Endocrine Disruption and Cancer of Reproductive Tissues

Abstract A number of biological responses and multigenerational effects, mediated through the disruption of endocrine systems, have been observed in biota exposed to relatively low concentrations of environmental contaminants. These types of responses need to be considered within a weight of evidence approach in our risk assessment and risk management frameworks. However, including endocrine responses in an environmental risk assessment introduces a number of uncertainties that must be considered. A risk assessment of nonylphenol and nonylphenol polyethoxylates (NP/NPE) is used as a case study to demonstrate the sources and magnitude of some of the uncertainties associated with using endocrine disruption as an assessment endpoint. Even with this relatively well studied group of substances, there are substantial knowledge gaps which contribute to the overall uncertainties, limiting the interpretation within the risk assessment. The uncertainty of extrapolating from in vitro or biochemical responses to higher levels of organization or across species is not well understood. The endocrine system is very complex and chemicals can interact or interfere with the normal function of endocrine systems in a number of ways (e.g., receptors, hormones) which may or may not result in an adverse responses in the whole organism. Using endocrine responses can lead to different conclusions than traditional endpoints due to a variety of factors, such as differences in relative potencies of chemicals for specific endpoints (e.g., receptor binding versus chronic toxicity). The uncertainties can also be considerably larger and the desirability of using endocrine endpoints should be carefully evaluated. Endocrine disruption is a mode of action and not a functional endpoint and this needs to be considered carefully in the problem formulation stage and the interpretation of the weight of evidence.

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Influence of cellular metabolites on RNA and protein syntheses by Xanthium nuclei of different developmental phases

Canadian Journal of Botany ◽

10.1139/b86-386 ◽

1986 ◽

Vol 64 (12) ◽

pp. 2922-2927

Author(s):

A. Jana ◽

S. P. Sen

Keyword(s):

Rna Synthesis ◽

Supernatant Fraction ◽

Xanthium Strumarium ◽

Low Molecular Weight ◽

Transcriptional Level ◽

Protein Patterns ◽

Rna Molecules ◽

Reproductive Tissues ◽

Developmental Phases ◽

Vegetative Leaf

Leaf nuclei of vegetative and reproductive plants of Xanthium strumarium L. were incubated with the postribosomal supernatant of either phase and changes at the transcriptional level were studied in homologous and heterologous combinations. In the presence of the supernatant of reproductive plants, RNA synthesis by vegetative nuclei was decreased by 25%. Reproductive nuclei were less active in RNA synthesis. Gel electrophoretic studies revealed four RNA bands in vegetative nuclei incubated with reproductive supernatant, including a fast-moving low molecular weight band that could not be detected when the "vegetative" supernatant was used. The adenine/uracil ratios of the newly synthesized RNA of vegetative nuclei treated with vegetative and reproductive supernatants were 1.46 and 1.54, respectively, compared with 1.15 and 1.04 in the reproductive nuclei. Competitive DNA–RNA hybridization experiments indicated that about 2% of the [3H]RNA synthesized by nuclei of vegetative plants in the presence of the supernatant of reproductive plants could not be beaten out by the RNA of vegetative plants. Small quantitative differences, thus, may be expected in the RNA molecules synthesized by nuclei in the presence of the supernatant fraction of vegetative and reproductive plants. The supernatant fraction of the reproductive tissues decreased the incorporation of [3H]alanine and [3H]leucine in both the buffer-soluble and acid-soluble proteins and the nuclei of vegetative plants were more active in protein synthesis. Protein patterns as studied by acrylamide gel electrophoresis revealed alterations when vegetative leaf nuclei were incubated with the supernatant of reproductive tissues.

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Process Considerations for the Reduction of Endocrine Disruption Potential at Wastewater Treatment Facilities

Proceedings of the Water Environment Federation ◽

10.2175/193864701790860461 ◽

2001 ◽

Vol 2001 (11) ◽

pp. 652-674

Author(s):

R. David Holbrook ◽

John T. Novak ◽

Nancy G. Love ◽

Tom J. Grizzard

Keyword(s):

Wastewater Treatment ◽

Endocrine Disruption ◽

Treatment Facilities

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Metabolic-endocrine disruption due to preterm birth impacts growth, body composition, and neonatal outcome

Pediatric Research ◽

10.1038/s41390-021-01566-8 ◽

2021 ◽

Author(s):

Lea Sophie Möllers ◽

Efrah I. Yousuf ◽

Constanze Hamatschek ◽

Katherine M. Morrison ◽

Michael Hermanussen ◽

...

Keyword(s):

Body Composition ◽

Preterm Birth ◽

Postnatal Development ◽

Endocrine Disruption ◽

Fat Mass ◽

Neonatal Morbidity ◽

Neonatal Outcomes ◽

Endocrine Function ◽

List Type ◽

Term Infants

Abstract Despite optimized nutrition, preterm-born infants grow slowly and tend to over-accrete body fat. We hypothesize that the premature dissociation of the maternal–placental–fetal unit disrupts the maintenance of physiological endocrine function in the fetus, which has severe consequences for postnatal development. This review highlights the endocrine interactions of the maternal–placental–fetal unit and the early perinatal period in both preterm and term infants. We report on hormonal levels (including tissue, thyroid, adrenal, pancreatic, pituitary, and placental hormones) and nutritional supply and their impact on infant body composition. The data suggest that the premature dissociation of the maternal–placental–fetal unit leads to a clinical picture similar to panhypopituitarism. Further, we describe how the premature withdrawal of the maternal–placental unit, neonatal morbidities, and perinatal stress can cause differences in the levels of growth-promoting hormones, particularly insulin-like growth factors (IGF). In combination with the endocrine disruption that occurs following dissociation of the maternal–placental–fetal unit, the premature adaptation to the extrauterine environment leads to early and fast accretion of fat mass in an immature body. In addition, we report on interventional studies that have aimed to compensate for hormonal deficiencies in infants born preterm through IGF therapy, resulting in improved neonatal morbidity and growth. Impact Preterm birth prematurely dissociates the maternal–placental–fetal unit and disrupts the metabolic-endocrine maintenance of the immature fetus with serious consequences for growth, body composition, and neonatal outcomes. The preterm metabolic-endocrine disruption induces symptoms resembling anterior pituitary failure (panhypopituitarism) with low levels of IGF-1, excessive postnatal fat mass accretion, poor longitudinal growth, and failure to thrive. Appropriate gestational age-adapted nutrition alone seems insufficient for the achievement of optimal growth of preterm infants. Preliminary results from interventional studies show promising effects of early IGF-1 supplementation on postnatal development and neonatal outcomes.

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