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Table 1 Summary of results on mammary gland development and mammary tumorigenesis obtained in mice and rats exposed to diethylstilbestrol in utero, at birth, during neonatal period (between days 0 and 5) or postnatally

From: Maternal exposure to diethylstilbestrol during pregnancy and increased breast cancer risk in daughters

Reference Model DES dose
(total)
Time of administration Effect on reproductive systema Effect on mammary gland or mammary cancer
Effects on mammary gland      
Nagasawa et al. 1978 [12] Balb/cfC3H mice 5 μg 0-5 Postnatal 100% no CL Hyperplasia↑
20 μg 0-5 Postnatal 100% no CL
Boylan 1978 [13] Rat 1.2 μg Week 2 G Percentage live deliveries: 97/F1 94% Normal
12 μg Week 2 G 50% Normal
60 μg Week 2 G 27% Normal
120 μg Week 2 G 33% Normal
1,200 μg Week 2 G No surviving pups  
12,000 μg Week 2 G No surviving pups Normal
1.2 μg Week 3 G 81/F1 78% Slightly enlarged nipples
120 μg Week 3 G 62/F1 57%  
12,000 μg Week 3 G No surviving pups  
Bern et al. 1987 [14] Balb/c mice 5 × 10-5 μg 0-5 Postnatal Cervicovaginal lesions12%, 65% no CL HANs 10%
5 × 10-4 μg 0-5 Postnatal 19%, 88% no CL HANs 19%
5 × 10-3 μg 0-5 Postnatal 42%, 95% no CL HANs 41%
5 × 10-2 μg 0-5 Postnatal 63%, 100% no CL HANs 7%
5 × 1 μg 0-5 Postnatal 80%, 100% no CL HANs 12%
Vassilacopoulou and Boylan 1993 [15] ACI rat 4 + 4 μg 15 + 18 G Not studied Hypodifferentiation and hyperproliferation
Effect on mammary tumorigenesis      
Boylan and Calhoon 1979 [16] Rat/DMBA 1.2 μg Week 2 G Not studied Multiplicity↑
1.2 μg Week 3 G Multiplicity↑
Boylan and Calhoon 1983 [18] Rat/DMBA 0.6 + 0.6 μg 15 + 18 G Not studied Incidence + multiplicity↑
Rothschild et al. 1987 [19] ACI rat 0.4 + 0.4 μg 15 + 18 G Not studied No change
4 + 4 μg 15 + 18 G Incidence↑
Ninomiya et al. 2007 [20] Rat/DMBA 0.1 μg Birth (one dose) Normal cycle, 40% CL Multiplicity↑
1 μg Birth (one dose) 19% PE, 50% CL, U w↓ Incidence + multiplicity↑
10 μg Birth (one dose) 77% PE, 92% CL, U w↓ Multiplicity↑
100 μg Birth (one dose) 100% PE, 100% CL, O + U w↓ No change
Yoshikawa et al. 2008 [22] Rat/DMBA 14 x 1 μg 0-14 Postnatal 100% PE, no CL, O + U w↓, E2 and P↓ Incidence↓
5 x 1 μg 0-5 PE, no CL, O + U w↓, E2 and P↓ Incidence↓
9 x 1 μg 6-14 PE, no CL, O + U w↓ No change
Kawaguchi et al. 2009 [21] Rat/DMBA 0.1 ppm 0-21 G Few surviving pups  
1 ppm 0-21 G No surviving pups  
10 ppm 0-21 G No surviving pups (Assessed 10 weeks after
100 ppm 0-21 G No surviving pups DMBA exposure):
0.1 ppm 13-21 G 11% no CL Incidence + multiplicity↑
1 ppm 13-21 G 30% no CL Incidence + multiplicity↑
10 ppm 13-21 G Very few surviving pups Incidence↑
100 ppm 13-21 G No surviving pups  
  1. aIn control mice, corpora lutea (CL) is present in about 31 to 36% of adults, whilst in control rats it is present in 100% of adult animals. DES, diethylstilbestrol; DMBA, dimethylbenz[a]antracene; E2, estradiol; F1, F1 generation; G, gestation; HAN, hyperplastic alveolar nodule; O, ovary; P, progesterone; PE, persistent estrus; U, uterus; w, weight.