Ovarian development in Wistar rat treated prenatally with single dose diisobutyl phthalate

Abstract

Abstract:Phthalates are a class of industrial compounds with an array of toxicological properties used in day to day life. Diisobutyl phthalate on (DIBP) is used as an additive to keep the plastics soft or fl exible (plasticizer) in nitrocellulose plastic, nail polish, explosives, lacquer manufacturing etc. Although DIBP exposure in humans is generally low, people in adhesive industries and pharmaceutical industries are exposed to higher levels. The aim of this study was to determine the effect of single dose of DIBP on developing ovary of Wistar rat. One hundred and eight adult pregnant Wistar rats were divided into control and experimental groups. Rats in experimental group were given DIBP on day 10, 12 and 14 of gestation at 0.375, 0.75 and 1.25 ml/kg body weight dose intraperitoneally in a single dose. Sections of ovaries collected on day 21 of gestation were stained with hematoxylin and eosin and examined and Masson's trichrome histologically. Sections belonging to the control group showed the presence of oocytes in clusters separated by thin fi brous septa. Degeneration oocytes, empty follicles surrounded by follicular cells without gonocytes in the center were observed in ovarian stroma. Blood vessels in the ovarian stroma were prominent and congested. Around a bunch of follicles total architectural disarray was observed although on special staining fi brosis was not evident. As pregnant women are constantly exposed, effect of DIBP on ovary of a developing fetus would denote the long term consequence in future generations (Fig. 5, Ref. 39 Phthalates are a class of widely used industrial compounds known technically as dialkyl or alkyl aryl esters of 1, 2-benzenedicarboxylic acid. The common forms of phthalates are Diethyl hexyl phthalate (DHEP), Diallyl phthalates (DAP), Di-n-propyl phthalates (DPP), Di-n-butyl phthalates (DBP), and Diisobutyl phthalates (DIBP).Phthalates with a variety of toxicological properties are used in day to day life. These phthalates are nearly omnipresent in modern society and are found in the plastic items, vinyl fl ooring, wall coverings, lubricants, adhesives, detergents, nail polish, hair spray and car wash (1).The adverse effects produced by phthalates are changes in morphology, physiology, growth, development or life span of an organism which results in an impairment of functional capacity and ability to compensate for additional stress (2). Diisobutyl phthalateDIBP (phthalic acid ,di isobutyl ester 1,2-benzenedicarboxylic acid ,bis-(2-methyl propyl) ester di-(isobutyl)-1,2-benzene dicarboxylate) is the branched isomer of DBP and an additive used to keep the plastics soft or more fl exible (plasticizer) often in combination with other phthalates. DIBP is used in nitrocellulose plastic, nail polish, explosive materials, lacquer manufacturing, consumer products, blood bags, pharmaceuticals and automobile parts. They are ubiquitous in our environment and most people including pregnant women and their fetuses are exposed to multiple phthalates at a time. Saillenfait et al estim...

Hazards of diisobutyl phthalate (DIBP) exposure: A systematic review of animal toxicology studies

“…Of these, 25 met the defined PECO criteria for inclusion and were moved forward for study evaluation. The studies excluded after full text screening were all animal toxicology studies that did not meet PECO criteria, consisting of three studies that used intraperitoneal injection ( Lawrence et al, 1975 ; Ray et al, 2012 ; Singh et al, 1972 ), two studies in nonmammalian species [chickens: Choy, 1975 ; zebrafish: Sohn et al, 2016 ], and one behavioral study in mice ( Ma et al, 2013 ). Additionally, the included article by University of Rochester (1954) presented data from multiple experiments, including a rat study that complied with the PECO criteria and was moved forward for study evaluation, and a dog study and several acute studies that were rejected for not meeting the PECO criteria.…”

The Effects of Phthalates on the Ovary

“…Interestingly, the decrease in oocyte DNA methylation of Igf2r and Peg3 is also evident in the oocytes of the F2 offspring, suggesting that the effects of DEHP on oocyte development are heritable ( 115 ). Gestational exposure to a single intraperitoneal injection of DIBP resulted in architectural disarray of follicles in fetal rats ( 116 ). Specifically, DIBP exposure at 0.375–1.25 ml/kg increased the numbers of degenerated oocytes and empty follicles without oocytes, and the blood vessels located in the stroma of the ovary appeared prominent and congested ( 116 ).…”

“…Gestational exposure to a single intraperitoneal injection of DIBP resulted in architectural disarray of follicles in fetal rats ( 116 ). Specifically, DIBP exposure at 0.375–1.25 ml/kg increased the numbers of degenerated oocytes and empty follicles without oocytes, and the blood vessels located in the stroma of the ovary appeared prominent and congested ( 116 ). MEHP has also been shown to affect ovarian development in the human.…”

“…Interestingly, oocyte numbers were not affected by MEHP treatment, but the same study suggests that phthalate toxicity to the developing human ovary may be mediated by nuclear receptor signaling ( 117 ). It appears that phthalates disrupt early ovarian and oocyte development potentially leading to oocyte death and abnormal ovarian architecture ( 112 , 113 , 116 ). The mechanisms by which phthalates alter the earliest stages of ovarian development appear to include an anti-estrogenic response ( 112 ), an increase in oxidative stress ( 113 ), and heritable modifications to the oocyte epigenome ( 115 ).…”

Ендокринні Дизраптори — Пренатальні Чинники Розладів Репродуктивного Здоров’я

“…Пренатальні ефекти фталатів на розвиток репродуктивної системи нащадків жіночої статі досліджені значно менше. Ray B. et al показали, що інтраперитоніальне введення діізобутилфталату на 10-й, 12-й та 14-й дні вагітності в дозах 375, 750 та 1250 мкг/кг порушує морфологію яєчників у дорослих нащадків [38]. Натомість в іншій роботі не виявлено впливу експозиції щурів до ДБФ у дозах 10, 100 або 600 мг/кг під час гестації та лактації на статевий розвиток, масу яєчників і матки та естральну циклічність, проте показано підвищення рівнів естрадіолу та прогестерону в нащадків, матері яких отримували ДБФ у найнижчій дозі, що може вплинути на фертильність щурів потомства першої генерації [39].…”