8 Journal of Toxicology Table 6: Eﬀect of SE5-OH administration on the F1 generation rat dam reproductive performance. (Dmogse/kg/day) Mean estrus cycle iIrnrceigduelnacreeostfrus cycle Number of Mesatrtuinsg pDearyioodf conceiving Copulation index (%)A Fertility index (%)B 0 4.36 ± 0.46# 0.1 ± 0.6 3.1 ± 2.8 95.5 85.7 (n = 24) 0/24 (n = 22) (n = 21) (21/22) (18/21) 200 4.31 ± 0.45 0.2 ± 0.7 2.8 ± 1.8 95.7 86.4 (n = 21) 2/23 (n = 23) (n = 22) (22/23) (19/22) 1000 4.39 ± 0.41 0.1 ± 0.2 2.3 ± 1.3 100.0 95.0 (n = 20) 0/20 (n = 20) (n = 20) (20/20) (19/20) 2000 4.30 ± 0.43 0.0 ± 0.0 2.5 ± 1.5 100.0 95.5 (n = 21) 1/22 (n = 22) (n = 22) (22/22) (21/22) #Mean ± standard deviation; Anumber of copulated females/number of pairs; Bnumber of pregnant females/number of copulated females; n: number of mating pairs. Table 7: Eﬀects of SE5-OH administration on F0 generation rat dam gestation and delivery parameters. Birth indexA (%) Gestation indexB (%) Dose (mg/kg/day) 0 200 1000 2000 n n n Gestation length (days) 22.3 ± 0.5 Number of implantation sites 15.0 ± 3.9 Number of oﬀspring born alive 13.8 ± 4.1 24 23 22 22.2 ± 0.4 22.3 ± 0.6 22.0 ± 0.3 25 24 22 15.1 ± 3.6 15.3 ± 1.7 14.7 ± 2.1 25 24 22 13.8 ± 3.4 13.6 ± 3.3 13.8 ± 2.3 87.12 ± 21.64 25 24 22 89.03 ± 20.48 89.27 ± 19.68 93.63 ± 9.28 n 22 22 22 22 Signiﬁcantly diﬀerent from control: ∗P < .05, ∗∗P < .01; Abirth index = (number of oﬀspring born alive divided by the number of implantations); Bgestation index = (number of females with live oﬀspring divided by the number of pregnant females); n: number of dams per group. 96 95.8 100.0 100.0 (delivering approx. 26.16 mg equol/kg body weight/day to the rat) for three months to ovariectomized rats signiﬁcantly increased serum prolactin and lutenizing hormone levels (P < .05), but had no eﬀect on pituitary estrogen receptor (ER)-α or -β gene expression. However, equol administration did increase an isoform of the estrogen receptor (Terp-1) in the pituitary of these ovariectomized rats, and increased the number of terminal ducts and type II lobules, compared to control rats. Equol dosed at 3.68 mg/kg/day in this same study had no eﬀect on rat mammary tissue. In this same rat model, equol (26.16 mg/kg body weight/day) signiﬁcantly increased uterine weights and increased the epithelial height and thickness of the uterine stroma and myometrium, and signiﬁcantly increased levels of uterine insulin-like growth factor 1, progesterone receptor, and complement protein 3 mRNA, while 3.68 mg equol/kg bodyweight/day had no eﬀect [44]. Subcutaneous administration of up to 1000 μg equol in rat pups during PND 1–5 or PND 10–14 lowered uterine weight at later ages, but did not aﬀect ER levels [45]. Equol administration (approx. 27.48 mg/kg body weight/day) in ovariectomized rats for six weeks increased uterine weight, decreased weight gain, and attenuated tra- becular bone loss (but not proximal tibia bone loss), while increasing its density, indicating mild bone sparing eﬀects [46]. These studies indicate that there is an uncertain degree of diﬀerence in species- and organ-speciﬁc sensitivity to equol administration. SE5-OH is a unique fermented soy germ food product that is intended to deliver equol to individuals who cannot produce it endogenously. The studies currently described were conducted to determine any potential developmental and reproductive eﬀects of SE5-OH. In the developmen- tal study, isolated embryo-fetal eﬀects were noted dur- ing necropsy, which included the fusion of placentae in one dam in the 200 mg/kg/day dose group. As no other placental abnormalities were identiﬁed in this study, this eﬀect was determined not to be test article-related. One control group fetus and one high-dose fetus were found to have a ventricular septal defect, and visceral variants that included a thymic neck remnant, supernumerary coronary ostium, left umbilical artery, and renal pelvis dilations which occurred with equal incidence in these dose groups and were determined not to be test article-related. Dumbell ossiﬁcation of the thoracic centrum was signiﬁcantly lower in the high-dose group, but the overall incidence of the observed skeletal variants (as indicated in Table 4) was determined not to be test article-related because they are similarly seen in untreated Crl:CD(SD) rats. An increase in relative (but not absolute) liver weight was noted in the F0 1000 and 2000 mg/kg/day dams, and