Table 2.

Summary of experimental studies on animals reporting associations between prenatal or perinatal exposure to BPA alternatives (BPS and BPF) and health outcomes.

Model System	BPs Exposure System	Main Outcomes	Reference
	Dose/Period
Pregnant sheep	Subcutaneous injections BPA or BPS (0.5 mg kg−1 BW)/daily from gestational day 30 to 100	BPA- and BPS-exposed fetal skeletal muscle showed:   ↑ muscle fiber hypertrophy   ↑ expression of myogenic regulatory factors	[30]
Mouse dams	Oral administration to dams before pregnancy BPA or BPS (200 μg kg−1 BW)/daily for 2 weeks and after breeding until embryonic day 12.5	Both BPA- and BPS-exposed placentas showed:   ↓ serotonin   ↑ dopamine	[31]
Pregnant sheep	Injection to pregnant sheep BPS or BPA (0.5 mg kg−1 BW, internal fetal doses ~2.6 ng mL−1 of BPA and ~7.7 ng mL−1 of BPS)/daily from gestational day 30 to 100	BPS-exposed placentas showed:   ↓ E-cadherin protein expression by 50%.   ↓ binucleate cells by ~20%.   ↑ glial cell missing-1 protein expression by   ~3 folds	[32]
Pregnant rats	Oral administration to dams during pregnancy BPA, BPS, and BPF (1 or 5 mg kg−1 BW)/daily from gestational days 6 to 21	BPS- and BPF-exposed dams showed:   ↑ spontaneous abortions   (over 80% of dams, BPF only)   ↓ number of corpora lutea	[33]
Pregnant mice	Oral administration to dams during pregnancy BPA or BPF (0 or 10 mg kg−1 BW)/daily from gestational day 11.5 to 18.5	Prenatal BPF-exposed offspring showed:   ↑ anxiety and depressive state	[34]
Zebrafish embryos	Exposed in a test solution BPA or BPS (0.0068 μM)/daily until day 5 postfertilization	BPA and BPS exposure showed:   ↑ neurogenesis within the hypothalamus by   180% for BPA and 240% for BPS (resulted in    later   hyperactive behaviors in the zebrafish   larvae)	[35]
Zebrafish embryos	Exposed in a test solution BPS (0, 0.03, 0.3 and 3.0 mg L)/daily until day 6 postfertilization	BPS exposure showed:   ↓ locomotor behavior   ↑ oxidative stress   ∆ neurodevelopment genes expression	[36]
Pregnant rats	Oral administration to dams Mixture of BPA, BPS, and BPF (150 µg kg−1 BW)/daily from gestational day 8 to day of birth	Prenatal bisphenols-exposed offspring showed:   ∆ expression of over 2000 genes   (amygdala was the most affected region).   ↑ genes expression in the hypothalamus	[37]
Pregnant mice	Oral administration to dams during pregnancy BPS (100 μg kg−1 BW)/daily from gestational day 7 to postnatal day 21	Perinatal BPS-exposed male offspring showed:   ↑ body weight   ↑ epididymal white adipose tissue   ↑ liver triglyceride and cholesterol   ↑ liver lipid accumulation	[38]
Pregnant rats	Oral administration to dams BPA or BPS (0.0, 0.4, 4.0 μg kg−1 BW)/daily from gestational day 4 to 21	Prenatal BPS-exposed male offspring showed:   ∆ feed efficiency   ∆ leptin signaling   ↑ adipocyte hypertrophy   ↑ fatty liver   ↑ adipose tissue inflammation   ↑ oxidative stress in adipose tissue	[39]
Adult rats	Administration through dams’ drinking water BPS (4 and 40 μg kg−1 BW)/daily for 2 months before mating	Prenatal BPS-exposed male offspring showed (lower dose):   ↑ body weight   ↓ glucose tolerance   ↓ insulin sensitivity	[40]
Pregnant mice	Oral administration to dams during pregnancy and lactation BPS (0.05 or 20 mg kg−1 BW)/daily from gestational day 6 to postnatal day 21	Perinatal BPF-exposed offspring showed:   ↓ body weight   ↑ glucose tolerance   ↑ pancreatic β-cell proliferation	[41]
Pregnant mice	Oral administration to dams BPS (50 μg kg−1 BW)/daily during gestation	Prenatal BPS-exposed male offspring showed:   ↑ body weight   ∆ lipid metabolism   ↑ liver triglyceride   ↑ adipocyte hypertrophy   ↑ hepatic lipid deposition	[42]
Zebrafish	Exposed in a test solution BPS (1, 10, 100, and 1000 mg L−1)/daily for 120 days	Prenatal BPS-exposed offspring showed:   ∆ lipid metabolism	[43]
Mice dams	Dermal exposure to dams BPA, BPS, or BPF (5 or 50 μg kg−1 BW)/daily from gestation day 15 to postnatal day 21	Perinatal BPF-exposed offspring showed:   ∆ immune responses	[44]
Pregnant mice	Exposed to drinking water from dams BPS (1.5 µg kg−1 BW)/daily from gestational day 0 until weaning of offspring	Perinatal BPS-exposed offspring showed:   ↑ inflammatory response   (observed in F1 and F2)	[45]
Lactating rats	Oral administration to dams BPF (0.0365 and 3.65 mg kg−1 BW)/daily	Perinatal BPF-exposed female and male offspring showed:   ↑ liver inflammation	[46]
Lactating rats	Oral administration to dams BPF (0.0365 and 3.65 mg kg−1 BW)/daily until postnatal day 6	Perinatal BPF-exposed female and male offspring showed:   ↑ lipid peroxidation   ↑ oxidative stress	[47]

Abbreviations. BPs: bisphenols; BPA: bisphenol A; BPS: bisphenol S; BPF: bisphenol F; BW: body weight; (↑): increase; (↓): decrease; (∆): alteration/changes.