Table 2.
Metabolic parameters observed in animal studies following prenatal exposure to bisphenol A.
| Reference | Dose | Low/High Dose | Route of Exposure | Exposure Window | Strain, Species | Sex | Outcomes |
|---|---|---|---|---|---|---|---|
| [51] | 2.5 µg/kg/day | Very low | Drinking water | 30 days before mating and continued until GD 20 | SD rats | M (male) and F (female) | No effect on parameters of lipid metabolism on pregnant rats. No effect on foetus hepatic TG or TC content. |
| [43] | 1, 10, 100, and 1000 µg/kg/day | Very low, low, and high | Gavage | GD 7.5–GD 16.5 | C57BL/6J mice | M and F | In male offspring (14 weeks of age), the hepatic TG content increased significantly at 1 and 1000 µg/kg/day (very low and high doses, respectively) and liver weight increased at very low BPA dose (1 µg/kg/day). In female offspring, the hepatic TG content increased significantly at 1000 µg/kg/day (high dose). |
| [43] | 1 µg/kg/day | Very low | Gavage | GD 7.5–GD 16.5 | C57BL/6J mice | M and F | In ♂ (14 weeks) offspring, gestational exposure to low-dose BPA caused increased hepatic TG and glycogen levels and significantly elevated fasting blood glucose and insulin levels, as well as the blood glucose levels, in IPGTT and IPITT analysis. Low-dose gestational exposure to BPA did not impair glucose or lipid metabolism in adult female offspring. |
| [44] | 5 μg/kg/day | Low | Pipette | GD 19–GD 21 | C57BL/6J mice | M and F | Low gestational BPA exposure (♀) significantly increased BW (at 13, 14, 20, and 22 weeks), significantly decreased hepatic TG content, and had no effect on plasma lipid parameters, plasma insulin level, or glucose tolerance at 10 and 21 weeks. Low gestational BPA exposure (♂) significantly decreased BW (at 4 weeks), showed faster glucose clearance at 10 and 21 weeks, and significantly decreased plasma TG, FFA, UC, and VLDL, but not TC, HDL, or LDL; there was a significant increase in hepatic TC content. |
| [52] | 100 μg/kg/day | High | Gavage | GD 6–PND 21 | SD rats | M and F | High BPA did not significantly alter maternal weight gain or birth weight. ♂ BPA only increased body weight at PND 97 and energy intake (but not significant) and had no effect on body composition (fat/lean mass ratio) at birth or weaning. However, during the post-weaning to adulthood period, BPA significantly increased the fat/lean mass ratio (PND 60–90). ♂ High BPA significantly increased the amount of both hepatic TG and FFAs (PND 1). |
| [55] | 2.5, 25, or 250 µg/Kg/day | Very low, low, and high | Diet | Month virgin state plus 20 days during pregnancy | SD rats | M and F | During pregnancy, the mother’s weight in the third week of pregnancy was significantly lower in the 2.5 µg/Kg/day BPA group. Foetal weight at birth was significantly increased in rats treated with 2.5 µg/kg/day BPA. |
| [45] | 0.5 or 50 µg/Kg/day | Very low and low | Drinking water | GD 3.5–PND 22 | Fischer 344 rats | M and F | (♀, ♂) A very low BPA dose (0.5 µg BPA/kg) was correlated with insulin hypersecretion, while 50 µg BPA/kg was associated with reduced insulin secretion from both rat offspring and dams (5 and 52 weeks, respectively). |
| [56] | 0.05, 0.5, or 5 mg/Kg/day | Very low, low, and high | Subcutaneous | GD 30–90 | Sheep | F | (♀ at ∼21 months) No effect on plasma TG content for all BPA doses. Significantly increased both hepatic and muscular TG content at 0.5 and 5 mg/Kg/day doses. The plasma LMW ADP levels were significantly reduced only in the BPA high-dose (5 mg/Kg/day) group. |
| [57] | 10 μg/kg/day and 10 mg/kg/day |
Low and high | Diet | 2 weeks prior to mating (preconception) until weaning | C57BL/6 mice | M and F | ♂ Low BPA doses in the male offspring were associated with lower birth weights (PND 1) and the development of obesity in adulthood (PND 98 and117). ♂ Glucose tolerance test results (GTTs) were greater in high-dose (10 mg/kg/day) BPA male offspring than in control male offspring, consistent with the phenotype of glucose intolerance (PND 98 and 117). ♂ significantly increased insulin levels in the low-dose BPA group (PND 98 and 117). ♀ and ♂ Low and high doses of BPA had no effect on fasting glucose levels. Low- and high-dose BPA-exposed male but not female offspring had impaired glucose homeostasis and developed obesity in adulthood. |
| [53] | 50 µg/kg/day | Low | Oral gavage | GD 15–PND 21 | C3H/HeN mice | M | Low doses decreased gWAT at PND 45 and increased BW (PND 70 until PND 170). However, there was no effect on food intake, and it was associated with glucose intolerance (at PND 35) and decreased insulin sensitivity (at PND 125). |
| [54] | 0.5 or 50 µg/kg/day | Very low and low | Drinking water | GD 3.5–PND 22 | F344 rats | M and F | No effect on maternal parameters, including BW, food, and water intake. Increase in plasma TG with 50 µg/kg/day (♀) at 5 weeks and slightly increased BW at 52 weeks. Increase in plasma TG at 5 weeks in ♂ with 0.5 µg/kg BW/day offspring and low BW at 52 weeks. No effect on ♂ or ♀ offspring parameters, plasma TG, cholesterol, leptin, or ADP in BPA-exposed 52-week rat offspring. 5-week-old ♂ exposed to low doses (0.5 µg/kg /day) were linked with insulin resistance. |
| [46] | 10 μg/kg/day | Low | Subcutaneous injection | GD 9–GD 16 | OF-1 mice | M | Increased fasting blood glucose and higher insulin level (28 weeks), increased hepatic TG levels, and increased BW (PND 196). Increase in perigonadal fat pad weight at 28 weeks. |
| [48] | 1 and 10 µg/mL | Low | Drinking water | GD 6–PND 21 | SD rats | M | 1 µg/mL or 10 µg/mL BPA in water had no significant effect on maternal weight gain, food intake, or water consumption during pregnancy. For ♂ PND 7–PND 100, low-dose BPA (1 and 10 µg/mL) exposure increased BW. ♂ At puberty stage, a low dose (10 µg/mL BPA) increased blood glucose and insulin and decreased serum ADP. ♂At adult stage, both low doses increased blood glucose and insulin and significantly decreased the level of serum ADP. |
| [58] | 50 μg/kg/day | Low | Oral gavage | GD 0 until weaning at 3 weeks | Wistar rats | M | At week 3, a low dose had no effect on BW or blood glucose but increased the serum insulin level. At week 21, a low dose increased BW and insulin resistance and impaired glucose tolerance in rat’s hepatic tissue. |
| [26] | 1 and 20 µg/kg diet BPA |
Very low and low | Diet | Pregnant and lactating | CD-1 mice | M and F | Both low doses of BPA had no effect on maternal body weight or food intake or on the BW of 3-month-old (♂ and ♀) offspring. ♂ For adults, a low dose (20 µg/kg) impaired glucose tolerance and increased plasma insulin. However, no effect on leptin level was found. ♀ No effect on glucose tolerance and increased plasma leptin. |
| [59] | 10 or 100 µg/kg/day | Low and high | Subcutaneous | GD 9–GD 16 | OF-1 mice | M | A low BPA dose (10 µg/kg/day) displayed maternal glucose intolerance, and a high dose of BPA (100 µg/kg/day) showed a tendency to increase insulin sensitivity (but not statistically significant). Pregnant mice at GD 18 with exposure to BPA (100 µg/kg/day) showed significantly increased leptin, TG, and glycerol. At 3 months of age, for ♂ and ♀, both BPA doses had no effect on insulin resistance or glucose intolerance. At 6 months of age, male offspring exposed in utero had reduced glucose tolerance and increased insulin resistance (10 µg/kg/day). A low BPA (10µg/kg/day) dose decreased BW in the offspring. BPA (100 µg/kg/day) mice had higher levels of leptin than F0-BPA 10µg/kg/day mice. |
| [49] | 25 mg BPA/kg diet | High | Diet | GD 7.5–GD 18.5 | C57BL/6 mice | Foetus | A high dose of BPA (25 mg/kg) did not alter the expression of insulin in the foetal pancreatic islets. However, there was an increase in glucagon expression in BPA-exposed foetal pancreatic islets. |
| [60] | 100 µg/kg/day | High | Subcutaneous | GD 6–PND 0 PND 0–PND 21 GD 6–PND 21 |
C57BL6 mice | M and F | No effect on birth weight. ♂ and ♀ Showed significant decreases in the body weight of pups in the GD 6–PND 0 group. ♀ No differences in body weight were observed among the GD 6–PND 0, PND 0–PND 21, or GD 6–PND 21 groups from 3 to 35 weeks. However, GD 6–PND 0 mice started gaining less weight than controls from weaning until 35 weeks. ♂ The GD 6–PND 0 and PND 0–PND 21 groups increased BW, but the GD 6–PND 0 group had deceased BW. ♀ No effect on glucose tolerance in the PND 0–PND 21 or GD 6–PND 21 groups from 3 months to 8 months. PND 0–PND 21 male mice showed glucose intolerance. |
| [61] | 10 μg/kg/day and 10 mg/kg/day |
Low and high | Diet | 2 weeks prior to mating until weaning | C57BL/6J mice | M and F | High and low doses of BPA significantly impaired insulin secretion in male but not in female offspring. |
| [62] | 50 ng, 50 µg, or 50 mg BPA/kg | Very low, low, and high | Diet | 2 weeks prior to mating, pregnancy, and lactation | Mice | M and F | ♀ 50 ng and 50 mg of BPA/kg in the diet increased serum ADP levels in female adult offspring. ♂ Males exposed to 50 µg BPA/kg had marginally significant lower levels of ADP. ♀ 50 mg of BPA/kg in the diet decreased the mean baseline glucose and insulin levels. ♀ Significant decrease in insulin and the homeostasis assessment model of insulin resistance (HOMA-IR) levels but mildly lower serum glucose levels with 50 mg/kg in the diet in the female offspring. ♀ Significantly decreased serum leptin (50 mg BPA) but no effect in ♂. ♀ At 6 and 9 months of age, 50 ng BPA/kg-exposed females had an increase in fat mass and body weight compared with controls. ♂ No significant changes were found in fat mass in males. |
| [63] | 50 µg/kg/day | Low | Drinking water | GD 9–PND 21 | Wistar rats | M | Exposure to BPA (50 µg/kg/d) significantly increased BW with significantly greater amounts of epididymal and perirenal fat pads and increased food intake. BPA alone had no effect on fasting glucose or the glucose tolerance test, but BPA exposure of 50 µg/kg/day increased insulin and leptin levels. BPA impaired glucose homeostasis, induced obesity, and increased food intake in adult male rats. |
| [64] | 0.1 mg/L | Low | Drinking water | GD 11–PND 21 | SD rats | M | A low BPA dose had no effect on the food intake or water consumption of dams. BPA had no effect on BW of either dams or pups. A low BPA dose led to decreased glucose metabolism in rats. |
| [65] | 0.05, 0.5, or 5 mg/kg/day | Very low, low, and high | Subcutaneous injections | GD 30–GD 90 147 days |
Sheep | F | Prenatal-BPA-treated adult females were hyperglycaemic and had IR only at low BPA doses. |
| [66] | 2.5, 25, and 250 µg/kg/day | Very low, low, and high | Drinking water | Month virgin state plus 20 days during pregnancy | SD rats | M and F | BPA had no effect on the weight of pregnant rats or their plasma lipid profile (TC, TG, LDL, and HDL); sacrificed at GD 20. |
| [67] | 20 and 40 µg/kg/day |
Low | Orally by gastric intubation | GD 1 to GD 20 | Rats | Foetus | Increase in foetal serum leptin and insulin levels in both treated groups compared to controls. However, there was a decrease in maternal and foetal body weight in both treated groups compared to the control group. |
Male (♂); female (♀); triglyceride (TG); gestational day (GD); postnatal day (PND); bisphenol A (BPA); unesterified cholesterol (UC); very low-density lipoprotein (VLDL); total cholesterol (TC); high-density lipoprotein (HDL); low-density lipoprotein (LDL) was intraperitoneal glucose tolerance test (IPGTT); intraperitoneal insulin tolerance test (IPITT); body weight (BW); free fatty acid (FFA); adiponectin (ADP); and perigonadal white adipose tissue (gWAT).