North Carolina State University
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Oct. 20, 1999
Media Contacts:
Dr. John Vandenbergh, 919/515-5174 or [email protected]
Andrew Hotchkiss, 919/515-3883 or [email protected]
Tim Lucas, News Services, 919/515-3470 or [email protected]
Fetal Exposure to 'Bisphenol A' Linked to Altered Growth, Early Puberty
FOR IMMEDIATE RELEASE
A study by researchers at North Carolina State University and the University of Missouri at Columbia (UM-C) has found that prenatal exposure to Bisphenol A, a chemical found in baby bottle liners, tin can linings and other products made from soft plastics, can speed postnatal growth and the onset of puberty in female mice.
The study will be published Thursday, Oct. 21, in the British science journal Nature. Its findings are relevant to human health, says co-author Andrew Hotchkiss, a doctoral student in zoology at NC State, because the amount of Bisphenol A fed to the pregnant mice was within the range humans also could be exposed to through everyday contact with soft plastic products.
"Bisphenol A leaches out of soft plastics at a very slow rate, but the rate increases with repeated use or can be induced by heat," Hotchkiss says. Scientists have long known that Bisphenol A is an estrogenic endocrine-disrupting chemical -- EEDC for short -- which can interfere with mammalian development by mimicking the action of the sex hormone estradiol. But the joint NC State-UM-C study is the first to document that exposure to such low, everyday doses of the chemical, delivered via their mother's food intake, can so dramatically affect the growth and development of female fetuses later in life.
"Very small increases in the level of endrogenous estradiol may substantially increase the sensitivity of fetuses to EECDs consumed by pregnant women, so some fetuses may be at particularly high risk for a wide array of abnormalities and diseases," the researchers write in Nature. "Our findings emphasize the need for studies to examine the relationship between maternal exposure to endocrine disrupters and subsequent health effects in the offspring."
Neither Hotchkiss nor co-author Dr. John Vandenbergh, professor of zoology at NC State, believes products made from soft plastics are intrinsically bad. "Plastics are fine materials for many uses," Vandenbergh says. "Our research simply suggests we need to know more before we decide if they're fine for all uses."
Hotchkiss and Vandenbergh's co-authors on the study were doctoral student Kembra Howdeshell of UM-C, and Drs. Kristina Thayer and Frederick vom Saal, also of UM-C. Their research was funded by the W.M. Keck Program for Behavioral Biology at NC State and through a National Institute of Environmental Health Sciences grant to UM-C.
A second key finding they report in Nature is that a fetus' position in the uterus -- whether it's located between other females, males, or one of each -- plays a key role in determining the extent to which its growth and development are ultimately affected by Bisphenol A.
In the study, 22 pregnant mice were fed Bisphenol A dissolved in oil at a dose equivalent to that found in the environment -- 2.4 ug/kg -- on days 11 through 17 of gestation. Twenty-two pregnant mice in the control group received daily doses of oil without Bisphenol A. The litters were delivered by cesarean section on day 19, allowing researchers to determine each pups' position in the uterus.
At weaning on postnatal day 22, females exposed to Bisphenol A were significantly heavier than females from the control group, although they did not differ in body weight at birth. Similarly, females exposed to Bisphenol A progressed from vaginal opening to their first vaginal estrus, a physiological change associated with a female's first postpubertal ovulation, in significantly fewer days than did control-group females.
Differences also were documented within the experimental group -- differences Vandenbergh believes are linked to the fetuses' positions in the uterus.
"In past studies, we've shown that intrauterine position determines fetal hormone levels because the hormones are transported from one fetus to the next," he says. For instance, fetuses located between two females (called 0Ms, for short) are exposed to the highest levels of estrogen, while fetuses located between one male and one female (1Ms) and two males (2Ms) are exposed to intermediate and the lowest levels, respectively.
In the new study, the researchers found that relative to fetuses in the same intrauterine positions in the control group, there was a 22 percent increase in body weight in 0M females and a 9 percent increase in weight for 1M females, but none for 2M females. Likewise, there was a significantly advanced onset of puberty in the 0Ms, a moderately advanced onset in 1Ms, and no advanced onset in 2Ms. "This suggests that endocrine imprinting during prenatal development can affect development in later years," Vandenbergh says. "Along with genetics, intrauterine position may help explain natural variability -- why one female responds differently than another to exposure to the same EEDCs."
In the bigger picture, the study's results echo human health trends over the past 50 years, he adds. "The onset of puberty in humans is coming at a younger and younger age. Over the last half-century, it's dropped about two years," says Vandenbergh. "It's a possibility that the earlier onset of puberty in humans in industrial nations correlates with exposure to environmental estrogens."
-- lucas --
NOTE TO EDITORS : An abstract of Vandenbergh and Hotchkiss' Nature article follows. For a full copy, contact Tim Lucas, NC State News Services, at (919) 515-3470 or [email protected].
"Plastic Bisphenol A speeds growth and puberty" published Oct. 21, 1999 in Nature by Kembra L. Howdeshell, Kristina A. Thayer and Frederick S. vom Saal, University of Missouri at Columbia, and Andrew K. Hotchkiss and John G. Vandenbergh, NC State University
ABSTRACT: Plastics and pesticides are examples of products that can contain estrogenic endocrine-disrupting chemicals (EEDCs) which can interfere with mammalian development by mimicking the action of the sex hormone estradiol. One such reported EEDC, Bisphenol A, is used in some plastics and leaches out of such products. We show that feeding pregnant female mice Bisphenol A at a dose that is within the range typical of environmental exposure of humans alters postnatal growth and brings on early puberty in their female offspring. Pregnant CF-1 mice were fed oil (vehicle) or Bisphenol A dissolved in oil (2.4ug/kg) on days 11-17 of gestation. Pups were delivered by cesarean section on day 19 to determine uterine position and then reared by untreated foster mothers. Intrauterine position determines fetal hormone levels because endogenous sex steroids are transported from one fetus to another. Fetuses located between 2 females (0M) are exposed to the highest levels of estrogen whereas femal
Prenatal exposure to an environmentally relevant dose of Bisphenol A alters postnatal growth and puberty in female mice. Importantly, individual differences in prenatal exposure to endogenous estradiol explains some of the natural variation in responsiveness of females to an EEDC.
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