Prenatal and childhood exposure to EDCs may be responsible for a variety of abnormalities in human sexuality, gender development and behaviors, reproductive capabilities, and sex ratios
Although scientists have postulated a wide range of adverse human health effects of exposure to endocrine-disrupting chemicals (EDCs), the nexus of the debate is the concern that prenatal and childhood exposure to EDCs may be responsible for a variety of abnormalities in human sexuality, gender development and behaviors, reproductive capabilities, and sex ratios. Scientists today are asking hard questions about potential human effects: Do EDC exposures impair fertility in men or women? Can they cause sexual organ malformations, stunted reproductive development, or testicular or breast cancer? Do fetal exposures to EDCs alter sex phenotypes? Do they change later gender-related neurobiological characteristics and behaviors such as play activity and spatial ability? Could such exposures even be involved in the etiology of children born with ambiguous gender?
EDCs include a spectrum of substances that can be loosely classified according to their known or suspected activity in relation to sex hormone receptors and pathways. The most-studied and best known are the environmental estrogens, which mimic estradiol and bind to estrogen receptors (ERs). ER agonists include the pesticide methoxychlor, certain polychlorinated biphenyls (PCBs), bisphenol A (BPA; a high production volume chemical used to make polycarbonate plastic), pharmaceutical estrogens such as diethylstilbestrol (DES) and ethinyl estradiol, and phytoestrogens, which occur naturally in many plants, most notably in soybeans in the form of genistein and related substances. There are a few known ER antagonists, or antiestrogens. Antiandrogens, or androgen receptor (AR) antagonists, include the fungicide vinclozolin, the DDT metabolite p,p′-DDE, certain phthalates (a group of chemicals used to soften polyvinyl chloride plastics), and certain other PCBs. And there are other types of EDCs that affect particular endocrine targets. The various EDCs differ greatly in their potencies relative to natural hormones, and in their affinity for target receptors. Some have been shown to act via non–receptor-mediated mechanisms, for example by interfering with hormone synthesis.
In many well-documented cases of high-level fetal exposures to known EDCs such as DES, certain PCBs, and DDT, the answer to the question of whether exposure is associated with gender-related effects is clearly yes. But high-level exposures such as these are relatively rare and isolated. The debate today centers on low-dose exposures—generally defined as doses that approximate environmentally relevant levels—and the idea that low-dose intrauterine exposure to some EDCs during certain critical windows of development can have profound, permanent impacts on subsequent fetal development and adult outcomes.
Critics of this idea maintain that thus far there is no credible evidence to suggest that low-dose exposures cause any adverse human health effects. But if low-dose exposures were confirmed to be the threat that proponents of the concept insist they are, public health would clearly be at risk, regulatory agencies’ risk assessment approach would need to be revised, and certain common chemicals—including some that are massively produced and economically important—would likely disappear from the marketplace.
In a June 2000 EHP review article on human health problems associated with EDCs, Stephen Safe, director of the Center for Environmental and Genetic Medicine at Texas A&M University, concluded that “the role of endocrine disruptors in human disease has not been fully resolved; however, at present the evidence is not compelling.” Frederick vom Saal, a developmental biologist at the University of Missouri–Columbia, disagrees, particularly in light of the research that’s been presented in the years since that review. “The jury is not out on human effects,” he says. “In terms of the amount of information we have in animals and the amount of information we have in humans, clearly there is a huge difference, but that’s a lot different than saying the jury is out on whether EDCs influence humans.” One thing both scientists might agree on, though, is that right now there are still more questions than answers.
A Delicate Process
Evidence of Effects
The Phthalate Connection
EDCs and Sex Ratios
How Low Do They Go?
Connecting the Gender Dots
The Road Ahead
Continue reading: Are EDCs Blurring Issues of Gender?, Environ Health Perspect. Oct 2005; 113(10): A670–A677., PMCID: PMC1281309.
High levels of antibiotics in China’s rivers expose millions of nearby residents and local ecosystems to grave risks
China Central Television reported this week that a very excessive amount of antibiotics has been found in water tested from China’s major rivers, as well as in tap water in East China’s Jiangsu Province, exposing millions of nearby residents and local ecosystems to grave risks.
The report said that the high concentration of antibiotics was created by pharmaceutical drug producers illegal discharges and by poultry farmers abuse.
Read High levels of antibiotics in China’s rivers, Global Times, 2014-12-26.
In this 2006 study, birth weight was inversely associated with mother’s smoking status and use of DES during pregnancy
2006 Study Abstract
Exploring whether the positive association between birth weight and breast cancer risk differs by other breast cancer risk factors may help inform speculation about biological mechanism. In these data, high birth weight was associated with breast cancer risk in younger and in more educated women, but was not associated overall.
Birth weight was not associated with attained age, age at first birth/parity, menopausal status, or family history of breast cancer, but was inversely associated with mother’s smoking status and use of DES during pregnancy. An inverse association between birth weight and age at menarche was also suggested.
Birth weight and breast cancer risk, NCBI, PMID: 16641898, Br J Cancer. 2006 Jun 5;94(11):1734-7 PMC2361301. Full text link.
With new technologies we can now examine the whole of a person’s DNA — their genome — quicker and cheaper than ever before. In this video, Vivienne Parry OBE introduces the fundamentals of genomics and its growing importance for healthcare.
Early-stage sex cells research in Cambridge has potential to help people with fertility problems
Scientists at the University of Cambridge working with the Weizmann Institute have created primordial germ cells – cells that will go on to become egg and sperm – using human embryonic stem cells. Although this had already been done using rodent stem cells, the study, published today in the journal Cell, is the first time this has been achieved efficiently using human stem cells.
When an egg cell is fertilised by a sperm, it begins to divide into a cluster of cells known as a blastocyst, the early stage of the embryo. Within this ball of cells, some cells form the inner cell mass – which will develop into the foetus – and some form the outer wall, which becomes the placenta. Cells in the inner cell mass are ‘reset’ to become stem cells – cells that have the potential to develop into any type of cell within the body. A small number of these cells become primordial germ cells (PGCs) – these have the potential to become germ cells (sperm and egg), which in later life will pass on the offspring’s genetic information to its own offspring.
“The creation of primordial germ cells is one of the earliest events during early mammalian development,” says Dr Naoko Irie, first author of the paper from the Wellcome Trust/Cancer Research UK Gurdon Institute at the University of Cambridge. “It’s a stage we’ve managed to recreate using stem cells from mice and rats, but until now few researches have done this systematically using human stem cells. It has highlighted important differences between embryo development in humans and rodents that may mean findings in mice and rats may not be directly extrapolated to humans.”
Professor Surani at the Gurdon Institute, who led the research, and his colleagues found that a gene known as SOX17 is critical for directing human stem cells to become PGCs (a stage known as ‘specification’). This was a surprise as the mouse equivalent of this gene is not involved in the process, suggesting a key difference between mouse and human development. SOX17 had previously been shown to be involved in directing stem cells to become endodermal cells, which then develop into cells including those for the lung, gut and pancreas, but this is the first time it has been seen in PGC specification.
The group showed that PGCs could also be made from reprogrammed adult cells, such as skin cells, which will allow investigations on patient-specific cells to advance knowledge of the human germline, infertility and germ cell tumours. The research also has potential implications for understanding the process of ‘epigenetic’ inheritance. Scientists have known for some time that our environment – for example, our diet or smoking habits – can affect our genes through a process known as methylation whereby molecules attach themselves to our DNA, acting like dimmer switches to increase or decrease the activity of genes. These methylation patterns can be passed down to the offspring.
Professor Surani and colleagues have shown that during the PGC specification stage, a programme is initiated to erase these methylation patterns, acting as a ‘reset’ switch. However, traces of these patterns might be inherited – it is not yet clear why this might occur.
“Germ cells are ‘immortal’ in the sense that they provide an enduring link between all generations, carrying genetic information from one generation to the next,” adds Professor Surani. “The comprehensive erasure of epigenetic information ensures that most, if not all, epigenetic mutations are erased, which promotes ‘rejuvenation’ of the lineage and allows it to give rise to endless generations. These mechanisms are of wider interest towards understanding age-related diseases, which in part might be due to cumulative epigenetic mutations.”
The research was funded by the Wellcome Trust and BIRAX (the Britain Israel Research and Academic Exchange Partnership).
Sources and more information
Egg and sperm race: Scientists create precursors to human egg and sperm, University of Cambridge, 24 Dec 2014.
SOX17 Is a Critical Specifier of Human Primordial Germ Cell Fate, cell, doi.org/10.1016/j.cell.2014.12.013.
Scientists use skin cells to create artificial sperm and eggs, theguardian, 24 December 2014.