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Intramural Papers of the Month

By Robin Arnette
January 2009

Telomere Length Is Associated with Obesity and Weight Gain

Investigators at NIEHS report that shorter telomeres - noncoding double-stranded repeats at the ends of chromosomes - are associated with higher body mass index (BMI) and weight gain in adulthood. Since short telomeres have been linked to an increased risk of developing age-related diseases, these findings support the hypothesis that obesity may accelerate the aging process. In addition, the findings highlight the importance of maintaining a healthy weight in adulthood.

The investigators studied 647 women from the approximately 50,000 women ages 35-74 who are participating in the Sister Study, a prospective study of environmental and genetic risk factors for breast cancer. The women's height, weight and waist circumferences were measured, and telomere length was estimated by extracting DNA from blood samples and subjecting the samples to real-time quantitative polymerase chain reaction (PCR).

There was an inverse relationship between telomere length and both current and past BMI. While telomere length was associated with weight gain and weight cycling, the results suggested that duration of obesity may be more important than weight gain, per se, since among women over 40, telomeres were shortest in women who were overweight or obese both in their 30s and when they enrolled in the study.

Citation: Kim S, Parks CG, DeRoo LA, Chen H, Taylor JA, Cawthon RM, Sandler DP ( Exit NIEHS. 2009. Obesity and weight gain in adulthood and telomere length. Cancer Epidemiol Biomarkers Prev 18(3):816-820.

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Mouse Allergens Associated with Asthma Symptoms

Recent findings suggest that mouse allergen exposure in the home is an important risk factor for allergic asthma and contributes independently to asthma morbidity among allergic individuals. According to the research team, comprised of scientists from NIEHS and the Constella Group, LLC, levels of mouse urinary protein (MUP) greater than 1.6 µg/g in the home increased the odds of having asthma symptoms in the past year by two-fold. These results were generated as part of the National Survey of Lead and Allergens in Housing (NSLAH), the first study to evaluate the importance of residential mouse allergen exposures among the general U.S. population.

The NSLAH was a cross-sectional study that surveyed 2,456 individuals living in 831 housing units in 75 different locations throughout the U.S. Participants completed questionnaires that provided information on demographics, household characteristics and health status. Members of the research team vacuumed dust from various indoor sites and used a polyclonal immunoassay to determine the concentration of MUP.

Eighty-two percent of the homes surveyed had detectable levels of MUP, and 35 percent of the homes had MUP concentrations greater than 1.6 µg/g. Allergic individuals who were exposed to these elevated levels of MUP had an increased risk of experiencing asthma symptoms, while those who did not have allergies were unaffected.

Citation: Salo PM, Jaramillo R, Cohn RD, London SJ, Zeldin DC ( Exit NIEHS. 2009. Exposure to mouse allergen in U.S. homes associated with asthma symptoms. Environ Health Perspect 117(3):387-391.

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Female Mice Neonatally-Treated with Genistein Exhibit Reproductive Abnormalities

The oviductal environment and uterus of female mice neonatally treated with genistein, a phytoestrogen found in soy products, develop abnormalities that contribute to reproductive failure. Investigations conducted by NIEHS researchers determined that although the eggs from these mice were normal, reduced embryo survival in the abnormal oviductal environment and the inability of the uterus to sustain pregnancy contributed to their complete infertility.

On neonatal Days 1-5, female mouse pups received subcutaneous injections of corn oil (control) or 50 mg/kg/day of genistein. At six to nine weeks of age, eggs were harvested following induced ovulation. Eggs from both groups were easily fertilized in vitro and one cell embryos could be cultured equally to the blastocyst stage. When these blastocysts were transferred to pseudopregnant recipients, the number of live pups produced was similar to controls. However, if embryos were left to develop in the oviduct, about half failed to develop to the blastocyst stage and most of the remaining embryos failed to implant; no pups were born.

Previous studies suggested that the uterus of genistein-treated mice is less responsive to estrogens. Because implantation is hormone-dependent, the authors propose that the limited response to hormonal cues could be responsible for reproductive failure.

Citation: Jefferson WN, Padilla-Banks E, Goulding EH, Lao SP, Newbold RR, Williams CJ ( Exit NIEHS. 2009. Neonatal exposure to genistein disrupts ability of female mouse reproductive tract to support preimplantation embryo development and implantation. Biol Reprod 80(3):425-431.

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Novel Role for Estrogen Receptor Beta in Granulosa Cells

According to NIEHS researchers, estrogen receptor beta (ERβ) is required for the optimal accumulation of cAMP in follicle stimulating hormone (FSH)-stimulated mouse granulosa cells. The published findings are the first to indicate the role that ERβ plays in the induction of the cAMP pathway in mouse granulosa cells and the negative effects on ovulation and fertility.

Previous in vivo and in vitro studies demonstrated that granulosa cells from ERβ-/- preovulatory follicles exhibited a reduced response to FSH-induced differentiation as evidenced by an attenuated response to luteinizing hormone (LH). The research team furthered this research by using microarray analysis to identify genes that need ERβ for induction by comparing granulosa cells from ERβ-/- and ERβ+/+ mice following FSH exposure. In addition, the team used granulosa cell cultures to examine the purpose of ERβ in the cAMP pathway.

Results indicated a 50 percent reduction in cAMP levels in ERβ-/- compared to controls and a reduction in CREB phosphorylation in FSH-treated ERβ-/- granulosa cells.

Citation: DeRoo BJ, Rodriguez KF, Couse JF, Hamilton KJ, Collins JB, Grissom SF, Korach KS ( Exit NIEHS. 2009. Estrogen receptor beta is required for optimal cAMP production in mouse granulosa cells. Mol Endocrinol Mar 26 [Epub ahead of print].

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