A síndrome da disgenesia testicular e a hipótese do estrogênio: uma meta-análise quantitativa
| العنوان: | A síndrome da disgenesia testicular e a hipótese do estrogênio: uma meta-análise quantitativa |
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| المؤلفون: | Nikolaos Voulvoulis, Alan R. Boobis, Tassos Shialis, Mark D. Scrimshaw, Olwenn V. Martin, John N. Lester |
| المصدر: | Environmental Health Perspectives Scopus-Elsevier Ciência & Saúde Coletiva, Volume: 13, Issue: 5, Pages: 1601-1618, Published: OCT 2008 Ciência & Saúde Coletiva v.13 n.5 2008 Ciência & Saúde Coletiva Associação Brasileira de Saúde Coletiva (ABRASCO) instacron:ABRASCO |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Male, Estrogênio, Health, Toxicology and Mutagenesis, 05 Environmental Sciences, Diethylstilbestrol, Physiology, Estrogen receptor, TERM FOLLOW-UP, Review, Toxicology, testicular dysgenesis, Sex hormone-binding globulin, GERM-CELL CANCER, Cryptorchidism, Testis, estrogen, SDT, Public, Environmental & Occupational Health, oral contraceptives, Hypospadias, Health Policy, Environmental exposure, 11 Medical And Health Sciences, endocrine disruption, ENVIRONMENTAL SCIENCES, RECEPTOR-ALPHA GENE, testicular cancer, DIETHYLSTILBESTROL IN-UTERO, Meta-analysis, HUMAN FETAL TESTIS, Population study, Life Sciences & Biomedicine, cryptorchidism, environment, MALE REPRODUCTIVE HEALTH, medicine.drug, medicine.medical_specialty, Offspring, medicine.drug_class, Criptorquidismo, ENDOCRINE-DISRUPTING CHEMICALS, Environmental Sciences & Ecology, Hipospádias, Biology, Testicular cancer, Internal medicine, BIRTH-DEFECTS, medicine, Endocrine system, Humans, hypospadias, Pregnancy, Sexual differentiation, Science & Technology, Oral contraceptives, business.industry, Contraceptivos orais, Public Health, Environmental and Occupational Health, Estrogens, MATERNAL HORMONE-LEVELS, medicine.disease, DES, Estrogen, meta-analysis, Endocrinology, PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH, SCI, Etiology, biology.protein, RISK-FACTORS, diethylstilbestrol, Câncer de testículo, business |
| الوصف: | Impaired spermatogenesis, male reproductive tract abnormalities such as hypospadias and cryptorchidism, and testicular cancer have been proposed to comprise a common underlying syndrome with a common aetiology resulting from the disruption of embryonic programming and gonadal development during fetal life, termed the testicular dysgenesis syndrome (TDS) (Sharpe and Skakkebaek 2003; Skakkebaek et al. 2001). A hormonal etiology most likely underlies this syndrome, although it is believed to have more than one cause, possibly including other than endocrine disruption. Some common causes of endocrine disruption include infection, diet and body weight, lifestyle, genetics, and environmental exposure, but endocrine-disrupting chemicals (EDCs), particularly those with estrogen-like properties, have received the most scientific attention. The synthetic estrogenic drug diethylstilbestrol (DES) was prescribed to more than 5 million pregnant women from the late 1940s to the early 1970s to prevent abortions and pregnancy-related complications (Palmlund et al. 1993). Evidence later showed that maternal ingestion of DES during early pregnancy increased the risk of vaginal clear cell adenocarcinoma in female offspring (Herbst et al. 1971) and resulted in an increased incidence of malformations of the testes, the development of epididymal cysts, and impaired sperm quality in male offspring (Bibbo et al. 1977). During pregnancy, maternal estrogen levels are significantly elevated. However, more than 90% of maternal endogenous estrogens are effectively sequestered via binding to sex hormone binding globulin (SHBG), and thus the fetus is relatively protected (Joffe 2001; Vidaeff and Sever 2005). On the other hand, DES and ethinylestradiol do not bind well to SHBG, having a higher biopotency if ingested (Sharpe and Skakkebaek 2003; Vidaeff and Sever 2005). Additionally, transgenerational exposure is also possible when lipophilic xenoestrogens are mobilized during pregnancy and lactation (Colborn et al. 1993). Previous systematic reviews of studies in which pregnant women were exposed to estrogens other than DES have failed to find evidence of an increased risk of urogenital abnormalities in the male offspring (Raman-Wilms et al. 1995; Storgaard et al. 2006; Toppari et al. 1996; Vidaeff and Sever 2005), and have raised the possibility that nonestrogenic or atypical estrogenic effects of DES exposure in utero induce male reproductive abnormalities. However, none of the effects of DES exposure on either male or female offspring of exposed wild-type pregnant mice were induced when administered to ERKO (ER-α knockout) mice (Couse et al. 2001), strongly suggesting an ER-α–mediated mechanism. There is, however, a body of experimental data that is consistent with an effect of antiandrogenic industrial chemicals on male sexual differentiation (Gray et al. 1999, 2000). Moreover, mechanisms other than endocrine disruption may be involved in testicular toxicity; for example, the nematocide dibromochloropropane, an alkylating agent, is one of the most potent known testicular toxins in adults (Joffe 2001). In this review we focus on the estrogen hypothesis of TDS. Although several systematic reviews of the literature on the association between estrogenic agents and the disorders thought to belong to the TDS have been published, they are predominantly qualitative and the only quantitative summary estimate of the association between prenatal exposure to estrogenic agents and testicular cancer was published over 10 years ago (Toppari et al. 1996). The primary objective of a quantitative meta-analysis is to combine the results of previous studies examining a specific research question to arrive at a summary conclusion about a body of research. It has been found particularly useful when individual studies are too small to yield a valid conclusion, but it cannot, however, correct for bias and confounding. When applied to observational studies, subset analysis can be a useful tool to explore the reasons for discrepancies among the results of different studies. The objectives of this research were therefore to carry out a quantitative meta-analysis of the association between three of the end points related to TDS and prenatal exposure to estrogenic agents that would account for both the size and quality of the studies included and yield updated summary estimates in light of the body of research carried out since the formulation of the estrogen hypothesis. Inclusion in this analysis was based on mechanistic criteria, and the plausibility of an ER-α–mediated mode of action was specifically explored. Moreover, subset analysis has been applied to categories of compounds with estrogenic potencies differing by several orders of magnitude in an attempt to detect the existence of any potency–response trend. Most of the studies of sperm quantity or quality have been concerned with time trends rather than etiology, and this end point was not considered further here. |
| وصف الملف: | text/html |
| تدمد: | 1678-4561 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5963c5f486f4149ab679d27c25374535Test https://pubmed.ncbi.nlm.nih.gov/18288311Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5963c5f486f4149ab679d27c25374535 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16784561 |
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