Abstract
Of late, a consirable interest has grown in literature on early development of arsenicosis and untimely death in humans after exposure to iAs in drinking water in utero or during the childhood. The mechanism of this kind of intrauterine arsenic poisoning is not known; however it is often suggested to involve stem cells. We looked into this possibility by investigating in mice the influence of chronic in utero exposure to arsenical drinking water preliminarily on multipotent adult stem cell and progenitor cell counts at the beginning of neonatal age. We found that repeated intake of 42.5 or 85ppm iAs in drinking water by pregnant BALB/c mice substantially changed the counts of EpASCs, the progenitor cells, and the differentiated cells in epidermis of their zero day old neonates. EpASCs counts decreased considerably and the differentiated / apoptosed cell counts increased extensively whereas the counts of progenitor cell displayed a biphasic effect. The observed trend of response was dose-dependent and statistically significant. These observations signified a disruption in stem cell homeostasis. The disorder was in parallel with changes in expression of biomarkers of stem cell and progenitor (TA) cell besides changes in expression of pro-inflammatory and antioxidant molecules namely Nrf2, NFkB, TNF-α, and GSH. The biological monitoring of exposure to iAs and the ensuing transplacental toxicity was verifiable correspondingly by the increase in iAs burden in hair, kidney, skin, liver of nulliparous female mice and the onset of chromosomal aberrations in neonate bone marrow cells. The combined intake of selenite and curcumin in utero was found to prevent the disruption of homeostasis and associated biochemical changes to a great extent. The mechanism of prevention seemed possibly to involve (a) curcumin and Keap-1 interaction, (b) consequent escalated de novo GSH biosynthesis, and (c) the resultant toxicant disposition. These observations are important with respect to the development of vulnerability to arsenicosis and other morbidities later in life after repeated in utero or postnatal exposure to iAs in drinking water that may occur speculatively through impairment of adult stem cell dependent innate tissue repair mechanism.
Highlights
Of late, a considerable interest has grown in literature on early development of arsenicosis as well as untimely mortality later in human life after repeated exposure to arsenical drinking water in utero and during the childhood
At 42.5ppm Inorganic arsenic (iAs) dose (Fig 1B), total yield of label-retaining keratinocytes (LRKs) increased to 80.78% whereas at 85ppm iAs dose, the yield decreased to 42.24% (Fig 1C)
This study demonstrated that repeated in utero exposure to arsenical drinking water influenced adult stem cell homeostasis in neonate epidermis at the time of birth by inducing a significant change in counts of Epidermal adult stem cells (EpASCs), unipotent / progenitor transiently amplifying (TA) cells, and differentiated cells along with the alterations in levels of Nuclear factor-like 2 (Nrf2), nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB), Inhibitor of NF-κB activity (IkB), tumor necrosis factor alpha (TNF-α) protein products and GSH
Summary
A considerable interest has grown in literature on early development of arsenicosis as well as untimely mortality later in human life after repeated exposure to arsenical drinking water in utero and during the childhood. The optimum numbers are considered to be necessary for the tissue growth during embryogenesis as well as in wound repair both in utero and in postnatal stages [16] In view of this tacit information, it is reasonable to believe that the manipulation of stem cell numbers by chronic exposure to iAs in utero or in postnatal age could disorder the optimal dynamics of EpASC homeostasis in tissues and eventually the organ growth. This plausibility has seldom been explored [17,18,19,20]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
