Article
Melatonin preserves ovarian tissues
of rats exposed to chronic TCDD:
An electron microscopic approach
to effects of TCDD on ovarian cells
Semir Gu¨ l, Mehmet Gu¨ l and Birgu¨ l Yigitcan
Abstract
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a toxic agent and has disruptive effects on reproductive tis-
sues in females. TCDD disrupts the hormonal regulation of the body and decreases the production of mel-
atonin. In this study, we investigated the protective effects of melatonin supplements against the toxic effects of
TCDD on ovaries of female rats. TCDD caused a significant decrease in the average number of corpora lutea
and follicles per tissue section (2.1 + 0.7; 2.3 + 0.8, respectively), whereas these numbers were maintained in
the melatonin supplemented group (5.0 + 0.8; 5.1 + 0.8, respectively) and were similar to the control group
(5.3 + 1.0; 5.9 + 0.9, respectively). Electron microscopic analysis showed that the disruption of ultrastructure
components such as cell membrane and organelles due to TCDD exposure was inhibited by melatonin sup-
plements. This study suggested that melatonin has a protective and a possible ameliorative effect over his-
topathological damage of rat ovaries exposed to TCDD.
Keywords
2,3,7,8-Tetrachlorodibenzo-p-dioxin, ovary, melatonin, rat, dioxins
Received 23 August 2017; Revised 25 September 2017; Accepted 11 December 2017
Introduction
2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD), the
most toxic member of the halogenated aromatic
hydrocarbons, is a prevalent and persistent environ-
mental contaminant formed as a synthesis side
product of herbicides production and overuse of
herbicides, waste incineration and combustion
processes, paper bleaching, and the manufacture of
plastics (Jun et al., 2011; Poland and Knutson,
1982; Yoshizawa et al., 2007). This toxic agent is able
to pass from environment to humans through the food
chain by absorption by the gastrointestinal system
(Hutz, 1999). TCDD has a variety of adverse biologi-
cal effects, including carcinogenesis, immune and
hematopoietic dysfunction, neuronal cell damage
(Aylward et al., 2005; Baldridge et al., 2015; Cole
et al., 2003), developmental defects, impairment ovu-
lation, and fertility reduction (Kakeyama and
Tohyama, 2003). TCDD is classified as an endo-
crine-disturbing compound by altering endocrine
hormone synthesis (Kakeyama and Tohyama, 2003;
Linden et al., 1991).
Experimental data indicated that melatonin is one
of these endocrine hormones targeted by TCDD, and
its production decreased dramatically and consider-
ably in rats upon TCDD exposure (Pohjanvirta
et al., 1996). Melatonin, chemically N-acetyl-
5-methoxy tryptamine, is primarily produced by the
pineal gland in humans and acts as an endocrine hor-
mone by passing into the blood circulation (Hardeland
et al., 2006). It exhibits numerous physiological and
metabolic functions such as an antioxidant, circadian
Department of Histology and Embryology, Faculty of Medicine,
_
Ino¨nu¨ University, Malatya, Turkey
Corresponding author:
Semir Gu¨l, Department of Histology and Embryology, Faculty of
Medicine,
_
Ino¨nu¨ University, Malatya 44280, Turkey.
Email: semir.gul@inonu.edu.tr
Toxicology and Industrial Health
1–9
© The Author(s) 2018
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DOI: 10.1177/0748233717754174
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