A look at the latest research

EXPOSURES TO EDCs
MAY LESSEN QUALITY OF LIFE IN FUTURE GENERATIONS

Studies on rats have shown that endocrine-disrupting chemicals (EDCs) impact not only future generations, but also how these descendants respond to stress during adolescence. A new study, published in the journal Endocrinology, has revealed that the sexes differ profoundly in these effects. That is, females with a history of exposure respond very differently to stress and exhibit phenotypes that are much more compromised than males.

Researchers led by David Crews, PhD, of the University of Texas at Austin, wrote that the legacy of exposures to EDCs “has permanently altered the present and future health of humans and wildlife.” The paper makes the distinction between “context-dependent” epigenetic modifi cations, which are not heritable because the germ cells are not affected, and “germline-dependent” epigenetic modifications, which “manifest each generation even in the absence of the causative agent.” They wrote: “This is the case for several EDCs, notably, vinclozolin, bisphenol A, and tributyltin. Such transgenerational modifications affect all levels of biological organization, from gene regulation to behavioral interactions of conspecifics.”

“I have shown previously the transgenerational effects of EDCs on behavior of the descendant generations (F3), (Crews et al. PNAS, 2007),” Crews, says. “More recently, this was extended to a novel two-hit, three-generations apart model to demonstrate how restraint stress experienced during adolescence of the F3 descendants changes their physiology, neural metabolism, and gene expression in adulthood.”

Crews and his team focused on vinclozolin, a commonly used fungicide with demonstrated antiandrogenic properties. They used the two-hit, three-generations apart model, testing how F3 descendants of rats given in utero exposures to vinclozolin reacted to stress in their own lives, focusing on sexually dimorphic phenotypic outcomes. The scientists subjected the adult rats, male and female F3 vinclozolin- or vehicle-lineage, stressed or non-stressed, to a battery of tests, behaviorally characterizing them, measuring hormone levels, and analyzing brain function and anatomy.

“Results showed that the effects of ancestral exposure to vinclozolin converged with stress experienced during adolescence in a sexually dimorphic manner,” the authors wrote. “Debilitating effects were seen at all levels of the phenotype, including physiology, behavior, brain metabolism, gene expression, and genome-wide transcriptome modifi cations in specific brain nuclei.” There were dramatic differences in the reactions between males and females, with females significantly more vulnerable to the transgenerational effects of vinclozolin on anxiety but not sociality tests.

The researchers concluded by stating that the consequences of “global contamination and stressful experiences encountered by living descendants is likely to have its own specific risk for males and females for a given spectrum of adverse outcomes. Importantly, the gene expression patterns generally support the functional behavioral and brain transcriptome differences that were observed. The implications of these results for the protection of human health and endocrine-based questions target questions of morbidity and the quality of life.”

“The most signifi cant aspect of this paper is the striking difference between females and males at all levels, from physiology, behavior, brain chemistry, and gene expression in neural networks,” Crews says. “Females are much more sensitive when these two elements (ancestral exposure and stress during adolescence of the descendants) are combined. This, in turn, provides a new way of viewing the effects of nature (ancestral exposure) and nurture (stress during adolescence) in shaping the adult phenotype and the importance of sex differences. The latter is very much in line with the recent mandate by NIH to consider both sexes in future studies in biomedical research. Finally, it illustrates the value of considering how modern day animals whose ancestors have been exposed to EDCs perceive and respond differently to common challenges in their life history.”

Couples with High Cholesterol Take Longer to Conceive

Couples may take longer to conceive a child when one, or both partners, has high cholesterol, according to a new study published in the Journal of Clinical Endocrinology & Metabolism.

Schisterman, MS, PhD, of the National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Md., examined the rate of pregnancies among 501 heterosexual couples trying to conceive in Michigan and Texas from 2005 to 2009. Of the couples who were part of the Longitudinal Investigation of Fertility and the Environment (LIFE) study, 347 became pregnant over the course of 12 months, 54 couples did not conceive a child, and 100 couples withdrew from the study, including some whose plans to have a child changed.

The scientists measured the total and free amounts of cholesterol in the blood of the couples and found that couples in which one or both partners had high levels of cholesterol took longer to become pregnant.

The authors concluded that serum-free cholesterol concentrations in both men and women are associated with time to pregnancy, highlighting the importance of cholesterol and lipid homeostasis for male and female fecundity. “In addition to raising the risk of cardiovascular disease, our findings suggest cholesterol may contribute to infertility,” Schisterman says. “Our results suggest prospective parents may want to have their cholesterol checked to ensure their levels are in an acceptable range.”

People with T2D hieve Superior Outcomes
With Insulin Pumps . Insulin Injections

Patients with type 2 diabetes achieve better glucose control with insulin pumps than their counterparts who administer multiple daily injections, according to a study recently published in The Lancet.

Researchers led by Yves Reznik, MD, of the Endocrinology and Diabetes Department, CHU Côte de Nacre, in Caen Cedex, France, wrote, “Many patients with advanced type 2 diabetes do not meet their glycated haemoglobin targets, and randomised controlled studies comparing the efficacy of pump treatment and multiple daily injections for lowering glucose in insulin-treated patients have yielded inconclusive results. We aimed to resolve this uncertainty with a randomised controlled trial (OpT2mise).”

The global, randomized, controlled study analyzed 331 patients, ranging in age from 30 to 75 years, from Canada, Europe, Israel, South Africa, and the U.S. The results showed that those using insulin pumps achieved a mean A1C (average blood glucose) reduction of 1.1% compared to only a 0.4% reduction by those using multiple daily injections. This improvement in glucose control was achieved without any episodes of severe hypoglycemia. In addition, those in the insulin pump group lowered the total daily dose of insulin by more than 20%. There was no difference in weight gain between the two groups.

The authors concluded, “In patients with poorly controlled type 2 diabetes despite using multiple daily injections of insulin, pump treatment can be considered as a safe and valuable treatment option.”

PCOS Linked to Low-Grade
Inflammation during Pregnancy

Women who have polycystic ovary syndrome (PCOS) are more likely to experience chronic low-grade inflammation during pregnancy than their healthy counterparts, according to research recently published in the Journal of Clinical Endocrinology & Metabolism (JCEM).

Investigators led by Stefano Palomba, MD, of the Arcispedale of Santa Maria Nuova of Reggio Emilia in Reggio Emilia, Italy, evaluated 150 pregnant women who had PCOS and 150 pregnant women of about the same age and body mass index, tracking biological markers of inflammation. They found that expectant mothers with PCOS had significantly higher markers of inflammation, including white blood cell counts and C-reactive protein.

“Women who have PCOS often exhibit low-level inflammation,” Palomba says. “Our research found this state of inflammation worsens during pregnancy. Other studies have identified a connection between inflammation biomarkers and pregnancy complications such as preeclampsia and gestational diabetes. The abnormal inflammation seen in women with PCOS may be a factor in the development of these conditions.”

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