Enhanced thymocyte apoptosis induced by maternal undernutrition in late gestation results in declined mature T cells in rat fetal thymus

Qu, Wen; Ma, Liang; Yan, Hui-yi; Liu, Sha; Liu, Hanxiao; Chen, Ting; Hou, Lifang; Ping, Jie

doi:10.1016/j.etap.2017.08.018

Cited by 3 publications

(3 citation statements)

References 29 publications

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“…Functional tests on circulating lymphocytes or immune challenge by injection of microbes or toxins would have helped to reveal the relevance of the thymic changes observed. Apoptotic mechanisms seem particularly enhanced in thymic cell maturation process in the context of malnutrition (14,15,38) . Yet, the present study was not designed to explore the related underlying mechanisms, especially enhanced apoptotic features in early cortical stages of thymocyte maturation (14,15) .…”

Section: Limits and Perspectivesmentioning

confidence: 99%

“…Apoptotic mechanisms seem particularly enhanced in thymic cell maturation process in the context of malnutrition (14,15,38) . Yet, the present study was not designed to explore the related underlying mechanisms, especially enhanced apoptotic features in early cortical stages of thymocyte maturation (14,15) . Although the developing thymus is particularly sensitive to malnutrition, little is known about the underlying mechanisms altering the cell selection process in a thymus exposed to early malnutrition (3,44) .…”

Section: Limits and Perspectivesmentioning

confidence: 99%

“…Consequently, immune function can be permanently impaired later in life (9,10) . Animal studies have demonstrated that malnutrition during development induces an involution of the thymus due to massive cell apoptosis in the thymic cortex during the early stages of thymopoiesis (11)(12)(13)(14)(15) . The lymphotoxin β receptor controls early thymic colonisation by blood-borne thymocyte progenitors from bone marrow and allows terminal differentiation of medullary thymic epithelial cells involved in the acquisition of self-tolerance (16,17) .…”

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confidence: 99%

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Intra-uterine growth restriction induced by maternal low-protein diet causes long-term alterations of thymic structure and function in adult male rat offspring

et al. 2020

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Early malnutrition, the first environmental cause of intra-uterine growth restriction, impairs development of the thymus. Alterations of the thymic structure and function are reported at young ages in murine and ovine models. However, descriptions of thymic consequences of fetal malnutrition at adulthood are scarce. The present study investigates thymic structure, protein expression and cell selection process observed at postnatal day 180 (PND180) in male offspring of rats exposed to maternal low-protein diet (mLPD) compared with control diet during gestation. The thymic index was lower in adult offspring exposed to mLPD (P < 0·05). The thymic cortico-medullar ratio was lower in adult offspring exposed to mLPD (P < 0·05). At PND180, the protein expression of the lymphotoxin β receptor (P < 0·05), the autoimmune regulator (P < 0·05) and Forkhead Box P3 (FoxP3; P < 0·05) was all significantly lower in the mLPD group. The CD4+:CD8+ single-positive thymocyte subpopulation ratio and CD4+:CD8+ lymphocyte subpopulation ratio were increased in the mLPD group (P < 0·05). Among CD3+ lymphocytes, the proportions of CD4+CD8+ double-positive lymphocytes, CD31+ recent thymic emigrants and CD4+FoxP3+ lymphocytes were not significantly different between mLPD and control groups. These findings suggest mLPD during gestation induced long-lasting alterations in the development of thymic structure and thymic cell maturation and selection process in adult male rat offspring.

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Section: Limits and Perspectivesmentioning

confidence: 99%

Section: Limits and Perspectivesmentioning

confidence: 99%

mentioning

confidence: 99%

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Intra-uterine growth restriction induced by maternal low-protein diet causes long-term alterations of thymic structure and function in adult male rat offspring

et al. 2020

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Prenatal nicotine exposure induces thymic hypoplasia in mice offspring from neonatal to adulthood

Zhao

Wen

et al. 2019

Toxicology Letters

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Impact of Gestational Diabetes on the Thymus Gland of Rat’s Offspring and the Possible Ameliorating Effect of Thymoquinone: Biochemical, Histological, and Immunohistochemical Study

Mokhtar

Mokhemer

Mohammed

et al. 2023

Microscopy and Microanalysis

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Gestational diabetes mellitus (GDM) not only has short-term side effects on offspring but also has an increased risk of developing chronic diseases in adulthood. The thymus gland is a vital organ of immune system and thymoquinone (TQ) has an immunomodulatory effect. This study aimed to investigate the long-term adverse effects of GDM on offspring’s thymus gland and the ameliorating effect of TQ. Pregnant rats were divided into four groups: C-group, T-group, GD-group, and GD + T-group. Offspring of all groups were subdivided into two subgroups, one sacrificed on day 21 and the other on day 42. The thymus of the offspring in the GD-group at both time points revealed a significant decrease in thymic weight, superoxide dismutase (SOD), and reduced glutathione (GSH) levels with a significant increase in malondialdehyde (MDA), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α) levels. Moreover, there were microscopic degenerative changes, a significant decrease in C/M ratio, CD3, CD4, and CD8 immune expression, and a significant increase in activated caspase-3 immune expression. Interestingly, TQ administration revealed a significant increase in thymic weight, thymic SOD and GSH, C/M ratio, and CD3, CD4, and CD8 immune expression with a significant decrease in MDA, IL-8, TNF-α and activated caspase-3. For the first time, this study has shown that GDM causes long-term oxidative stress, apoptosis, and inflammation in offspring’s thymus and these changes could be attenuated by TQ.

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Enhanced thymocyte apoptosis induced by maternal undernutrition in late gestation results in declined mature T cells in rat fetal thymus

Cited by 3 publications

References 29 publications

Intra-uterine growth restriction induced by maternal low-protein diet causes long-term alterations of thymic structure and function in adult male rat offspring

Intra-uterine growth restriction induced by maternal low-protein diet causes long-term alterations of thymic structure and function in adult male rat offspring

Prenatal nicotine exposure induces thymic hypoplasia in mice offspring from neonatal to adulthood

Impact of Gestational Diabetes on the Thymus Gland of Rat’s Offspring and the Possible Ameliorating Effect of Thymoquinone: Biochemical, Histological, and Immunohistochemical Study

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