Expression of Metallothioneins in Placental and Fetal Tissues in Undisturbed and PGM-Zn Treated Syngeneic Pregnancy

Abstract

Metallothioneins (MTs) are cysteine-rich proteins, which have been implicated in regulation of physiological processes, such as cell growth, repair, differentiation, apoptosis and immunoregulation, as well as in the protection against heavy metals, oxidant damages, inflammation and other stressful conditions. To investigate their roles in physiological and detoxification processes at the maternal-fetal interface and in fetal organogenesis we examined the tissue expression of MT I/II isoforms in undisturbed syngeneic pregnancy and after the treatment with peptidoglycan monomer linked with zinc (PGM-Zn). The data showed that in undisturbed pregnancy the MTs were highly expressed at junctional zone of placenta, on endovascular trophoblast giant cells, glycogen cells and spongiotrophoblast cells, as well as on villous trophoblast cells. In the fetus they were found predominantly in the liver and in epithelial tissues, such as intestine, pancreas and kidney. Treatment with PGM-Zn markedly enhanced the intensity of MT staining both at the maternal-fetal interface and in fetal organs. The data imply that MTs are involved in the protection of trophoblast cells against the pregnancy-induced deregulation of redox and neuro-immuno-endocrine homeostasis, in transport and storage of essential metals required for fetal organogenesis, as well as in the protection of fetus against bacterial toxins.

Reproductive immunology in viviparous mammals: evolutionary paradox of interactions among immune mechanisms and autologous or allogeneic gametes and semiallogeneic foetuses

“…The treatment with the PGM-Zn preparation markedly enhanced the intensity of MT tissue expression in placenta and trophoblast cells, and particularly in the foetal organs. The data imply that MT are involved in the protection of trophoblast cells against the pregnancy-induced deregulation of redox and neuro-immuno-endocrine homeostasis, in transport and storage of essential metals required for foetal organogenesis, as well as in the protection of foetus against bacterial toxins (Jakovac et al 2015). Knowledge about a vast variety of natural (endogenous and exogenous) or synthetic substances with immunomodulatory properties which may act as IM to A c c e p t e d M a n u s c r i p t maintain an optimally effective, but not excessive and harmless innate and adaptive immune responses to foetal and trophoblast antigens is crucial in order to develop an efficient immune therapy to patients with previous early and late pregnancy complications.…”

Toxic Effects of Zinc Chloride on the Bone Development in Danio rerio (Hamilton, 1822)

“…The inhibition of DNA synthesis is the most likely explanation of Zn teratogenicity but the specific mechanism is unknown (Jakovac et al, 2015 ). Some authors affirmed that in mammals an excessive amount of zinc chloride is little teratogenic to due to protective mechanisms of the maternal liver and metalloenzymes (Küçükoğlu et al, 2013 ), while for a oviparous aquatic organisms, not having no protection, an excessive amount of zinc chloride may cause an abnormal development (Nagel, 2002 ).…”

Genomic biomarkers of prenatal intrauterine inflammation in umbilical cord tissue predict later life neurological outcomes

“…Similarly, the protein domains that were significantly enriched among the genes with increased expression in association with one or more histological marker of intrauterine inflammation were small cytokines, metallothionein, and S-100/ ICaBP type calcium binding domain. Proteins containing all of these domains have been demonstrated to play a role in placental inflammation [ 33 – 35 ]. Interestingly, elevated levels of interleukin-8 (IL-8) in cord blood have been previously associated with a higher incidence with brain injury in preterm infants with placental inflammation [ 35 ].…”