Summary
BPA is a synthetic estrogen used in production of polycarbonate plastics, epoxy resins, dental sealants and thermal receipt paper . Epoxy resins are used as coating materials for food cans and metal lids, whereas polycarbonate is used in manufacture of house hold appliances, food packaging materials , plastic bottles , baby bottles and many other products. Incomplete polymerization of BPA leads to its leakage and subsequent human oral exposure. Humans are also exposed to BPA through inhalation and absorption through the skin and oral mucous membrane.
This work was aimed to investigate the toxic effects of prenatal exposure of BPA on the rats prostate and mammary glands at ages of 1, 3, 5 months after birth and to investigate the possible protective effects of indole-3-carbinol ( I3C) on these toxic effects. Also this work was aimed to assay the serum testosterone and estrogen levels in the studied groups.
40 adult pregnant female albino rats were used in this study. The
pregnant rats were divided equally into five groups:
1- Negative control group:8 rats did not receive any medication.
2- positive control group: 8 rats received the solvent , canola oil orally by gavage in dose of 1 ml /kg body weight (bw) once daily from 8th day of pregnancy up to day 21.
3- Indole group : 8 rats received 2 g indole 3 carbinol / kg chow once daily from 8th day of pregnancy up to day 21.
4- Bisphenol group: 8 rats were subdivided equally into two subgroups:
Subgroup (4 a) :4 rats received 1 ml / kg bw from the solution with concentration of 25 μg of BPA /ml , orally by gavage once daily from 8th day of pregnancy up to day 21.
Subgroup (4b):4 rats received 1 ml / kg bw from the solution with concentration of 250 μg of BPA /ml , orally by gavage once daily from 8th day of pregnancy up to day 21.
5- Bisphenol and indole group: 8 rats were subdivided equally into two subgroups:
Subgroup (5a):4 rats received 1 ml / kg bw from the solution with concentration of 25 μg of BPA /ml , orally by gavage once daily , plus 2 g indole 3 carbinol / kg chow from 8th day of pregnancy up to day 21.
Subgroup (5b):4 rats received 1 ml / kg bw from the solution with concentration of 250 μg of BPA /ml , orally by gavage once daily , plus 2g indole 3 carbinol /kg chow from 8th day of pregnancy up to day 21.
After labour, pups were left with lactating mothers for 2 weeks. Then they were separated from their mothers until day of sacrification at 1 , 3 and 5 months after birth. After the experiment the rats of each group were subdivided into 3 subgroups:
The 1st subgroup was killed at 1 month after birth.
The 2nd subgroup was killed at 3 months after birth.
The 3rd subgroup was killed at 5 months after birth.
The rats of each group were anaesthetized then blood samples were taken from the right ventricle by sterile syringes for biochemical analysis of testosterone of male rats and estrogen in female rats. Then the prostate and mammary gland specimens were collected and prepared for light and electron microscopic analysis.
In the present study, the prostates of the control groups were formed of acini lined by simple columnar epithelium with basal rounded nuclei and the interstitial space showed scanty collagen fibers. Ultrastructurally , the cells contained normal mitochondria , Golgi apparatus and rough endoplasmic reticulum. But the prostates of BPA treated groups revealed the following changes. There were epithelial hyperplasia , increased intraluminal papillary projections , congested blood vessels in the interstitial space , sloughing of acinar epithelium (with high dose only) and increased amount of collagen fibers around the acini ( more in high dose). Also there were vacuolated cytoplasm in epithelial cells at ages of 1 and 3 months. Thick fibromuscular stroma around the prostatic acini aged 1 month. The interstitial space presented inflammatory cells at age of 1 month with both doses of BPA and at 5 months with high dose.
The ultrastructural examination of prostates from BPA treated groups revealed epithelial hyperplasia with multiple levels of heterochromatic nuclei of different sizes and irregular shapes , vacuolated mitochondria and loss of microvilli from the luminal surface of the cells. There were also , cytoplasmic vacuoles at ages of 1 and 3 months and dilated rough endoplasmic reticulum and Golgi apparatus at ages of 3 and 5 months.
In the present study , the prostates from bisphenol and indole treated groups showed nearly healthy simple columnar epithelium with basal regular nuclei and intact organelles. The interstitial space showed normal amounts of collagen fibers.
In the present study , the mammary glands of control groups were formed of ducts lined by low columnar epithelium . The ducts were surrounded by scanty stroma and collagen fibers and were embedded in fatty connective tissue. While the mammary glands of treated groups showed epithelial hyperplasia in the ducts. There were detached epithelial cells accumulating inside the lumen. The dusts were surrounded by dense fibromuscular stroma and markedly increased amount of collagen fibers and were embedded in fibrofatty connective tissue. The mammary glands of rats aged 5 months old and treated by high dose showed epithelia hyperplasia in the cribriform pattern, while those of rats treated by low dose showed congested blood vessels in the connective tissue around the ducts.
In the present study , the mammary glands treated with BPA and I3C showed nearly healthy ducts lined by low columnar epithelial cells with mostly normal structure. The ducts were surrounded by scanty to moderate stroma.
In the present study, the differences in serum levels of testosterone and estrogen were not statistically significant among the experimental groups.
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