scholarly journals Impaired Morphogenesis and Function of Rat Adrenal Zona Glomerulosa by Developmental Low-Dose Exposure to DDT Is Associated with Altered Oct4 Expression

2021 ◽  
Vol 22 (12) ◽  
pp. 6324
Author(s):  
Nataliya V. Yaglova ◽  
Sergey S. Obernikhin ◽  
Dibakhan A. Tsomartova ◽  
Svetlana V. Nazimova ◽  
Valentin V. Yaglov ◽  
...  
Keyword(s):  
Postnatal Development ◽  
Low Dose ◽  
Organic Pollutant ◽  
Endocrine Disrupting Chemicals ◽  
Zona Glomerulosa ◽  
Low Doses ◽  
Hormone Production ◽  
Functional Changes ◽  
And Function ◽  
The Impact

Dichlorodiphenyltrichloroethane (DDT) is a persistent organic pollutant and one of the most widespread endocrine disrupting chemicals. The impact of low-dose exposure to DDT on the morphogenesis of the adrenal gland is still poorly understood. The development and function of zona glomerulosa in rats has been found to be associated with changes in the expression of the transcription factor Oct4 (Octamer 4), which is the most important player in cell pluripotency. The aim of the study was to investigate the morphogenesis and function of rat adrenal zona glomerulosa in rats exposed to low doses of DDT during prenatal and postnatal development and to determine the possible role of Oct4 in DDT-mediated structural and functional changes. The DDT-exposed rats demonstrated slower development and lower functional activity of the zona glomerulosa during the pubertal period associated with higher expression of Oct4. Further, accelerated growth and restoration of hormone production was associated with, firstly, a decrease in Oct4 expressing cells and secondly, the loss of the inverse relationship between basal aldosterone levels and the number of Oct4 expressing cells. Thus, the transcriptional factor Oct4 exhibited an altered pattern of expression in the DDT-exposed rats during postnatal development. The results of the study uncover a novel putative mechanism by which low doses of DDT disrupt the development of adrenal zona glomerulosa.

Neuroimmune interactions and pain during postnatal development

2013 ◽  
pp. 65-73
Author(s):  
David Vega-Avelaira ◽  
Simon Beggs
Keyword(s):  
Postnatal Development ◽  
Immune Cells ◽  
Defensive Responses ◽  
Nociceptive Pathways ◽  
Neuroimmune Interactions ◽  
The Central Nervous System ◽  
And Function ◽  
Type Of Injury ◽  
The Impact ◽  
Role And Function

The immune system is essential for identifying and mounting defensive responses to tissue damage and infection. In addition, it is increasingly recognized that interactions between immune cells and nociceptive pathways can modulate pain sensitivity. The role and function of immune cells in the central nervous system changes during postnatal development, and as a result, the impact of neuroimmune interactions on pain signalling varies with both age and the type of injury.

scholarly journals Perinatal Exposure to Phthalates: From Endocrine to Neurodevelopment Effects

2021 ◽  
Vol 22 (8) ◽  
pp. 4063
Author(s):  
Laura Lucaccioni ◽  
Viola Trevisani ◽  
Erica Passini ◽  
Beatrice Righi ◽  
Carlotta Plessi ◽  
...  
Keyword(s):  
System Development ◽  
Endocrine Disrupting Chemicals ◽  
Cognitive Disorders ◽  
Perinatal Exposure ◽  
Adverse Health Outcomes ◽  
Endocrine Disrupting ◽  
And Function ◽  
The Impact ◽  
Temporal Windows

Phthalates, as other endocrine disrupting chemicals (EDCs), may alter the homeostasis and the action of hormones and signaling molecules, causing adverse health outcomes. This is true especially for infants, who are both more exposed and sensitive to their effects. Phthalates are particularly harmful when the exposure occurs during certain critical temporal windows of the development, such as the prenatal and the early postnatal phases. Phthalates may also interfere with the neuroendocrine systems (e.g., thyroid hormone signaling or metabolism), causing disruption of neuronal differentiation and maturation, increasing the risk of behavioral and cognitive disorders (ADHD and autistic behaviors, reduced mental, psychomotor, and IQ development, and emotional problems). Despite more studies being needed to better understand the role of these substances, plenty of evidence suggests the impact of phthalates on the neuroendocrine system development and function. This review aims to update the knowledge on the neuroendocrine consequences of neonatal and perinatal exposure to phthalates.

scholarly journals Acrylamide-induced changes of granulopoiesis in porcine bone marrow

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Dominika Grzybowska ◽  
Anna Snarska
Keyword(s):  
Bone Marrow ◽  
Cell Morphology ◽  
Light Microscope ◽  
Low Dose ◽  
Low Doses ◽  
Cytological Evaluation ◽  
High Doses ◽  
Induced Changes ◽  
The Impact ◽  
Experimental Group

Abstract Introduction Due to the widely documented and diverse toxic effects of acrylamide, the authors decided to evaluate the impact of high and low doses of this compound on the process of granulopoiesis in porcine bone marrow. Material and Methods The experiment was conducted on 15 Danish Landrace pigs at the age of 8 weeks. The animals were randomly assigned into three equal groups (n = 5). Control animals received empty gelatine capsules as placebo. Animals in the first experimental group (the LD group) received a low dose of acrylamide of 0.5 μg/kg b.w./day, and animals in the second experimental group (the HD group) received a tenfold higher dose of acrylamide of 5 μg/kg b.w./day. Placebo and acrylamide capsules were administered with feed every morning for 28 days. Bone marrow was collected into tubes without an anticoagulant twice – before the first capsule administration (day 0) and on the 28th day of the study. After drying and staining, bone marrow smears were subjected to detailed cytological evaluation under a light microscope. Results Changes in cell morphology, i.e. degenerative changes in the cellular nuclei, were observed in both experimental groups. Both low and high doses of acrylamide decreased the number of segmented eosinophils, neutrophilic and segmented metamyelocytes, neutrophils, as well as basophils and basophilic metamyelocytes. Conclusion Acrylamide at doses of 0.5 μg/kg b.w./day and 5 μg/kg b.w./day clearly influences porcine granulopoiesis.

scholarly journals Low-Dose Pesticides Alter Primary Human Bone Marrow Mesenchymal Stem/Stromal Cells through ALDH2 Inhibition

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5699
Author(s):  
Amélie Foucault ◽  
Noémie Ravalet ◽  
Joevin Besombes ◽  
Frédéric Picou ◽  
Nathalie Gallay ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Low Dose ◽  
Low Doses ◽  
Aldehyde Dehydrogenase 2 ◽  
Primitive Hematopoiesis ◽  
In Vitro Effects ◽  
High Doses ◽  
Chlorpyrifos Ethyl ◽  
The Impact

(1) Background: The impact of occupational exposure to high doses of pesticides on hematologic disorders is widely studied. Yet, lifelong exposure to low doses of pesticides, and more particularly their cocktail effect, although poorly known, could also participate to the development of such hematological diseases as myelodysplastic syndrome (MDS) in elderly patients. (2) Methods: In this study, a cocktail of seven pesticides frequently present in water and food (maneb, mancozeb, iprodione, imazalil, chlorpyrifos ethyl, diazinon and dimethoate), as determined by the European Food Safety Authority, were selected. Their in vitro effects at low-doses on primary BM-MSCs from healthy volunteers were examined. (3) Results: Exposure of normal BM-MSCs to pesticides for 21 days inhibited cell proliferation and promoted DNA damage and senescence. Concomitantly, these cells presented a decrease in aldehyde dehydrogenase 2 (ALDH2: mRNA, protein and enzymatic activity) and an increase in acetaldehyde levels. Pharmacological inhibition of ALDH2 with disulfiram recapitulated the alterations induced by exposure to low doses of pesticides. Moreover, BM-MSCs capacity to support primitive hematopoiesis was significantly altered. Similar biological abnormalities were found in primary BM-MSCs derived from MDS patients. (4) Conclusions: these results suggest that ALDH2 could participate in the pathophysiology of MDS in elderly people long exposed to low doses of pesticides.

scholarly journals Secretion of adrenal zona glomerulosa cells in rats exposed to low doses of dichlorodiphenyltrichloroethane during prenatal and postnatal development

2018 ◽  
Vol 7 (3) ◽  
pp. e0302
Author(s):  
Dibakhan A. Tsomartova ◽  
Natalia V. Yaglova ◽  
Sergey S. Obernikhin ◽  
Svetlana V. Nazimova ◽  
Valentin V. Yaglov
Keyword(s):  
Postnatal Development ◽  
Zona Glomerulosa ◽  
Low Doses ◽  
Glomerulosa Cells ◽  
Prenatal And Postnatal Development ◽  
Zona Glomerulosa Cells

scholarly journals Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses

2012 ◽  
Vol 33 (3) ◽  
pp. 378-455 ◽  
Author(s):  
Laura N. Vandenberg ◽  
Theo Colborn ◽  
Tyrone B. Hayes ◽  
Jerrold J. Heindel ◽  
David R. Jacobs ◽  
...  
Keyword(s):  
Dose Response ◽  
Low Dose ◽  
Endocrine Disrupting Chemicals ◽  
Low Doses ◽  
Response Curves ◽  
Toxicological Studies ◽  
Endocrine Disrupting ◽  
Dose Effects ◽  
Dose Response Curves ◽  
Low Dose Effects

For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health.

CHANGES IN ADRENAL ZONA GLOMERULOSA CELLS OF RATS EXPOSED TO LOW DOSES OF DDT DURING POSTNATAL DEVELOPMENT

2018 ◽  
Vol 26 (2) ◽  
pp. 25-30
Author(s):  
D.A. Tsomartova ◽  
◽  
N.V. Yaglova ◽  
S.S. Obernikhin ◽  
S.V. Nazimova ◽  
...  
Keyword(s):  
Postnatal Development ◽  
Zona Glomerulosa ◽  
Low Doses ◽  
Glomerulosa Cells ◽  
Zona Glomerulosa Cells

scholarly journals Differential Disrupting Effects of Prolonged Low-Dose Exposure to Dichlorodiphenyltrichloroethane on Androgen and Estrogen Production in Males

2021 ◽  
Vol 22 (6) ◽  
pp. 3155
Author(s):  
Nataliya V. Yaglova ◽  
Dibakhan A. Tsomartova ◽  
Sergey S. Obernikhin ◽  
Valentin V. Yaglov ◽  
Svetlana V. Nazimova ◽  
...  
Keyword(s):  
Postnatal Development ◽  
Low Dose ◽  
Serum Levels ◽  
Sex Steroid ◽  
Postnatal Exposure ◽  
Hormone Production ◽  
Sex Steroid Hormone ◽  
Testosterone Production ◽  
Estrogen Production ◽  
Male Wistar Rats

Dichlorodiphenyltrichloroethane (DDT) is the most widespread, persistent pollutant and endocrine disruptor on the planet. Although DDT has been found to block androgen receptors, the effects of its low-dose exposure in different periods of ontogeny on the male reproductive system remain unclear. We evaluate sex steroid hormone production in the pubertal period and after maturation in male Wistar rats exposed to low doses of o,p’-DDT, either during prenatal and postnatal development or postnatal development alone. Prenatally and postnatally exposed rats exhibit lower testosterone production and increased estradiol and estriol serum levels after maturation, associated with the delayed growth of gonads. Postnatally exposed rats demonstrate accelerated growth of gonads and higher testosterone production in the pubertal period. In contrast to the previous group, they do not present raised estradiol production. All of the exposed animals exhibit a reduced conversion of progesterone to 17OH-progesterone after sexual maturation, which indicates putative attenuation of sex steroid production. Thus, the study reveals age-dependent outcomes of low-dose exposure to DDT. Prenatal onset of exposure results in the later onset of androgen production and the enhanced conversion of androgens to estrogens after puberty, while postnatal exposure induces the earlier onset of androgen secretion.

scholarly journals The influence of high and low doses of acrylamide on porcine erythropoiesis

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Anna Snarska ◽  
Katarzyna Palus ◽  
Dominika Wysocka ◽  
Liliana Rytel
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Light Microscope ◽  
Cytotoxic Effect ◽  
Low Dose ◽  
Low Doses ◽  
Widespread Occurrence ◽  
Cytological Evaluation ◽  
The Impact ◽  
Experimental Group

AbstractIntroductionDue to the widespread occurrence of acrylamide in the environment, its likely carcinogen status, and the suitability of the pig model as a human analogue, the authors decided to evaluate the impact of high and low doses of this compound on the processes of erythropoiesis in swine bone marrow.Material and MethodsThe experiment was carried out on Danish Landrace pigs at the age of eight weeks and body weight about 20 kg. The animals were divided into three equal groups consisting of five pigs in each. Control animals received empty gelatin capsules (placebos). Animals from the first experimental group received a low dose of acrylamide of 0.5 μg/kg b.w./day (> 99% purity; Sigma-Aldrich, Poland), and animals from the second experimental group received a dose 10 times higher. Placebos and acrylamide capsules were administered with feed every morning for 28 days. After anaesthetisation of the animals, bone marrow from the femur was collected into tubes without an anticoagulant on days 0 and 28. After drying and staining, bone marrow smears were subjected to detailed cytological evaluation using a light microscope.ResultsThis study showed that high and low doses of acrylamide affected the process of porcine erythropoiesis. The cytotoxic effect of acrylamide on this process was demonstrated in a change of the polychromatic erythroblasts/normochromatic erythroblasts ratio.ConclusionBoth doses of acrylamide caused a decrease in the number of ortho- and polychromatic erythroblasts.

scholarly journals Differences in adrenal steroid hormones production in pubertal rats exposed to low doses of endocrine disruptor DDT during prenatal and postnatal development

2017 ◽  
Vol 63 (4) ◽  
pp. 306-311 ◽  
Author(s):  
N.V. Yaglova ◽  
D.A. Tsomartova ◽  
V.V. Yaglov
Keyword(s):  
Postnatal Development ◽  
Steroid Hormones ◽  
Endocrine Disruptor ◽  
Wistar Rats ◽  
Zona Glomerulosa ◽  
Low Doses ◽  
Adrenal Steroid ◽  
Steroid Profile ◽  
Male Wistar Rats ◽  
Circulatory Disorders

Production of adrenal steroid hormones in pubertal male Wistar rats exposed to low doses of DDT during both prenatal and postnatal and only postnatal development was evaluated. Altered production of all types of steroid hormones and serum steroid profile with opposite changes in rats exposed prenatally and postnatally, and only postnatally was found. The study showed that daily exposure to low doses of DDT enhanced conversion of progesterone to 17OH-progesterone and did not exert selective antiandrogenic or proestrogenic action unlike effect of toxic and subtoxic doses. Impaired morphogenesis of the adrenal cortex and circulatory disorders in zona glomerulosa contributed to reduced aldosterone and sex steroid hormones production.

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