Fetal Thymus Research Articles

Origin, phenotype and autoimmune potential of T cells in human immune system mice receiving neonatal human thymus tissue.

Robust human immune system (HIS) mice are created using human fetal thymus tissue and hematopoietic stem cells (HSCs). A HIS mouse model using neonatal human thymus tissue and umbilical cord blood (CB) HSCs (NeoHu) was recently described. We improved the model by removing the native murine thymus, which can also generate human T cells, and demonstrated definitively the capacity of human T cells to develop in a grafted neonatal human thymus. Human T cells derived from the neonatal thymus tissue appeared in peripheral blood early post-transplantation and CB-derived T cells appeared later. Naïve T cells were demonstrated in peripheral blood but effector memory and T peripheral helper phenotypes predominated later, in association with development of autoimmunity in some animals. Treatment of thymus grafts with 2-deoxyglucose (2-DG) increased the proportion of stem cells derived from injected HSCs, delayed onset of autoimmune disease, reduced early T cell reconstitution, and reduced effector/memory T cell conversion. Younger neonatal human thymus tissue was associated with improved T cell reconstitution. While the NeoHu model bypasses the need for fetal tissue, it has yet to demonstrate equivalent reconstitution to fetal tissue, though 2-DG can improve results by removing native thymocytes prior to transplantation.

Fetal Tissues Reflect Decidual-Placental Inflammation

Abstract Maternal inflammation can negatively impact the development of the fetus, leading to long term adverse health outcomes. We previously reported that injection of Tisseel (surgical glue) into the maternal-fetal interface led to necrosis and inflammation skewing the peripheral fetal immunome into a pro-inflammatory state. Here, we extend those observations and report that decidual inflammation leads to similar outcomes in fetal organs. Tisseel or saline (n = 3) was injected directly into the placenta of pregnant (~GD90) rhesus macaques. C-sections were performed at ~GD150. Fetal tissues (lung, thymus, spleen, liver) were collected at necropsy, homogenates were prepared from all fetal tissues, and cytokine levels were measured by cytometric bead analysis. Mononuclear cell suspensions were prepared from thymus and spleen, labeled with antibodies against major immune cell lineages, and acquired using the Cytek Aurora. Data was analyzed using Specter (R), statistical significance was determined by Student’s t-test (p < 0.05). Tisseel group fetuses had higher levels of IL17A (lung, spleen), MCP1, and IL6 (liver). Interestingly, there was a trend towards elevated IL6 in the thymus of saline group fetuses. Additionally RORγt+ T cells were elevated in the thymus of Tisseel group fetuses, while T Regswere elevated in saline group. The spleen from Tisseel group fetuses had a higher proportion of T H1-like cells. Interestingly, T-bet+ B cells, linked to autoimmune disorders, were also elevated in the Tisseel group. Our preliminary results suggest that decidual/placental inflammation leads to a pro-inflammatory immunome in fetal organs. Further studies are needed to determine the functional properties of these altered immune populations.

Sequential and interwoven requirements for HEB and Id3 in fetal gamma-delta T cell commitment and functional programming

Abstract Two major developmental steps are necessary for the generation of innate IL-17 producing γδ T cells. First, T cell precursors in the fetal thymus commit to either the αβ or the γδ T cell lineage. This is followed by a second stage of differentiation into subsets that can produce either IL-17 (γδT17) or IFNγ (γδT1) cells. Both developmental events are dependent on TCR signal strength, but how this is interpreted at the molecular level has been unclear. Id3, which antagonizes the activity of HEB transcription factors, is upregulated in proportion to TCR signal strength, providing an important link between TCR signaling and gene expression. We previously found that γδ T cells in mice lacking HEB were impaired in IL-17 production. To better understand the molecular basis of this defect, we conducted single cell RNA-sequencing on fetal thymic γδ T cells. In WT cells, the ratio of HEB to Id3 was highest in populations undergoing γδ T cell commitment, whereas later populations were dominated by Id3. Comparing scRNA-seq datasets from WT and HEB-deficient γδ T cells revealed a profound shift in TCRγ and TCRδ chain expression. This was accompanied by a decrease in key regulators of early γδ T cell development. Id3 expression was also severely decreased. Accordingly, Id3-deficient mice were impaired in their ability to generate γδT17 cells. However, γδ T cells from Id3-deficient mice showed a decrease in second stage γδT17 regulators, rather than the first stage regulators defective in HEB-deficient mice. Therefore, distinct ratios of HEB and Id3 are required during the γδ T cell commitment, and HEB is instrumental in inducing Id3 to enable functional programming of γδT17 cells in the fetal thymus. Supported by grants from CIHR (201610PJT), NSERC (RGPIN-2020-05596) and NIH (1P01AI102853-06)

Dendritic epidermal T cells (DETC) are not required for control of skin Staph infections

Abstract Staphylococcal bacteria are a common cause of skin infections in mice and humans. γδ T cells and the cytokine IL-17 are important in controlling these infections. To test roles for IL-17 in autoimmune Ets1 knockout (KO) mice, we generated double knockout (DKO) mice lacking both Ets1 and IL-17RA. We found that DKO mice develop worse autoimmune disease than Ets1 KO mice and are also susceptible to spontaneous Staphylococcus xylosus skin infections. While IL-17RA KO mice also develop skin lesions, these lesions are found at a higher rate and increased severity in DKO mice. Furthermore, exogenous infection of DKO skin with bioluminescent Staphylococcus aureus results in a failure to clear the bacteria, while IL-17RA KO mice are able to clear. Given that γδ T cells are important in controlling Staph skin infections, we examined these populations and found that both Ets1 KO and DKO mice lack the dendritic epidermal T cells (DETC), while other γδ T cell subsets are present. Further analysis showed that DETC progenitors are present in the fetal thymus of Ets1 KO mice, but DETC are missing from the skin of P5 and adult mice lacking Ets1. We hypothesized that loss of DETC (due to absence of Ets1) might cooperate with loss of IL-17 signaling (due to loss of IL-17RA) to create susceptibility to skin infections. To determine if DETC have a specific contribution to the skin immune response to Staphylococcal bacteria, we depleted DETC from wild-type mice using antibody against TCR Vγ5 followed by S. aureus infection. We found that DETC are not required to clear skin Staph infections, since depleted mice cleared with the same kinetics as non-depleted mice. Studies are in progress to further examine the roles of other γδ T cell populations in clearance of skin Staph infections. Supported by grant from NIH (R01 AI122720)

Assessment of fetal thymus size and BMI in pregnant women with diabetes.

The purpose of this study is to demonstrate whether diabetes during pregnancy affects the development of the fetal immune system. The background: evaluation of potential complications in diabetic pregnancy. The objective is evaluation of the significance of a new ultrasound method of thymus size in pregnancies complicated by diabetes. The analysis was performed with the use of IBM SPSS Statistics 25.0 software. The Mann-Whitney U test was used for comparison of two groups, i.e., diabetic pregnancies and non-diabetic pregnancies, whereas Kruskal-Wallis H test was used to compare multiple groups. A linear regression model was used to determine the correlation between the type of diabetes and fetal thymus size as well as between maternal body mass index (BMI) and fetal thymus size. The significance level α was set at 0.05. A comparison between diabetic and non-diabetic pregnancies was made with the use of Kruskal-Wallis H test. The compared groups included women without gestational diabetes, with pre-gestational diabetes, gestational diabetes managed by diet and gestational diabetes treated with insulin and diet. The analysis revealed significant differences between the compared groups, H (3) = 23.06; p < 0.001; ƞ2 = 0.04. The additional post hoc Dunn's test with Bonferroni correction of the significance level was used to explore specific differences between group means. The results of this detailed analysis indicated that foetuses of diabetic mothers treated with diet had smaller thymus than foetuses of non-diabetic mothers (p = 0.001). Linear regression analysis was used to establish whether maternal BMI (defined as the body mass divided by the square of the body height and expressed in units of kg/m²) affects fetal thymus size. The analysis found no correlation between maternal BMI divided into the following categories: 18.5-24.99 normal weight, 25-29.99 overweight, 30.00-34.99 obese class I, 35.00-39.99 obese class II and ≥ 40.00 very severely obese, and fetal thymus size, b = -1.82; SE = 2.17; t = -0.84; p = 0.405; R2 < 0.01. Thymus size is statistically smaller in foetuses of diabetic mothers when compared to healthy controls. Overweighted and obese pregnancy is not a factor affecting fetal thymus size.

Evaluation of fetal thymus size in maternal autoimmune diseases: systemic lupus erythematosus, Sjögren's syndrome and antiphospholipid antibody syndrome.

To investigate the effect of inflammation on the fetal thymus-thoracic ratio (TTR) in pregnant women with systemic lupus erythematosus (SLE), Sjögren's syndrome (SS) and antiphospholipid antibody syndrome (APS). This prospective case-control study included 45 pregnant women with SLE, SS, and APS and 90 gestational age-matched healthy pregnant women between 24 and 37 gestational weeks. The ratio of the anteroposterior fetal thymus length to the transverse mediastinal length was calculated as the TTR in the study groups. Fetal TTR was significantly lower in the case group (p < 0.001). Fetal TTR in the APS group was significantly lower than SS group (p = 006). The patients using hydroxychloroquine (HCQ) had significantly higher fetal TTR compared to patients not using HCQ (p = 0.004). A moderate negative correlation was found between the disease duration and fetal TTR (r = - 0.552, p < 0.001). In predicting admission to the neonatal intensive unit care (NICU), a value of 0.31 was found for the fetal TTR with a sensitivity of 83.3% and a specificity of 69% CONCLUSION: Maternal inflammation in pregnancies with autoimmune diseases may affect the intrauterine milieu of the fetus and cause a lower fetal TTR. Additionally, the lower level of fetal TTR may be more effective and beneficial for the clinician if combined with other risk factors in predicting NICU admission.

Natural γδT17 cell development and functional acquisition is governed by the mTORC2-c-Maf-controlled mitochondrial fission pathway

Natural IL-17-producing γδ Tcells (γδT17 cells) are unconventional innate-like Tcells that undergo functional programming in the fetal thymus. However, the intrinsic metabolic mechanisms of γδT17 cell development remain undefined. Here, we demonstrate that mTORC2, not mTORC1, selectively controls the functional fate commitment of γδT17 cells through regulating transcription factor c-Maf expression. scRNA-seq data suggest that fetal and adult γδT17 cells predominately utilize mitochondrial metabolism. mTORC2 deficiency results in impaired Drp1-mediated mitochondrial fission and mitochondrial dysfunction characterized by mitochondrial membrane potential (ΔΨm) loss, reduced oxidative phosphorylation (OXPHOS), and subsequent ATP depletion. Treatment with the Drp1 inhibitor Mdivi-1 alleviates imiquimod-induced skin inflammation. Reconstitution of intracellular ATP levels by ATP-encapsulated liposome completely rescues γδT17 defect caused by mTORC2 deficiency, revealing the fundamental role of metabolite ATP in γδT17 development. These results provide an in-depth insight into the intrinsic link between the mitochondrial OXPHOS pathway and γδT17 thymic programming and functional acquisition.

Can diabetes influence fetal thymus size during pregnancy?

The aim of the study was to evaluate fetal thymus size by sonography in diabetic pregnancies and its relationship with diabetes type. In this prospectively designed case-control study, fetal thymus transverse diameter and circumference of the fetal thymus were measured. Also, TTR (thymic-thoracic ratio) was assessed in 288 healthy and 105 diabetic pregnancies. Patients were divided into subgroups as diet-controlled gestational diabetes (GDMA1, n = 40), insulin-dependent (GDMA2, n = 42), and pregestational diabetes mellitus (PGDM, n = 23). GDM was diagnosed between 24 and 28 weeks of gestation with a 75 g oral glucose tolerance test. Measurements were compared to the healthy control group. Pairwise comparisons with Bonferroni correction determined which type of diabetes was independently associated with a small fetal thymus. All 3 maternal diabetes categories had smaller fetal thymus size than controls (p < 0.05). TTR were lowest in PGDM (p < 0.05). Gestational diabetes is associated with smaller fetal thymus size. Pregestational diabetes may be associated with a smaller fetal thymus compared to diet-controlled GDM. Also, the thymus size may be even smaller in those with poor blood glucose regulation.

Fetal büyüme kısıtlılığı ile komplike gebeliklerde fetal timus boyutunun değerlendirilmesi

Aim: To evaluate fetal thymus size using the thymic-thoracic ratio (TTR) in women with a pregnancy complicated with fetal growth restriction (FGR) and to assess the relationship with adverse perinatal outcomes. &#x0D; Materials and Method: A total of 35 pregnant women with FGR and 42 healthy pregnant women with similar demographic characteristics were included in this prospective study. In the FGR group, cases with pathological doppler flow parameters of absent end-diastolic flow (AEDF) in an umbilical artery and cerebroplacental ratio (CPR)

Finding the best method for screening for gestational diabetes mellitus: fetal thymic-thoracic ratio or fetal thymus transverse diameter.

The aim of this study was to compare the efficiency of fetal thymic-thoracic ratio and fetal thymus transverse diameter measurements in gestational diabetes mellitus. Fetal thymic-thoracic ratio and fetal thymus transverse diameter were assessed in 360 pregnant women. Patients were examined in two groups: 180 gestational diabetes mellitus (study group) and 180 healthy pregnant women (control group). There were no statistically significant differences between the cases with gestational diabetes mellitus and the control group in terms of fetal thymus transverse diameter; however, the fetal thymic-thoracic ratio was found to be significantly lower in cases with gestational diabetes mellitus compared to that in the control group (p<0.001). The fetal thymic-thoracic ratio is superior to the fetal thymus transverse diameter in evaluating the fetal thymus size.

Speed and navigation control of thymocyte development by the fetal T-cell gene regulatory network.

T-cell differentiation is a tightly regulated developmental program governed by interactions between transcription factors (TFs) and chromatin landscapes and affected by signals received from the thymic stroma. This process is marked by a series of checkpoints: T-lineage commitment, T-cell receptor (TCR)β selection, and positive and negative selection. Dynamically changing combinations of TFs drive differentiation along the T-lineage trajectory, through mechanisms that have been most extensively dissected in adult mouse T-lineage cells. However, fetal T-cell development differs from adult in ways that suggest that these TF mechanisms are not fully deterministic. The first wave of fetal T-cell differentiation occurs during a unique developmental window during thymic morphogenesis, shows more rapid kinetics of differentiation with fewer rounds of cell division, and gives rise to unique populations of innate lymphoid cells (ILCs) and invariant γδT cells that are not generated in the adult thymus. As the characteristic kinetics and progeny biases are cell-intrinsic properties of thymic progenitors, the differences could be based on distinct TF network circuitry within the progenitors themselves. Here, we review recent single-cell transcriptome data that illuminate the TF networks involved in T-cell differentiation in the fetal and adult mouse thymus.

Fetal thymic-thoracic ratio in pregnancies with familial Mediterranean fever

ObjectiveTo investigate the thymic-thoracic ratio (TTR) in fetuses of pregnant women with familial Mediterranean fever (FMF). Study designThis prospective case-control study was conducted with 43 pregnant women diagnosed with FMF and 43 gestational age-matched healthy controls. Pregnant women between 28 and 40 weeks who applied for antenatal care were included in the study. Healthy pregnant women whose age and gestational week matched were defined as the control group. ResultsTTR was significantly lower in the FMF group compared to the control group. The mean TTR value was 0.34 ± 0.03 in the FMF group and 0.36 ± 0.02 in the control group (p < 0.001). TTR was significantly lower in those with FMF duration of ten years or more than those with FMF of less than ten years (p < 0.001). In addition, pregnant women who had an attack during pregnancy had lower TTR (p < 0.001). TTR was significantly associated with white blood cell count, neutrophil count, monocyte count, platelet count, mean platelet volume, C-reactive protein, red cell distribution width, and platelet‑to‑lymphocyte ratio. ConclusionBesides the inflammation during the FMF attacks, the ongoing subclinical inflammation between the attacks might affect the fetal thymus size. Since TTR is an easily applicable method, it can be used to evaluate fetal inflammation.

Decreased fetal thymus size in pregnancies after assisted reproductive technologies

Objective To compare the size of the fetal thymus, using both fetal thymic-thoracic ratio and fetal thymus transverse diameter values in Assisted reproductive technologies (ART) or naturally conceived pregnancies. Methods In this retrospective study, fetal thymic-thoracic ratio and fetal thymus transverse diameter were evaluated in 204 pregnant women. Patients were examined in two groups. The study included 58 Intracytoplasmic sperm injection (ICSI) patients (study group) and 146 healthy pregnant women (control group). Results Fetal thymic-thoracic ratio in ART pregnancies were found to be statistically significantly lower than that of the control group (p = .001). Also, the fetal thymus transverse diameter value was found to be statistically significantly lower in ART pregnancies compared to that of the control group (p = .001). Conclusions The size of the fetal thymus, manifested with a decrease in both fetal thymic-thoracic ratio and thymus transverse diameter values, decreased in ART pregnancies.

Surfing on the waves of the human γδ T cell ontogenic sea.

While γδ T cells are present virtually in all vertebrates, there is a remarkable lack of conservation of the TRG and TRD loci underlying the generation of the γδ T cell receptor (TCR), which is associated with the generation of species-specific γδ T cells. A prominent example is the human phosphoantigen-reactive Vγ9Vδ2 T cell subset that is absent in mice. Murine γδ thymocyte cells were among the first immune cells identified to follow a wave-based layered development during embryonic and early life, and since this initial observation, in-depth insight has been obtained in their thymic ontogeny. By contrast, less is known about the development of human γδ T cells, especially regarding the generation of γδ thymocyte waves. Here, after providing an overview of thymic γδ wave generation in several vertebrate classes, we review the evidence for γδ waves in the human fetal thymus, where single-cell technologies have allowed the breakdown of human γδ thymocytes into functional waves with important TCR associations. Finally, we discuss the possible mechanisms contributing to the generation of waves of γδ thymocytes and their possible significance in the periphery.

Two- and Three-Dimensional Ultrasonographic Evaluation of the Fetal Thymus in Women with Preterm PrematureRupture of Membranes: A Prospective Study

Objective: To evaluate the relationship between fetal thymus diameter and perinatal outcomes in preterm premature rupture of membranes (PPROM) cases and to compare three-dimensional (3D) fetal thymus volume in the same cases. Material and Methods: This was a prospective study from March 2019 through March 2020. Women diagnosed with PPROM between 24 and 33+6 weeks of gestation were included. Pregnancies were divided into 2 groups as small and normal according to the thymus size nomogram. The virtual organ computeraided analysis software calculated the volumes automatically. Results: In 41 patients, measurements could be successfully acquired with twodimensional and 3D sonography. Twenty eight (68.3%) patients were in the small thymus group and 13 patients (31.7%) were in the normal thymus group. The probability of clinical chorioamnionitis increased 7.7-fold-times in cases with small thymus (odds ratio 7.7, 95% confidence interval 1.1-67.4, p=0.038). The latency period was significantly higher in the normal thymus group. The correlation between transverse diameter and thymus volume was analyzed according to gestational age at ultrasound measurement and a significant correlation was observed between them. Conclusion: A small transverse diameter of the thymus in PPROM cases may be associated with clinical chorioamnionitis, and a normal thymus diameter may predict a longer latency period. In addition, although transverse thymus diameter was correlated with thymus volume, no significant volume difference was observed between the groups when percentile classification was made.

An enlarged fetal thymus may be the initial response to intrauterine inflammation in pregnant women at risk for preterm birth

Fetal thymus involvement in prematurity has been studied, and this study aimed to evaluate its relationship with short cervix and amniotic fluid sludge in the second trimester of pregnancy. In this prospective cross-sectional study, 79 pregnant women (19+0 to 24+6 weeks) were included, and cervical length and the presence or absence of amniotic fluid sludge were evaluated. In the three-vessel view of the fetal thorax, the thymus was identified, and its perimeter and transverse diameter were measured and transformed to a zeta score based on gestational age. Data from 22 women with short cervix (<25 mm) and 57 patients with normal cervix (≥25 mm) were analyzed. The transverse diameter of the fetal thymus was significantly greater in the short cervix group compared to that of the normal cervix group (z-score 2.708 vs. -0.043, p=0.003). There were no significant differences in the perimeter (z-score -0.039 vs. -0.071, p=0.890) or the transverse diameter (z-score 1.297 vs. -0.004, p=0.091) of the fetal thymus associated with the presence (n=21) or absence of sludge (n=58). A short cervix is associated with an increased transverse diameter of the fetal thymus during the second trimester of gestation.

Diagnostic value of ultrasonographic assessment of fetal thymus gland size in pregnancies associated with the preterm prelabor rupture of membranes

Background: Preterm prelabor rupture of membranes (PPROM) is responsible for approximately one third of preterm deliveries. Prenatal sonographic (US) assessment of the fetal thymus has become available. This research was done to investigate the role of ultrasonographic assessment of fetal thymus size in pregnancy associated with preterm premature rupture of membrane and its relationship with fetal outcome.Methods: This prospective controlled observational study was carried out on 60 cases with maternal age from 18 to 40 years old, gestational age between 24 and 36 weeks, singleton pregnancy and associated with PROM. Cases were subdivided into two groups Group A: 30 cases with PROM, Group B: 30 normal at the same gestational age. All cases were subjected to history taking, obstetric history, maternal medical history, investigation studies and ultrasound study. Results: The amniotic fluid index had a significant decrease in group A compared with B, and the gestational diabetes mellitus had a significant increase in group A compared with B. The small fetal thymus size had a significant increase in group A compared with B (p =0.013). The Puerperal endomyometritis had a significant increase in group A (30%) compared with B (0%). The Apgar score at 5 mins (p<0.001) and Apgar score (p= 0.042) at 10 mins were significantly decreased in group A compared with B.Conclusions: In pregnancy associated with preterm premature rupture of membranes, small fetal thymus might be associated with histologic chorioamnionitis, higher rate of perinatal mortality and short‐ and long‐term neonatal morbidity however many cases remained clinically silent.

Fetal thymus in growth-restricted fetuses due to placental insufficiency

The aim of this study was to assess fetal thymus size by ultrasound in growth-restricted fetuses due to placental insufficiency and compare to high-risk and low-risk pregnancy fetuses with normal placental function. This is a nested case-control study of pregnant women followed up at a university hospital (July 2012 to July 2013). In all, 30 pregnant women presenting small fetuses for gestational age (estimated fetal weight <p10) due to placental insufficiency (umbilical artery Doppler >p95) were compared to 30 high-risk and 30 low-risk pregnancies presenting normal Doppler indices. The thymus transverse diameter and perimeter were converted into zeta score according to the normal values for gestational age. Head circumference and femur length were used to calculate ratios. Fetal thymus were significantly lower in pregnancies with placental insufficiency when compared to high-risk and low-risk pregnancies presenting, respectively, transverse diameter zeta score (-0.69±0.83 vs. 0.49±1.13 vs. 0.83±0.85, p<0.001) and P zeta score (-0.73±0.68 vs. 0.45±0.96 vs. 0.26±0.89, p<0.001). There was also a significant difference (p<0.05) in the ratios among the groups: pregnancies with placental insufficiency (TD/HC=0.10, P/FL=1.32, and P/HC=0.26), high-risk pregnancies (TD/HC=0.11, P/FL=1.40, and P/HC=0.30), and control group (DT/HC=0.11, P/FL=1.45, and P/HC=0.31). Fetal thymus size is reduced in growth-restricted fetuses due to placental insufficiency, suggesting fetal response as a consequence of the adverse environment.

Prenatal Sonographic Three-dimensional Virtual Organ Computer-assisted Analysis Thymic Volume Calculation May Predict Intrauterine Growth Restriction.

Intrauterine growth restriction (IUGR) refers to fetuses that are small for their gestational age. There is no effective test to predict this disease. The aim of our study is whether fetal three-dimensional (3D) ultrasonography (USG)-assisted thymus volume (TV) measurement predicts IUGR cases. Fetal 3D USG thymus measurement between 15 and 24 weeks of gestation was performed in a total of 100 women of reproductive age. Fetal TV was measured using the virtual organ computer-assisted analysis system program. All cases were followed up in terms of pregnancy complications until delivery. IUGR was developed in six cases in total. In cases with IUGR, mean fetal TV was found to be statistically significantly lower than in healthy cases without it. When the fetal TV was taken as 0.1645, the sensitivity was calculated as 89.5% and the specificity as 50% for predicting IUGR. The use of low fetal volume parameters is a significant and good indicator for predicting IUGR according to the binary logistic regression analysis result. According to the results of this study, 3D fetal TV measurement may be used in routine second-trimester sonographic anomaly screening to predict the development of fetal IUGR. In this way, fetal mortality and morbidity caused by IUGR may be reduced.

Morphology and Histogenesis of Thymus as a Tool for Estimating Foetal Age: A Cross-sectional Study

Introduction: The thymus is located in the superior mediastinum and anterior part of the inferior mediastinum. It plays a crucial role in the development, differentiation, and clonal expansion of T lymphocytes. In forensic cases involving foetal death, accurate estimation of foetal age is essential. When the foetus is extensively damaged, other organs can be used to estimate age. The thymus, being retrosternal and well-protected, is easily accessible during dissection. Therefore, studying the gross features and histogenesis of the thymus can be helpful in estimating gestational age in cases of severely mutilated foetal specimens. Aim: To examine the morphological features and histogenesis of the thymus in aborted and stillborn foetuses from normal pregnancies. Materials and Methods: A pilot study was conducted using a cross-sectional design at the Department of Anatomy, BLDEDU’s Shri BM Patil Medical College, Vijayapura, Karnataka, India, from May 2016 to April 2018. The dimensions and histogenesis of the thymus were studied in a total of 50 human foetal thymus specimens, collected from normal pregnancies across different gestational age groups ranging from 12 to 40 weeks. The specimens were obtained from the Department of Pathology and the Department of Obstetrics and Gynaecology. The dimensions and weight of the thymus were recorded during autopsy. Slides were prepared, stained with Haematoxylin and Eosin (H&amp;E), and examined under a compound microscope. The histogenesis of the thymus was studied to observe its maturation. Results: Foetal weight increased from 134.6±58.3 g at 12 weeks to 1942±598 g at 40 weeks. The weight of the thymus ranged from 0.2 g at 12 weeks to 5.9 g at 40 weeks. Crown rump length varied from 10.7 cm to 29.9 cm. The length of the thymus measured between 0.5 cm and 3.3 cm, breadth between 0.4 cm and 2.3 cm, and height between 0.2 cm and 0.9 cm from 12 to 40 weeks of gestation. Microscopic features observed in the present study at different gestational ages included a well-formed thick capsule at 17 weeks, lobulation starting at 19 weeks, cortico-medullary differentiation beginning at 17 weeks, appearance of epithelial cells around 19 weeks, and initial appearance of Hassal’s corpuscles at 17 weeks, with more numbers observed later on. Conclusion: The thymus can be used in forensic investigations to estimate the gestational age of mutilated foetuses. It exhibits varying features at different gestational ages, which can aid in thymectomy procedures. Additionally, these findings can be considered during prenatal imaging studies.