The Effects of Different Concentrations of Retinoic Acid on the Histological Structure of Liver of Adult Albino Female Mice and Their Prenatal Fetuses

Barin Hussien Noori ,Intissar Numman Waheed

doi:10.7176/jbah/10-18-04

Abstract

Retinoic acid (RA) an active metabolite of vitamin A, plays essential signaling roles in mammalian embryonic development and adult homeostasis through concentration-dependent activity but in excess, RA is teratogenic. The present study was designed to evaluate the harmful effect of RA on the: liver tissues of the adult pregnant female albino mice and their prenatal fetuses and adult morphological and behavior changes. Forty-five pregnant adult female albino mice were divided into three groups (n=15 for each group). Group I, the control group orally received 0.1ml of olive oil. Group II and III received 25 and 50mg RA/kg B.W. respectively. RA was dissolved in 0.1ml of olive oil and orally given on 7 th , 8 th , and 9 th days of pregnancy. On the 18 th day of gestation, these females were sacrificed and the liver from mother and their prenatal were removed, weighed, and prepared for histological study. The RA treated adult group exhibited behavior changes including general fatigue and loss of appetite, in addition to the morphological changes which included weight loss, change in normal red eye color towards black, and redness in the mouth and chin area associated with loss of hair (fur) around this area. These observations were showed to be more severe in the 50 mg RA group. The results showed that treatment with 25 and 50mg RA caused no significant decrease in the adult liver weight, while in their prenatal fetuses 50mg RA caused a higher significant decrease in the liver weight, but 25 mg RA caused no significant effects on this weight. Treated with 50mg/kg RA caused a highly significant increase in the number of aborted and dead fetuses as compared with other groups. The results of the histological study showed that treatment with both concentrations of RA caused several degrees of the liver damage with disrupted the normal architecture pattern along with hepatocellular steatosis, hypertrophy, and inflammation. In conclusions, RA caused variable degrees of degeneration and destruction of the liver tissues of adult female (mother) and their prenatal. The most important effects of RA are causing hepatocellular steatosis, hypertrophy, and inflammation, and when RA giving during the critical periods of embryonic development, caused harmful effects on the developing liver, therefore treatment with RA should be avoided at any stage of gestation. Keywords: Liver, retinoic acid, embryonic development, vitamin A, histological study. DOI: 10.7176/JBAH/10-18-04 Publication date: September 30 th 2020

Highlights

Vitamin A and its physiologically active derivative, retinoic acid (RA), participate in many biological conditions, that control normal growth, embryo development, hormonic function, vision, reproduction, the maintenance and modulation of the immune feedbacks, and epithelial tissues and mucosa homeostasis (Cassani et al, 2012; Saeed et al, 2018; Haaker et al, 2020)
Two pre-cursor forms of vitamin A are obtained, retinol and retinyl ester from meat, and carotenoids (β-carotene, α-carotene, and β-cryptoxanthin) from plants. Both are metabolized into either RA or retinal which is the active metabolite of vitamin A, or they are stored as inactive retinyl esters in the liver or adipose tissue but to a lesser degree (Schreiber et al, 2012)
In the present study RA was given orally on 7th, 8th, and 9th days of gestation, these days as indicated by Rugh, (1968) and Stromland et al, (1991) are considered to be a critical time for organogenesis in mice, since liver diverticulum is reported to be formed by 9th days, and proliferates cells rapidly beginning of 9 1/2 days gestation shortly thereafter epithelial cords appear in the liver primordial (Rugh, 1968)

Summary

Introduction

Vitamin A and its physiologically active derivative, retinoic acid (RA), participate in many biological conditions, that control normal growth, embryo development, hormonic function, vision, reproduction, the maintenance and modulation of the immune feedbacks, and epithelial tissues and mucosa homeostasis (Cassani et al, 2012; Saeed et al, 2018; Haaker et al, 2020). Two pre-cursor forms of vitamin A are obtained, retinol and retinyl ester from meat, and carotenoids (β-carotene, α-carotene, and β-cryptoxanthin) from plants. Both are metabolized into either RA or retinal (retinaldehyde) which is the active metabolite of vitamin A, or they are stored as inactive retinyl esters in the liver or adipose tissue but to a lesser degree (Schreiber et al, 2012). The RA reacts with the retinoic acid receptor (RAR) and retinoic acid X receptor (RXR). both types encompass three isotypes (α, β, and γ) which affect transcription of several genes during vertebrate development (Linney et al, 2011; Kam et al, 2012)

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