Transplacental exposure to arsenic disrupts offspring metabolism through sex specific pathological changes in liver and adipose tissue

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Shagun Shukla, Siddhartha Gangopadhyay, Anchal Chauhan, Deepak Chand Sharma, Vikas Srivastava

Abstract

Background: Suboptimal fetal environment may cause pathological and functional changes in the adulthood and may impact health and metabolism of the offspring. Transplacental exposure to environmentally relevant doses of arsenic may program offspring metabolism through alterations in the development of major metabolic organs such as kidneys, liver and adipose tissue. Alterations particularly in the liver and adipose tissue may cause altered glucose homeostasis and insulin sensitivity in the offspring.


 


Methods:  Female Balb/c mice were exposed to environmentally relevant doses of arsenic (0, 0.04 and 0.4 mg/kg) from 15 days prior to conception until delivery. The offspring were divided according to sex and monitored for metabolic alterations, particularly glucose homeostasis was monitored by periodically checking for fasting glucose levels and metabolic tolerance tests. Pathological changes in major metabolic organs i.e., liver, inguinal white adipose tissue and kidneys were observed by standard pathological staining process.


 


Results: Adult female offspring showed marked increase in the weight gain pattern and relative adiposity owing to fat deposition in the inguinal fat depot was also found to be increased. Transplacental exposure to arsenic correlated with a marked decrease in insulin sensitivity and glucose tolerance. As the liver and adipose tissue dictates whole body insulin resistance, we checked any pathological alterations in these organs. Adipocyte hypertrophy marked by a substantial increase in cellular volume was seen in the treated groups. the liver showed micro and macro vesicular fatty changes with necrotic foci which were apparent in the female offspring. The kidneys showed minor glomerular swelling and mesangial cell infiltration showing inflammatory changes in the organ.


 


Conclusion: Transplacental exposure to arsenic may alter metabolic phenotype in the adulthood leading to dysfunction and pathological outcomes in major metabolic organs.

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