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Impact of Melatonin on Full-Term Fetal Brain Development and Transforming Growth Factor-β Level in a Rat Model of Preeclampsia

  • Maternal Fetal Medicine/Biology: Original Article
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Abstract

Preeclampsia (PE) is a leading cause of stroke and cognitive impairment in the offspring. Melatonin is involved in the outcome of normal pregnancy. Its receptors are widespread in the embryo. This study aimed to investigate the fetal neuroprotective effect of melatonin in experimentally induced PE. After induction of pregnancy in 18 female rats, they were divided into three equal groups. PE was induced in groups II and III by injection of deoxycorticosterone acetate and drinking isotonic saline. Melatonin was supplied to group III orally (10 mg/kg body weight) throughout pregnancy. Pregnancy was terminated on day 20, and macroanatomical investigation of three fetuses from each pregnant rat and their placentae was performed. Placental and brain homogenates were analyzed for malondialdehyde (MDA), placental growth factor (PLGF), tumor necrosis factor-α (TNF-α), and brain transforming growth factor-β (TGF-β). Histopathological analysis of fetal brain sections was performed. Melatonin improved placental, fetal, and brain weight; significantly reduced fetal death rate; significantly increased PLGF, placental and brain superoxide dismutase, and brain TGF-β; and significantly decreased placental TNF-α and brain MDA. Brain micromorphological study found normal glial cells and neuropil in the melatonin-treated group and a loss of neuronal cell outlines with an accumulation of cellular debris in the untreated group. In conclusion, melatonin approximately showed a neuroprotective activity by managing PE-induced oxidative stress in the placenta and fetal cerebral cortex of rats.

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Funding

The Ministry of High Education and Scientific Research and Zagazig University, Egypt, supported this work by supplying the required kits, chemicals, and tools. All experiments were performed at Zagazig University laboratories.

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Authors and Affiliations

  1. Physiology Department, Faculty of Medicine, Zagazig University, Al Sharqiya, Egypt

    Nanees Fouad El-Malkey & Sama Salah Khalil

  2. Anatomy and Embryology Department, Faculty of Veterinary Medicine, Zagazig University, Al Sharqiya, Egypt

    Mohammed Aref & Hassan Emam

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  1. Nanees Fouad El-Malkey
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  2. Mohammed Aref
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  3. Hassan Emam
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  4. Sama Salah Khalil
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Contributions

All authors contributed to the conception and design of the study. Material preparation, data collection, and analysis were performed by Dr. Nanees F. El-Malkey, Dr. Mohammed Aref, Dr. Hassan Emam, and Dr. Sama Salah Khalil. The first draft of the manuscript was written by Dr. Nanees F. El-Malkey, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Nanees Fouad El-Malkey.

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El-Malkey, N.F., Aref, M., Emam, H. et al. Impact of Melatonin on Full-Term Fetal Brain Development and Transforming Growth Factor-β Level in a Rat Model of Preeclampsia. Reprod. Sci. 28, 2278–2291 (2021). https://doi.org/10.1007/s43032-021-00497-3

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