cervical cancer, ovarian germ cell cancer, cervical or vaginal dysplasia, and vaginal clear-cell adenocarcinoma was increased in female infants born to mothers exposed to DES (12). The production or marketing of this chemical is prohibited since 1997.

己烯雌酚，Diethylstilbestrol（DES）是最著名的具有强烈雌激素活性的ED。它于1938年首次合成，此后在全球范围内广泛用于医学适应症，包括妊娠毒血症和早产。然而，在暴露于DES的母亲中，观察到乳腺癌的发病率增加了2倍。研究还显示，暴露于DES的母亲所生的女婴中，宫颈癌、卵巢生殖细胞癌、宫颈或阴道发育不良以及阴道透明细胞腺癌的发病率有所增加（12）。自1997年以来，这种化学品已被禁止生产或销售。

Many chemicals including pesticides, fungicides, herbicides used in agriculture, cleaning substances used in daily life, contents of cosmetic products, dyes, plastic substances and solvents are likely to be EDs. As neutralization or inactivation is difficult and most of these substances often accumulate in fat tissue, they may persist in the body for long periods of time and cause harmful effects (4,5,6,7,8,9,10,11).Time of exposure to EDs is important in terms of their detrimental effects. Male rodents exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in intrauterine life were found to experience problems in masculinization of internal and external genitalia, descent of testicles, androgen production and in spermatogenesis. On the other hand, it was observed that postnatal exposure to TCDD was associated only with impairment of spermatogenesis and somatic and genital growth. The dose and duration of exposure to EDs is also important in terms of potential negative consequences. The negative effects may become more serious as the duration of exposure and dose increase (1,11,13).

许多化学品，包括农业中使用的杀虫剂、杀菌剂、除草剂、日常生活中使用的清洁物质、化妆品的内容物、染料、塑料物质和溶剂都可能是Eds。由于中和或灭活很困难，而且大多数这些物质通常积累在脂肪组织中，它们可能会在体内长期存在并造成有害影响（4,5,6,7,8,9,10,11）。就其有害影响而言，接触EDs的时间长短很重要。在宫内生活中接触2,3,7,8-四氯二苯并对二恶英（TCDD）的雄性啮齿动物在内外生殖器男性化、睾丸下降、雄激素产生和精子发生方面出现问题。另一方面，据观察，产后接触TCDD仅与精子生成以及躯体和生殖器生长受损有关。就潜在的负面后果而言，接触EDs的剂量和持续时间也很重要。随着暴露持续时间和剂量的增加，负面影响可能会发展得更加严重（1,11,13）。

EDs do not necessarily lead to similar effects in all situations. For example, phytoestrogens have estrogenic effects in high doses, while they exert antiestrogenic effects in low doses (1,7).

EDs不一定在所有情况下都会导致类似的影响。例如，植物雌激素在高剂量下具有雌激素作用，而在低剂量下则发挥抗雌激素作用（1,7）。

Studies on Role of EDs in Precocious Puberty

关于EDs在性早熟中的作用研究

Several animal and human studies have been conducted investigating the role of EDs in precocious puberty. EDs may cause early puberty via their estrogenic or antiandrogenic effects and also by increasing GnRH production (1,4,5,6,7,8,9,10,11).

已经进行了几项动物和人类研究，调查EDs在性早熟中的作用。EDs可能通过其雌激素或抗雄激素作用及增加GnRH的分泌而引起青春期提前（1,4,5,6,7,8,9,10,11）。

未完待续。。。。

参考文献

1. Buck Louis GM, Gray LE Jr, Marcus M, Ojeda SR,Pescovitz OH, Witchel SF, Sippell W, Abbott DH, Soto A, Tyl RW, Bourguignon JP, Skakkebaek NE, Swan SH, Golub MS, Wabitsch M, Toppari J, Euling SY. Environmental factors and puberty timing: expert panel research needs. Pediatrics 2008;121:192-207. [Abstract] / [Full Text] / [PDF]

2. McLachlan JA, Simpson E, Martin M. Endocrine disrupters and female reproductive health. Best Pract Res Clin Endocrinol Metab 2006;20:63-75. [Abstract] / [Full Text] / [PDF]

3. Schoeters G, Den Hond E, Dhooge W, van Larebeke N,Leijs M. Endocrine disruptors and abnormalities of pubertal development. Basic Clin Pharmacol Toxicol 2008;102:168-175. [Abstract] / [Full Text] / [PDF]

4. Nebesio TD, Pescovitz OH. The role of endocrine disruptorsin pubertal development. In: Pescovitz OH, Walvoord EC (eds). When puberty is precocious: scientific and clinical aspects. New Jersey, Humanapress 2007;425-442.

5. Jacobson-Dickman E, Lee MM. The influence of endocrinedisruptors on pubertal timing. Curr Opin Endocrinol Diabetes Obes 2009;16:25-30. [Abstract]

6. Den Hond E, Schoeters G. Endocrine disrupters and human Q puberty. Int J Androl 2006;29:264-271. [Abstract] / [Full Text] / [PDF]

7. Roy JR, Chakraborty S, Chakraborty TR. Estrogen-likeendocrine disrupting chemicals affecting puberty in humans-a review. Med Sci Monit 2009;15:137-145.[Abstract]

8. Massart F, Parrino R, Seppia P, Federico G, Saggese G.How do environmental estrogen disruptors induce precocious puberty? Minerva Pediatr 2006;58:247-254.[Abstract]

9. Ediz Y. Endokrin bozucular. Güncel Pediatri 2008;6:76-82.[Abstract] / [Full Text] / [PDF]

10. Abaci A, Demir K, Bober E, Buyukgebiz A. Endocrine disruptors-with special emphasis on sexual development. Pediatric Endocrinol Rev 2009;6:464-475. [Abstract]

11. Diamanti-Kandarakis E, Bourguignon JP, Giudice LC,Hauser R, Prins GS, Soto AM, Zoeller RT, Gore AC. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev 2009;30:293-342. [Abstract] / [Full Text]

12. Giusti RM, Iwamoto K, Hatch EE. Diethylstilbestrol revisited: a review of the long-term health effects. Ann Intern Med 1995;122:778-788. [Abstract]

13. Ishihara K, Warita K, Tanida T, Sugawara T, Kitagawa H,Hoshi N. Does paternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affect the sex ratio of offspring? J Vet Med Sci 2007;69:347-352. [Full Text] / [PDF]

14. Semenza JC, Tolbert PE, Rubin CH, Guillette LJ Jr, JacksonRJ. Reproductive toxins and alligator abnormalities at Lake Apopka, Florida. Environ Health Perspect 1997;105:1030-1032. [Abstract] / [PDF]

15. Gray LE Jr, Ostby J, Ferrell J, Rehnberg G, Linder R,Cooper R, Goldman J, Slott V, Laskey J. A dose-response analysis of methoxychlor-induced alterations of reproductive development and function in the rat. Fundam Appl Toxicol 1989;12:92-108. [Abstract]

16. Honma S, Suzuki A, Buchanan DL, Katsu Y, Watanabe H,Iguchi T. Low dose effect of in utero exposure to bisphenol A and diethylstilbestrol on female mouse reproduction. Reprod Toxicol 2002;16:117-122. [Abstract] / [Full Text] /[PDF]

17. Nikaido Y, Yoshizawa K, Danbara N, Tsujita-Kyutoku M, YuriT, Uehara N, Tsubura A. Effects of maternal xenoestrogen exposure on development of the reproductive tract and mammary gland in female CD-1 mouse offspring. Reprod Toxicol 2004;18:803-811. [Abstract]

18. Markey CM, Luque EH, Munoz De Toro M, SonnenscheinC, Soto AM. In utero exposure to bisphenol A alters the development and tissue organization of the mouse mammary gland. Biol Reprod 2001;65:1215-1223. [Abstract]/ [Full Text] / [PDF]

19. Ashby J, Lefevre PA. The peripubertal male rat assay as an alternative to the Hershberger castrated male rat assay for the detection of anti-androgens, oestrogens and metabolic modulators. J Appl Toxicol 2000;20:35-47. [Abstract] / [PDF]

20. Roman BL, Peterson RE. In utero and lactational exposure of the male rat to 2,3,7,8-tetrachlorodibenzo-pdioxin impairs prostate development. 1. Effects on gene expression. Toxicol Appl Pharmacol 1998;150:240-253. [Abstract]

21. Gray LE, Wolf C, Mann P, Ostby JS. In utero exposure tolow doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin alters reproductive development of female Long Evans hooded rat offspring. Toxicol Appl Pharmacol 1997;146:237-244. [Abstract] / [Full Text]

22. Gray LE, Ostby JS, Kelce WR. A dose-response analysis ofthe reproductive effects of a single gestational dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin in male Long Evans Hooded rat offspring. Toxicol Appl Pharmacol 1997;146:11-20. [Abstract] / [PDF]

23. Stoker TE, Laws SC, Guidici DL, Cooper RL. The effect ofatrazine on puberty in male wistar rats: an evaluation in the protocol for the assessment of pubertal development and thyroid function. Toxicol Sci 2000;58:50-59. [Abstract] / [Full Text] / [PDF]

24. Laws SC, Ferrell JM, Stoker TE, Schmid J, Cooper RL. Theeffects of atrazine on female wistar rats: an evaluation of the protocol for assessing pubertal development and thyroid function. Toxicol Sci 2000;58:366-376. [Abstract] / [Full Text] / [PDF]

25. Fraites MJ, Cooper RL, Buckalew A, Jayaraman S, Mills L,Laws SC. Characterization of the hypothalamicpituitary-adrenal axis response to atrazine and metabolites in the female rat. Toxicol Sci 2009;112:88-99. [Abstract] / [Full Text] / [PDF]

26. Rubin BS, Lenkowski JR, Schaeberle CM, Vandenberg LN,Ronsheim PM, Soto AM. Evidence of altered brain sexual differentiation in mice exposed perinatally to low, environmentally relevant levels of bisphenol A. Endocrinology 2006;147:3681-3691.[Abstract] / [Full Text] /[PDF]

27. Howdeshell KL, Hotchkiss AK, Thayer KA, Vandenberg JG,vom Saal FS. Exposure to Bisphenol A advances puberty.Nature 1999;401:763-764. [Full Text]

28. Marty MS, Crissman JW, Carney EW. Evaluation of the EDSTAC female pubertal assay in CD rats using 17 beta-estradiol, steroid biosynthesis inhibitors, and a thyroid inhibitor, and a thyroid inhibitor. Toxicol Sci 1999;52:269-277. [Abstract] / [PDF]

29. Blystone CR, Furr J, Lambright CS, Howdeshell KL, RyanBC, Wilson VS, Leblanc GA, Gray LE Jr. Prochloraz inhibits testosterone production at dosages below those that affect androgen-dependent organ weights or the onset of puberty in the male Sprague Dawley rat. Toxicol Sci 2007;97:65-74. [Abstract] / [Full Text] / [PDF]

30. Laier P, Metzdorff SB, Borch J, Hagen ML, Hass U,Christiansen S, Axelstad M, Kledal T, Dalgaard M, McKinnell C, Brokken LJ, Vinggaard AM. Mechanisms of action underlying the antiandrogenic effects of the fungicide prochloraz. Toxicol Appl Pharmacol 2006;213:160-171. [Abstract] / [Full Text] / [PDF]

31. Blanck HM, Marcus M, Tolbert PE, Rubin C, Henderson AK,Hertzberg VS, Zhang RH, Cameron L. Age at menarche and tanner stage in girls exposed in utero and postnatally to polybrominated biphenyl. Epidemiology 2000;11:641-647. [Abstract] / [Full Text] / [PDF]

32. Blanck HM, Marcus M, Hertzberg V, Tolbert PE, Rubin C,Henderson AK, Zhang RH. Determinants of polybrominated biphenyl serum decay among women in the Michigan PBB cohort. Environ Health Perspect 2000;108:147-152. [Abstract] / [PDF]

33. Gladen BC, Ragan NB, Rogan WJ. Pubertal growth and development and prenatal and lactational exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene. J Pediatr 2000;136:490-496. [Abstract] / [Full Text] / [PDF]

34. Vasiliu O, Muttineni J, Karmaus W. In utero exposure toorganochlorines and age at menarche. Hum Reprod 2004;19:1506-1512. [Abstract] / [Full Text] / [PDF]

35. Krstevska-Konstantinova M, Charlier C, Craen M, Du Caju M,Heinrichs C, de Beaufort C, Plomteux G, Bourguignon JP. Sexual precocity after immigration from developing countries to Belgium: evidence of previous exposure to organochlorine pesticides. Hum Reprod 2001;16:1020-1026. [Abstract] / [Full Text] / [PDF]

36. Ouyang F, Perry MJ, Venners SA, Chen C, Wang B, YangF, Fang Z, Zang T, Wang L, Xu X, Wang X. Serum DDT, age at menarche, and abnormal menstrual cycle length. Occup Environ Med 2005;62:878-884. [Abstract] / [PDF]

37. Gray LE Jr, Ostby J, Cooper RL, Kelce WR. The estrogenicand antiandrogenic pesticide methoxychlor alters the reproductive tract and behavior without affecting pituitary size or LH and prolactin secretion in male rats. Toxicol Ind Health 1999;15:37-47. [Abstract] / [PDF]

38. Golub MS, Hogrefe CE, Germann SL, Lasley BL, NatarajanK, Tarantal AF. Effects of exogenous estrogenic agents on pubertal growth and reproductive system maturation in female rhesus monkeys. Toxicol Sci 2003;74:103-113. [Abstract] / [Full Text] / [PDF]

39. Masutomi N, Shibutani M, Takagi H, Uneyama C, TakahashiN, Hirose M. Impact of dietary exposure to methoxychlor, genistein, or diisononyl phthalate during the perinatal period on the development of the rat endocrine/ reproductive systems in later life. Toxicology 2003;192:149-170. [Abstract] / [Full Text] / [PDF]

40. Wade MG, Desaulniers D, Leingartner K, Foster WG.Interaction between endosulfan and dieldrin on estrogen-mediated processes in vitro and in vivo. Reprod Toxicol 1997;11:791-798. [Abstract]

41. Singh SK, Pandley RS. Effect of sub-chronic endosulfanexposures on plasma gonadotrophins, testosterone, testicular testosterone and enzymes of androgen biosynthesis in rat. Indian J Exp Biol 1990;28:953-956. [Abstract]

42. Andersen HR Wohlfahrt-Veje CV, Jensen TK, Grandjean P,Skakkebaek NE, Katharina M. Prenatal pesticide exposure is associated with long term effects on endocrine function in children. Poster presentation at Prenatal Programming and Toxicity. Miami Beach, Florida,2009;7-10.

43. Blystone CR, Lambright CS, Cardon MC, Furr J, Rider CV,Hartig PC, Wilson VS, Gray LE Jr. Cumulative and antagonistic effects of a mixture of the antiandrogens vinclozolin and iprodione in the pubertal male rat. Toxicol Sci 2009;111:179-188.[Abstract] / [Full Text] / [PDF]

44. Khurana S, Ranmal S, Ben-Jonathan N. Exposure of newborn male and female rats to environmental estrogens: delayed and sustained hyperprolactinemia and alterations in estrogen receptor expression. Endocrinology 2000;141: 4512-4517. [Abstract] / [PDF]

45. Yang CY, Yu ML, Guo HR, Lai TJ, Hsu CC, Lambert G, GuoYL. The endocrine and reproductive function of the female Yucheng adolescents prenatally exposed to PCBs/PCDFs.Chemosphere 2005;61:355-360. [Abstract] / [Full Text] / [PDF]

46. Denham M, Schell LM, Deane G, Gallo MV, Ravenscroft J,DeCaprio AP; Akwesasne Task Force on the Environment. Relationship of lead, mercury, mirex, dichlorodiphenyldichloroethylene, hexachlorobenzene, and polychlorinated biphenyls to timing of menarche among Akwesasne Mohawk girls. Pediatrics 2005;115:127-134.[Abstract] / [PDF]

47. Den Hond E, Roels HA, Hoppenbrouwers K, Nawrot T,Thijs L, Vandermeulen C, Winneke G, Vanderschueren D, Staessen JA. Sexual maturation in relation to polychlorinated aromatic hydrocarbons: Sharpe and Skakkebaek's hypothesis revisited. Environ Health Perspect 2002;110:771-776. [Full Text] / [PDF]

48. Warner M, Samuels S, Mocarelli P, Gerthoux PM,Needham L, Patterson DG Jr, Eskenazi B. Serum dioxin concentrations and age at menarche. Environ Health Perspect 2004;112:1289-1292. [Abstract] / [Full Text] / [PDF]

49. Colón I, Caro D, Bourdony CJ, Rosario O. Identification ofphthalate esters in the serum of young Puerto Rican girls with premature breast development. Environ Health Perspect 2000;108:895-900. [Abstract] / [PDF]

50. Wu T, Buck GM, Mendola P. Blood lead levels and sexualmaturation in US girls: The Third National Health and Nutrition Examination Survey, 1988-1994. Environ Health Perpect 2003;111:737-741. [Full Text] / [PDF]

51. Selevan SG, Rice DC, Hogan KA, Euling SY, Pfahles-Hutchens A, Bethel J. Blood lead concentration and delayed puberty in girls. N Engl J Med 2003;348: 1527-1536. [Abstract] / [FullText] /[PDF]

52. Soto AM, Vandenberg LN, Maffini MV, Sonnenschein C.Does breast cancer start in the womb? Basic Clin Pharmacol Toxicol 2008;102:125-133. [Abstract] / [Full Text] /[PDF]

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