Fetal radiofrequency radiation exposure from 800-1900 mhz-rated cellular telephones affects neurodevelopment and behavior in mice.

Neurobehavioral disorders are increasingly prevalent in children, however their etiology is not well understood. An association between prenatal cellular telephone use and hyperactivity in children has been postulated, yet the direct effects of radiofrequency radiation exposure on neurodevelopment remain unknown. Here we used a mouse model to demonstrate that in-utero radiofrequency exposure from cellular telephones does affect adult behavior. Mice exposed in-utero were hyperactive and had impaired memory as determined using the object recognition, light/dark box and step-down assays. Whole cell patch clamp recordings of miniature excitatory postsynaptic currents (mEPSCs) revealed that these behavioral changes were due to altered neuronal developmental programming. Exposed mice had dose-responsive impaired glutamatergic synaptic transmission onto layer V pyramidal neurons of the prefrontal cortex. We present the first experimental evidence of neuropathology due to in-utero cellular telephone radiation. Further experiments are needed in humans or non-human primates to determine the risk of exposure during pregnancy.

Bisphenol-A exposure alters endometrial progesterone receptor expression in the nonhuman primate.

OBJECTIVE: To evaluate the effect of bisphenol-A (BPA), a xenoestrogen endocrine disruptor, on endometrial P receptor (PR) expression in nonhuman primates and human cells. DESIGN: Controlled trial in primates. SETTING: University. ANIMAL(S): African green monkeys. INTERVENTION(S): After oophorectomy, BPA (50 µg/kg/d), E(2), both, or vehicle control were administered. Estradiol and BPA were used in Ishikawa cells. MAIN OUTCOME MEASURE(S): Progesterone receptor expression using immunohistochemistry and quantitative polymerase chain reaction. RESULT(S): Progesterone receptor expression was increased in E(2)-treated primates compared with controls. Exposure to the combination of E(2) and BPA resulted in decreased PR expression compared with E(2) exposure alone. In Ishikawa cells treated with E(2), PR expression increased 5.1-fold; however, when Ishikawa cells were simultaneously treated with E(2) and BPA, PR expression was decreased to 0.6-fold that of cells treated with E(2) alone. CONCLUSION(S): Bisphenol-A alone functions as a weak estrogen. However, when administered with E(2), BPA diminishes E(2)-induced PR expression. The estrogen-like effect of BPA reported in exposed humans may be mediated by PR blockade and a resultant decrease in the estrogen inhibition normally imparted by P. Diminished PR expression may underlie previous reports linking BPA exposure to endometrial dysfunction in humans.

In utero exposure to diethylstilbestrol (DES) or bisphenol-A (BPA) increases EZH2 expression in the mammary gland: an epigenetic mechanism linking endocrine disruptors to breast cancer.

Diethylstilbestrol (DES) and bisphenol-A (BPA) are estrogen-like endocrine-disrupting chemicals that induce persistent epigenetic changes in the developing uterus. However, DES exposure in utero is also associated with an increased risk of breast cancer in adult women. Similarly, fetal exposure to BPA induces neoplastic changes in mammary tissue of mice. We hypothesized that epigenetic alterations would precede the increased risk of breast neoplasia after in utero exposure to endocrine disruptors. Enhancer of Zeste Homolog 2 (EZH2) is a histone methyltransferase that has been linked to breast cancer risk and epigenetic regulation of tumorigenesis. We examined the effect of BPA and DES on EZH2 expression and function in MCF-7 cells and in mammary glands of mice exposed in utero. DES and BPA treatment approximated human exposure. EZH2 functional activity was assessed by measuring histone H3 trimethylation. Treatment of MCF-7 cells with DES or BPA led to a 3- and 2-fold increase in EZH2 mRNA expression, respectively (p < 0.05) as well as increased EZH2 protein expression. Mice exposed to DES in utero showed a >2-fold increase in EZH2 expression in adult mammary tissue compared with controls (p < 0.05). EZH2 protein was elevated in mammary tissue of mice exposed to DES or BPA. Histone H3 trimethylation was increased in MCF-7 cells treated with BPA or DES. Similarly, mice exposed to BPA or DES in utero showed increased mammary histone H3 trimethylation. Developmental programming of EZH2 is a novel mechanism by which in utero exposure to endocrine disruptors leads to epigenetic regulation of the mammary gland.

Defining the proliferative phase endometrial defect.

OBJECTIVE: To evaluate proliferative phase endometrial development in a heterogeneous infertility population. DESIGN: Retrospective study. SETTING: University-based infertility practice. PATIENT(S): Two hundred forty-six treatment cycles. INTERVENTION(S): Clomiphene citrate or FSH ovarian stimulation, followed by IUI or IVF. MAIN OUTCOME MEASURE(S): Endometrial thickness according to transvaginal ultrasonography; clinical pregnancy rate. RESULT(S): Endometrial growth began from a nadir of approximately 4.5 mm on cycle day 4 and increased linearly to a plateau of approximately 10 mm on cycle day 9. This same pattern was observed in all cycles, regardless of pregnancy, drug, or underlying diagnosis. Follicle-stimulating hormone-stimulated cycles showed a significantly increased endometrial thickness compared with clomiphene citrate cycles (10.1 vs. 8.3 mm). Maximum endometrial thickness achieved showed a correlation with age, body mass index, and maximum E(2) level. Subjects who carried a primary diagnosis of polycystic ovary syndrome, endometriosis, or recurrent pregnancy loss all achieved a significantly lower peak endometrial thickness than control subjects. There was a trend toward increased endometrial thickness in cycles resulting in pregnancy compared with those not (10.1 vs. 9.6 mm, respectively). CONCLUSION(S): Endometrial development follows a predictable pattern, with a plateau in growth at cycle day 9. Diseases associated with infertility manifest a proliferative phase defect that can be recognized clinically.