Fetal thymus size in pregnant women with diabetic diseases

Dörnemann, R; Koch, Raphael; Möllmann, Ute; Falkenberg, Maria; Möllers, Mareike; Klockenbusch, Walter; Schmitz, Ralf

doi:10.1515/jpm-2016-0400

Cited by 30 publications

(35 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, the finding of an association between fetal thymus size and ma- ternal diseases like preeclampsia (associated with a decreased thymus size; [8]) or rheumatic diseases (associated with an increased thymus size; [4]) does not apply for pregnancies complicated by T1D. This result seems contrary to two recent studies reporting a decreased fetal thymus size in pregnancies affected by maternal diabetes [4,15]. However, in both studies the ultrasound investigations were performed earlier (1st trimester or at a median gestational age of 21.0 weeks, respectively) and pregnancies were complicated by diabetes in general and not particularly by autoimmune T1D.…”

Section: Discussionmentioning

confidence: 90%

“…However, in both studies the ultrasound investigations were performed earlier (1st trimester or at a median gestational age of 21.0 weeks, respectively) and pregnancies were complicated by diabetes in general and not particularly by autoimmune T1D. In one of the two studies [15], the authors reported a decreased thymus size in diabetic pregnancies complicated by gestational diabetes (n = 98) or preexisting diabetes of any type (n = 63), and suggested that metabolic disturbanc-es such as maternal hyperglycemia could be a fetal stress factor, resulting in a smaller thymus size. In contrast, we analyzed the thymus size of pregnancies with autoimmune T1D only, and excluded any other preexisting diabetes form, in particular type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Thymus Growth and Fetal Immune Responses in Diabetic Pregnancies

et al. 2017

View full text Add to dashboard Cite

Type 1 diabetes (T1D) during pregnancy possibly affects the development of the thymus and the maturation of the immune system in the offspring. The aim of the ImmunDiabRisk study was to investigate thymus growth and maternal and fetal immune responses in pregnancies with and without T1D. The thymus circumferences of the fetuses of pregnant women with T1D (n=49) and without diabetes (n=59) were measured using ultrasound around the 29th gestational week and standardized for gestational age. Simultaneously, the frequencies and total numbers of cell markers were analyzed by flow cytometry in maternal peripheral blood, and at birth in umbilical cord blood. The standardized circumference of the thymus was similar in fetuses of mothers with and without T1D (p=0.26). We observed higher numbers of FOXP3 Tregs, memory Tregs, erythrocytes, and lymphocytes in the cord blood from T1D pregnancies (p=0.01, p=0.002, p=0.002 and p=0.02, respectively). The frequencies of CD4+/CD8+ T cells correlated positively in maternal blood and umbilical cord blood of mother-child pairs, as did the levels of neutrophils (Spearman's correlation coefficient r=0.43, p=0.02 for CD4+/CD8+ cells; r=0.46, p=0.03 for neutrophils), while no significant correlations were observed between thymus circumference and any cell markers in the child. Parts of the prenatal immune system seem to develop differently in the offspring of mothers with and without T1D. The correlation of Tregs between maternal blood and cord blood may indicate a significant cross-talk between the maternal and fetal immune system.

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Thymus Growth and Fetal Immune Responses in Diabetic Pregnancies

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Gestational diabetes is a distinct teratogen affecting pregnancy, with newborns having congenital features overlapping with 22q11.2del (Kucera, 1971;Mills, 2010;Sacks et al, 2012;Dornemann et al, 2017). In fact, about 18% of infants with a thymic aplasia who did not have deletions on chromosome 22q11.2 and required a thymic tissue transplant were born to mothers with a clinical history of gestational diabetes (Markert et al, 2007).…”

Section: The Genetic and Epigenetic Regulation Coupled To Tbx1 Functionsmentioning

confidence: 99%

The Genetics and Epigenetics of 22q11.2 Deletion Syndrome

Morena

Oers

2020

Front. Genet.

View full text Add to dashboard Cite

Chromosome 22q11.2 deletion syndrome (22q11.2del) is a complex, multi-organ disorder noted for its varying severity and penetrance among those affected. The clinical problems comprise congenital malformations; cardiac problems including outflow tract defects, hypoplasia of the thymus, hypoparathyroidism, and/or dysmorphic facial features. Additional clinical issues that can appear over time are autoimmunity, renal insufficiency, developmental delay, malignancy and neurological manifestations such as schizophrenia. The majority of individuals with 22q11.2del have a 3 Mb deletion of DNA on chromosome 22, leading to a haploinsufficiency of~106 genes, which comprise coding RNAs, noncoding RNAs, and pseudogenes. The consequent haploinsufficiency of many of the coding genes are well described, including the key roles of T-box Transcription Factor 1 (TBX1) and DiGeorge Critical Region 8 (DGCR8) in the clinical phenotypes. However, the haploinsufficiency of these genes alone cannot account for the tremendous variation in the severity and penetrance of the clinical complications among those affected. Recent RNA and DNA sequencing approaches are uncovering novel genetic and epigenetic differences among 22q11.2del patients that can influence disease severity. In this review, the role of coding and noncoding genes, including microRNAs (miRNA) and long noncoding RNAs (lncRNAs), will be discussed in relation to their bearing on 22q11.2del with an emphasis on TBX1.

show abstract

“…Maternal diabetes and systemic use of retinoic acid (RA) derivatives during pregnancy can cause long-term thymic hypoplasia in newborns (18)(19)(20)(21). What's more, gestational diabetes leads to congenital malformations in the developing fetus which overlap with those noted in individuals with 22q11.2del; hypoplasia/aplasia of the thymus, cardiac outflow tract defects, and hypoparathyroidism (160)(161)(162)(163). Estimates suggest that 18% of infants who required a thymic tissue transplant due to an aplasia of this tissue, and did not have 22q11.2del, were born to mothers who had maternal diabetes (72).…”

Section: Clinical Conditions During Pregnancy Leading To a Thymic Hypoplasia/aplasiamentioning

confidence: 99%

Molecular Insights Into the Causes of Human Thymic Hypoplasia With Animal Models

2020

View full text Add to dashboard Cite

22q11.2 deletion syndrome (DiGeorge), CHARGE syndrome, Nude/SCID and otofaciocervical syndrome type 2 (OTFCS2) are distinct clinical conditions in humans that can result in hypoplasia and occasionally, aplasia of the thymus. Thymic hypoplasia/aplasia is first suggested by absence or significantly reduced numbers of recent thymic emigrants, revealed in standard-of-care newborn screens for T cell receptor excision circles (TRECs). Subsequent clinical assessments will often indicate whether genetic mutations are causal to the low T cell output from the thymus. However, the molecular mechanisms leading to the thymic hypoplasia/aplasia in diverse human syndromes are not fully understood, partly because the problems of the thymus originate during embryogenesis. Rodent and Zebrafish models of these clinical syndromes have been used to better define the underlying basis of the clinical presentations. Results from these animal models are uncovering contributions of different cell types in the specification, differentiation, and expansion of the thymus. Cell populations such as epithelial cells, mesenchymal cells, endothelial cells, and thymocytes are variably affected depending on the human syndrome responsible for the thymic hypoplasia. In the current review, findings from the diverse animal models will be described in relation to the clinical phenotypes. Importantly, these results are suggesting new strategies for regenerating thymic tissue in patients with distinct congenital disorders.

show abstract

Fetal thymus size in pregnant women with diabetic diseases

Abstract: Reduced fetal thymus size seems to be associated with diabetic pregnancy. We introduce fetal thymus size as a new potential prognostic parameter for maternal diabetes.

Cited by 30 publications

References 22 publications

Thymus Growth and Fetal Immune Responses in Diabetic Pregnancies

Thymus Growth and Fetal Immune Responses in Diabetic Pregnancies

The Genetics and Epigenetics of 22q11.2 Deletion Syndrome

Molecular Insights Into the Causes of Human Thymic Hypoplasia With Animal Models

Contact Info

Product

Resources

About