Perinatal exposure to environmentally relevant levels of bisphenol A decreases fertility and fecundity in CD-1 mice.
BACKGROUND
Perinatal exposure to low-doses of bisphenol A (BPA) results in alterations in the ovary, uterus, and mammary glands and in a sexually dimorphic region of the brain known to be important for estrous cyclicity.


OBJECTIVE
We aimed to determine whether perinatal exposure to environmentally relevant doses of BPA alters reproductive capacity.


METHODS
Female CD-1 mice that were exposed to BPA at 0, 25 ng, 250 ng, or 25 µg/kg body weight (BW)/day or diethylstilbestrol (DES) at 10 ng/kg BW/day (positive control) from gestational day 8 through day 16 of lactation were continuously housed with proven breeder males for 32 weeks starting at 2 months of age. At each delivery, pups born to these mating pairs were removed. The cumulative number of pups, number of deliveries, and litter size were recorded. The purity of the BPA used in this and our previous studies was assessed using HPLC, mass spectrometry, and nuclear magnetic resonance.


RESULTS
The forced breeding experiment revealed a decrease in the cumulative number of pups, observed as a nonmonotonic dose-response effect, and a decline in fertility and fecundity over time in female mice exposed perinatally to BPA. The BPA was 97% pure, with no evidence of contamination by other phenolic compounds.


CONCLUSIONS
Perinatal exposure to BPA leads to a dose-dependent decline in the reproductive capacity of female mice. The effects on the cumulative number of pups are comparable to those previously reported in mice developmentally exposed to DES, a compound well known to impair reproduction in women. This association suggests the possibility that early BPA exposure may also affect reproductive capacity in women.
Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Nicolas J
NJ
Cabaton
Perinaaz R
PR
Wadia
Beverly S
BS
Rubin
Daniel
D
Zalko
Cheryl M
CM
Schaeberle
Michael H
MH
Askenase
Jennifer L
JL
Gadbois
Andrew P
AP
Tharp
Gregory S
GS
Whitt
Carlos
C
Sonnenschein
Ana M
AM
Soto
D000818:Animals; D000831:Animals, Newborn; D001559:Benzhydryl Compounds; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005298:Fertility / Q000187:drug effects*; D051379:Mice; D010636:Phenols / Q000633:toxicity*; D012098:Reproduction / Q000187:drug effects*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds