The Influence of Prenatal Fumonisin Exposure on Bone Properties, as well as OPG and RANKL Expression and Immunolocalization, in Newborn Offspring Is Sex and Dose Dependent.

Ewa Tomaszewska,Ihor Kotsyumbas,Volodymyr Kushnir,Janine Donaldson,Oksana Brezvyn,Izabela Świetlicka,Monika Hułas-Stasiak,Viktor Muzyka,Marta Arczewska,Siemowit Muszyński,Piotr Dobrowolski,Halyna Rudyk,Iwona Puzio

doi:10.3390/ijms222413234

Abstract

The current study examined the effects of exposure of pregnant dams to fumonisins (FBs; FB1 and FB2), from the seventh day of pregnancy to parturition, on offspring bone metabolism and properties. The rats were randomly divided into three groups intoxicated with FBs at either 0, 60, or 90 mg/kg b.w. Body weight and bone length were affected by fumonisin exposure, irrespective of sex or dose, while the negative and harmful effects of maternal FBs’ exposure on bone mechanical resistance were sex and dose dependent. The immunolocalization of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-Β ligand (RANKL), in bone and articular cartilage, indicated that the observed bone effects resulted from the FB-induced alterations in bone metabolism, which were confirmed by the changes observed in the Western blot expression of OPG and RANKL. It was concluded that the negative effects of prenatal FB exposure on the general growth and morphometry of the offspring bones, as a result of the altered expression of proteins responsible for bone metabolism, were dose and sex dependent.

Highlights

Besides the delivery of vitally important nutrients, the diet is a source of other components, sometimes toxic ones, which make their way into the diet especially under favorable climatic conditions
The intensity and immunolocalization of the OPG and receptor activator of nuclear factor kappa-B ligand (RANKL) reactions in the rats in the current study showed that this balance does not always occur in all areas of the bone, the overall expression could be considered as in balance
Our study showed that the male newborn rats were unaffected by the mycotoxins, irrespective of the FBs’ dose, as the intensity of the cartilage oligomeric matrix protein (COMP) immunoreaction was significantly weaker compared to that observed in the control group, while the percentage of COMPpositive chondrocytes increased with FBs’ dose in the female newborns, with the intensity of the COMP immunoreaction being highest in the 60 mg/kg b.w

Summary

Introduction

Besides the delivery of vitally important nutrients, the diet is a source of other components, sometimes toxic ones, which make their way into the diet especially under favorable climatic conditions. Under such conditions, the feed can be contaminated with fungi like Fusarium, which produces mycotoxins as secondary products of its metabolism. The feed can be contaminated with fungi like Fusarium, which produces mycotoxins as secondary products of its metabolism Pigs, sheep, and rodents are more sensitive to FBs than other animals and display non-species-specific symptoms like hepatic or kidney toxicity [8,9,10,11]. FBs have been shown to be hepatocarcinogenic in rats and mice, and they have been shown to disturb the intestinal barrier even at a very low dose of 1.0 mg/kg b.w. [13,14]

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