Defective spermatogenesis: Martin et al. respond

This is an Open Access article - Copyright @ National Institute of Environmental Health Science.BACKGROUND: Male reproductive tract abnormalities such as hypospadias and cryptorchidism, and testicular cancer have been proposed to comprise a common syndrome together with impaired spermatogenesis with a common etiology resulting from the disruption of gonadal development during fetal life, the testicular dysgenesis syndrome (TDS). The hypothesis that in utero exposure to estrogenic agents could induce these disorders was first proposed in 1993. The only quantitative summary estimate of the association between prenatal exposure to estrogenic agents and testicular cancer was published over 10 years ago, and other systematic reviews of the association between estrogenic compounds, other than the potent pharmaceutical estrogen diethylstilbestrol (DES), and TDS end points have remained inconclusive. OBJECTIVES: We conducted a quantitative meta-analysis of the association between the end points related to TDS and prenatal exposure to estrogenic agents. Inclusion in this analysis was based on mechanistic criteria, and the plausibility of an estrogen receptor (ER)-α–mediated mode of action was specifically explored. RESULTS: We included in this meta-analysis eight studies investigating the etiology of hypospadias and/or cryptorchidism that had not been identified in previous systematic reviews. Four additional studies of pharmaceutical estrogens yielded a statistically significant updated summary estimate for testicular cancer. CONCLUSIONS: The doubling of the risk ratios for all three end points investigated after DES exposure is consistent with a shared etiology and the TDS hypothesis but does not constitute evidence of an estrogenic mode of action. Results of the subset analyses point to the existence of unidentified sources of heterogeneity between studies or within the study population

Testicular Dysgenesis Syndrome and the Estrogen Hypothesis: A Quantitative Meta-Analysis

BACKGROUND: Male reproductive tract abnormalities such as hypospadias and cryptorchidism, and testicular cancer have been proposed to comprise a common syndrome together with impaired spermatogenesis with a common etiology resulting from the disruption of gonadal development during fetal life, the testicular dysgenesis syndrome (TDS). The hypothesis that in utero exposure to estrogenic agents could induce these disorders was first proposed in 1993. The only quantitative summary estimate of the association between prenatal exposure to estrogenic agents and testicular cancer was published over 10 years ago, and other systematic reviews of the association between estrogenic compounds, other than the potent pharmaceutical estrogen diethylstilbestrol (DES), and TDS end points have remained inconclusive. OBJECTIVES: We conducted a quantitative meta-analysis of the association between the end points related to TDS and prenatal exposure to estrogenic agents. Inclusion in this analysis was based on mechanistic criteria, and the plausibility of an estrogen receptor (ER)-–mediated mode of action was specifically explored. RESULTS: We included in this meta-analysis eight studies investigating the etiology of hypospadias and/or cryptorchidism that had not been identified in previous systematic reviews. Four additional studies of pharmaceutical estrogens yielded a statistically significant updated summary estimate for testicular cancer. CONCLUSIONS: The doubling of the risk ratios for all three end points investigated after DES exposure is consistent with a shared etiology and the TDS hypothesis but does not constitute evidence of an estrogenic mode of action. Results of the subset analyses point to the existence of unidentified sources of heterogeneity between studies or within the study population

Ammonia damage costs. Final report

Ammonia (NH3) emissions, from agricultural and non-agricultural sources, have been associated with mainly two environment impacts - acidification and nutrient enrichment. As a source of nitrogen, ammonia can increase soil fertility and cause damage to ecosystems that exist because of naturally low levels of soil nitrogen. It can also contribute to the eutrophication of water bodies. Deposition of acidifying pollutants (including NOx and NH3) has a range of detrimental effects including: • Increased acidity of freshwaters which has led to the loss of fish and other organisms from many rivers and lakes; • Increased acidity of soils which alters soil chemistry and can leave forests and other terrestrial ecosystems vulnerable to drought, disease and insect attack; • Acidic groundwater which damage water supply infrastructure and increase the levels of harmful metals in drinking water; • Eutrophication (excess nutrient enrichment of natural ecosystems) from deposition of the nitrogen-containing atmospheric pollutants NOx and NH3; and • Ammonia emissions are also associated with secondary particulate formation (ammonium sulphates and ammonium nitrates) and thus have implications for human health and climate change. A new inventory for 2004 for ammonia emissions in the UK has been developed . The major sources for atmospheric ammonia in the UK are agricultural activities (in particular, livestock production) which account for over 85% of the total , followed by biomass burning (including forest fires) and to a lesser extent fossil fuel combustion. Objectives of the study The main aim of this study is to provide estimates of the external environmental and human health damage costs attributed to ammonia emissions from agricultural and non-agricultural sources. These estimates will feed into: • cost-benefit analysis of policies aimed at reducing ammonia emissions (a Defra funded project managed by IGER is currently developing an ammonia strategy), and; • the Environmental accounts for agriculture analysis being conducted by Defra (and managed by Jacobs Babtie). The study concentrated on environment impacts arising from ammonia emissions in three areas: • ecosystem; • human health, and; • climate change The outputs of this study will be utilised by the abovementioned projects and for this reason the managers of these projects were contacted in the early stages of this study to get their views on how this study can provide useful outputs for their projects. With regards to the Ammonia strategy project it was mentioned that any costs on ammonia emissions would be useful to feed into the cost-benefit analysis that will be undertaken. However the Environmental accounts suggested that more specific outputs would be useful for their analysis e.g. ideally studies that value environmental impacts using a dose response method, primarily from agricultural emissions. Their feedback was taken into consideration and was addressed, where possible, in the outputs of this study

Testicular dysgenesis syndrome and the estrogen hypothesis: a quantitative meta-analysis A síndrome da disgenesia testicular e a hipótese do estrogênio: uma meta-análise quantitativa

Male reproductive tract abnormalities such as hypospadias and cryptorchidism, and testicular cancer have been proposed to comprise a common syndrome together with impaired spermatogenesis with a common etiology resulting from the disruption of gonadal development during fetal life, the testicular dysgenesis syndrome (TDS). The only quantitative summary estimate of the link between prenatal exposure to estrogenic agents and testicular cancer was published over 10 years ago; other reviews of the link between estrogenic compounds, other than the potent pharmaceutical estrogen diethylstilbestrol (DES), and TDS end points have remained inconclusive. We conducted a quantitative meta-analysis of the association between the end points related to TDS and prenatal exposure to estrogenic agents. Inclusion in this analysis was based on mechanistic criteria, and the plausibility of an estrogen receptor (ER)-&#945;-mediated mode of action was specifically explored. Eight studies were included, investigating the etiology of hypospadias and/or cryptorchidism that had not been identified in previous systematic reviews. Four additional studies of pharmaceutical estrogens yielded a statistically significant updated summary estimate for testicular cancer. Results of the subset analyses point to the existence of unidentified sources of heterogeneity between studies or within the study population.<br>Sugeriu-se que anomalias do trato reprodutivo masculino como hipospádia e criptorquidismo, assim como o câncer de testículo, componham uma síndrome comum com diminuição da espermatogênese, e de etiologia comum, a interrupção do desenvolvimento gonadal na fase fetal, a síndrome de disgenesia testicular (SDT). O único levantamento quantitativo da relação entre exposição pré-natal a agentes estrogênicos e câncer de testículo data de mais de dez anos; outras revisões da relação entre compostos estrogênicos diferentes do potente estrogênio sintético dietilstilbestrol (DES) e SDT continuam inconclusivas. Foi feita uma meta-análise quantitativa da relação entre SDT e exposição pré-natal a agentes estrogênicos. A inclusão na análise baseou-se em critérios mecanísticos e foi explorada a plausibilidade de um modo de ação mediada pelo receptor estrogênico-&#945; (RE&#945;). Incluíram-se oito estudos sobre a etiologia das hipospádias e/ou criptorquidismo não identificados em revisões sistemáticas anteriores. Mais quatro estudos sobre estrogênios sintéticos resultaram em uma estimativa estatisticamente significativa para câncer de testículo. Os resultados das análises dos subconjuntos apontam à existência de fontes não identificadas de heterogeneidade entre estudos ou populações estudadas