Even at the highest doses, the parent and offspring mice appeared outwardly healthy. Maternal and pup body weights were normal at birth and the pups grew as expected.
But when the MEHP-exposed pups grew up and bred in the lab, several reproductive changes became apparent compared to the mice that weren't exposed. Those exposed to the 500 mg and 1,000 mg doses started estrus (being in heat) late, but then stayed in it for a longer time each month. Initially, Moyer noticed, the offspring mice exposed to the highest dose also delivered significantly larger litters of eight or nine pups than unexposed mice who typically bore five or six pups.
Over time, though, the most exposed mice were able to bear pups for less time. Mice exposed to the 1,000 mg dose in utero were no longer able to bear a litter a month earlier than unexposed mice.
The researchers also looked at other indicators of reproductive health, including egg follicle counts and key hormone levels. They found that highly exposed mice had more of some kinds of follicles than mice who weren't exposed. Early in the shortened reproductive lives of the highly exposed mice, the researchers found higher levels of hormones like estradiol, but after a year, the estradiol levels of those mice were significantly less than in control mice.
By then, however, those higher estradiol levels had done some permanent damage. The mammary glands of highly exposed mice exhibited a visibly striking degree of abnormal cell growth. Hixon said the growth could be considered a precursor to cancer.
Experiment yields new hypotheses
Hixon and Moyer said they can't be sure what underlies all the changes in reproductive physiology that they observed, but they did look at gene expression in the exposed mice and found that among more than 80 genes whose expression was altered, a few
|Contact: David Orenstein|