Fetal Programming of Adult Glucose Homeostasis in Mice

BACKGROUND: Emerging evidence suggests that dietary soy and phytoestrogens can have beneficial effects on lipid and glucose metabolism. We have previously shown that male mice fed from conception to adulthood with a high soy-containing diet had reduced body weight, adiposity and a decrease in glucose intolerance, an early marker of insulin resistance and diabetes. OBJECTIVES: The purpose of this study was to identify the precise periods of exposure during which phytoestrogens and dietary soy improve lipid and glucose metabolism. Since intrauterine position (IUP) has been shown to alter sensitivity to endocrine disruptors, we also investigated whether the combination of IUP and fetal exposure to dietary phytoestrogens could potentially affect adult metabolic parameters. METHODS: Male outbred mice (CD-1) were allowed ad libitum access to either a high soy-containing diet or a soy-free diet either during gestation, lactation or after weaning. Adiposity and bone mass density was assessed by dual x-ray absorptiometry. Glucose tolerance was assessed by a glucose tolerance test. Blood pressure was examined by the tail-cuff system. RESULTS: Here we show that metabolic improvements are dependent on precise windows of exposure during life. The beneficial effects of dietary soy and phytoestrogens on adiposity were apparent only in animals fed post-natally, while the improvements in glucose tolerance are restricted to animals with fetal exposure to soy. Interestingly, we observed that IUP influenced adult glucose tolerance, but not adiposity. Similar IUP trends were observed for other estrogen-related metabolic parameters such as blood pressure and bone mass density. CONCLUSION: Our results suggest that IUP and fetal exposure to estrogenic environmental disrupting compounds, such as dietary phytoestrogens, could alter metabolic and cardiovascular parameters in adult individuals independently of adipose gain

Low Phytoestrogen Levels in Feed Increase Fetal Serum Estradiol Resulting in the “Fetal Estrogenization Syndrome” and Obesity in CD-1 Mice

doi:10.1289/ehp.10448Although estrogenic chemicals can disrupt development of the reproductive system, there is debate about whether phytoestrogens in soy are beneficial, benign, or harmful. We compared reproductive and metabolic characteristics in male and female mice reared and maintained on non-soy low-phytoestrogen feed or soy-based high-phytoestrogen feed. Removing phytoestrogens from mouse feed produces an obese phenotype consistent with metabolic syndrome, and the associated reproductive system abnormalities are consistent with FES due to elevated endogenous fetal estradiol. Laboratory rodents may have become adapted to high-phytoestrogen intake over many generations of being fed soy-based commercial feed; removing all phytoestrogens from feed leads to alterations that could disrupt many types of biomedical research

Developmental effects of endocrine-disrupting chemicals in wildlife and humans.

Large numbers and large quantities of endocrine-disrupting chemicals have been released into the environment since World War II. Many of these chemicals can disturb development of the endocrine system and of the organs that respond to endocrine signals in organisms indirectly exposed during prenatal and/or early postnatal life; effects of exposure during development are permanent and irreversible. The risk to the developing organism can also stem from direct exposure of the offspring after birth or hatching. In addition, transgenerational exposure can result from the exposure of the mother to a chemical at any time throughout her life before producing offspring due to persistence of endocrine-disrupting chemicals in body fat, which is mobilized during egg laying or pregnancy and lactation. Mechanisms underlying the disruption of the development of vital systems, such as the endocrine, reproductive, and immune systems, are discussed with reference to wildlife, laboratory animals, and humans

Chemically Bonded Phases for the Analysis of Trace Amounts of Organic Pollutants

This work describes some results of identification and determination of bisphenol A (BPA) in powdered milk by applying the gas chromatography. To determine BPA contents in the milk and to reduce the matrix interference associated with the constituents of the powdered milk, we performed the following activities. First, we ultra-centrifuged the dissolved milk solutions. Next, we preconcentrated the analyte in the supernatant using a C18 and new sorbent with chemically bonded ketoimine group solid phase extraction column. Finally, we used gas chromatography for the determination of BPA in the samples under study. A recovery of bisphenol A from spiked milk samples was also performed, with recovery result located at 91% ± 3%/94% ± 2%

Terminal Investment: Individual Reproduction of Ant Queens Increases with Age

The pattern of age-specific fecundity is a key component of the life history of organisms and shapes their ecology and evolution. In numerous animals, including humans, reproductive performance decreases with age. Here, we demonstrate that some social insect queens exhibit the opposite pattern. Egg laying rates of Cardiocondyla obscurior ant queens increased with age until death, even when the number of workers caring for them was kept constant. Cardiocondyla, and probably also other ants, therefore resemble the few select organisms with similar age-specific reproductive investment, such as corals, sturgeons, or box turtles (e.g., [1]), but they differ in being more short-lived and lacking individual, though not social, indeterminate growth. Furthermore, in contrast to most other organisms, in which average life span declines with increasing reproductive effort, queens with high egg laying rates survived as long as less fecund queens

Toward Identifying the Next Generation of Superfund and Hazardous Waste Site Contaminants

Reproduced with permission from Environmental Health Perspectives."This commentary evolved from a workshop sponsored by the National Institute of Environmental Health Sciences titled "Superfund Contaminants: The Next Generation" held in Tucson, Arizona, in August 2009. All the authors were workshop participants." doi:10.1289/ehp.1002497Our aim was to initiate a dynamic, adaptable process for identifying contaminants of emerging concern (CECs) that are likely to be found in future hazardous waste sites, and to identify the gaps in primary research that cause uncertainty in determining future hazardous waste site contaminants. Superfund-relevant CECs can be characterized by specific attributes: they are persistent, bioaccumulative, toxic, occur in large quantities, and have localized accumulation with a likelihood of exposure. Although still under development and incompletely applied, methods to quantify these attributes can assist in winnowing down the list of candidates from the universe of potential CECs. Unfortunately, significant research gaps exist in detection and quantification, environmental fate and transport, health and risk assessment, and site exploration and remediation for CECs. Addressing these gaps is prerequisite to a preventive approach to generating and managing hazardous waste sites.Support for the workshop, from which this article evolved, was provided by the National Institute of Environmental Health Sciences Superfund Research Program (P42-ES04940)

Toward Identifying the Next Generation of Superfund and Hazardous Waste Site Contaminants

Reproduced with permission from Environmental Health Perspectives."This commentary evolved from a workshop sponsored by the National Institute of Environmental Health Sciences titled "Superfund Contaminants: The Next Generation" held in Tucson, Arizona, in August 2009. All the authors were workshop participants." doi:10.1289/ehp.1002497Our aim was to initiate a dynamic, adaptable process for identifying contaminants of emerging concern (CECs) that are likely to be found in future hazardous waste sites, and to identify the gaps in primary research that cause uncertainty in determining future hazardous waste site contaminants. Superfund-relevant CECs can be characterized by specific attributes: they are persistent, bioaccumulative, toxic, occur in large quantities, and have localized accumulation with a likelihood of exposure. Although still under development and incompletely applied, methods to quantify these attributes can assist in winnowing down the list of candidates from the universe of potential CECs. Unfortunately, significant research gaps exist in detection and quantification, environmental fate and transport, health and risk assessment, and site exploration and remediation for CECs. Addressing these gaps is prerequisite to a preventive approach to generating and managing hazardous waste sites.Support for the workshop, from which this article evolved, was provided by the National Institute of Environmental Health Sciences Superfund Research Program (P42-ES04940)

The male fetal biomarker INSL3 reveals substantial hormone exchange between fetuses in early pig gestation

The peptide hormone INSL3 is uniquely produced by the fetal testis to promote the transabdominal phase of testicular descent. Because it is fetal sex specific, and is present in only very low amounts in the maternal circulation, INSL3 acts as an ideal biomarker with which to monitor the movement of fetal hormones within the pregnant uterus of a polytocous species, the pig. INSL3 production by the fetal testis begins at around GD30. At GD45 of the ca.114 day gestation, a time at which testicular descent is promoted, INSL3 evidently moves from male to female allantoic compartments, presumably impacting also on the female fetal circulation. At later time-points (GD63, GD92) there is less inter-fetal transfer, although there still appears to be significant INSL3, presumably of male origin, in the plasma of female fetuses. This study thus provides evidence for substantial transfer of a peptide hormone between fetuses, and probably also across the placenta, emphasizing the vulnerability of the fetus to extrinsic hormonal influences within the uterus