京都大学 大学院医学研究科 人間健康科学系専攻 病理学研究室（形態形成医療科学）

石田さんの修士論文の一部がJ Anatomyに受諾されました

CS16からCS23までの合計47個のヒト胚の高解像度の磁気共鳴画像取得し、中腸のヘルニア期に中腸と腸間膜で時間の経過とともに生じる形態学的変化を検討、二次ループと三次ループの初期形成、それに続く追加ループの形成を正確に記載しました。この研究の知見は、ループ形成における遺伝的要因と生体力学的要因の役割を包括的に理解する上で極めて重要です。

71. Ishida N, Ueda Y, Kanahashi T, Matsubayashi J, Imai H, Yamada S, Takakuwa T.Hierarchical loop formation in human midgut during physiological umbilical herniation, J Anatomy 2024, in press DOI:10.1111/joa.14228

• CS16からCS18までのすべての標本で一次ループの形成が観察された。
• 腸間膜狭窄により中腸がを 4 つのセグメントに分割可能。
• 中腸の二次ループは、最初にCS19のセグメント2と4（S2とS4）で識別。
• 三次ループの形成は、CS21 で最初に確認
• CS23 までに、三次ループはほとんどの標本のS2,3,4のセグメントで観察
• S1は1つの二次ループのまま。
• 三次ループの数は頭殿長に応じて増加し、中腸の S2 から S4 で最大 19 個
• ループ形成における遺伝的要因と生体力学的要因の役割を包括的に理解する上で極めて重要

Abstract

The primary loop, a single hairpin-shaped loop, becomes recognizable at the Carnegie stage (CS) 16. This loop projects toward the umbilical cord and subsequently gives rise to four secondary loops in the midgut of human embryos. As development advances, the segments corresponding to each secondary loop further develop into an increasing number of loops, referred to as tertiary loops. The mesenteric leaves and the narrowing parts, which serve as the borders of the secondary loops, remain identifiable throughout the subsequent stages of development. This study aimed to describe the morphological alterations that occur in the midgut and mesentery over time during the herniated phase of the midgut. A total of 47 human embryos between CS16 and CS23 and two fetuses in the physiological umbilical herniated stage were selected for high-resolution magnetic resonance imaging acquisition. Specimens were obtained from the Congenital Anomaly Research Center of Kyoto University. Serial tissue sections obtained from four embryos were subjected to histological observation. The midgut and mesentery were reconstructed in three dimensions, and the resulting morphological changes were observed and analyzed. Formation of the primary loop was observed in all specimens between CS16 and CS18. Secondary loops in the midgut were initially discerned at CS19 in segments 2 and 4 (S2 and S4). The border between S3 and S4 was identified at the apex of the midgut hernia, where traces of the vitelline artery and duct enter the mesentery. At CS21 and later stages of development, the presence of three borders at the exact location delineated by mesenteric narrowing was consistently observed, which resulted in the midgut being divided into four segments in all specimens. The formation of tertiary loops was initially identified at Carnegie stage (CS) 21, occurring in either segment S2 or S3. By CS23, tertiary loops were observed in three segments in most specimens. Notably, the initial formation of tertiary loops in S4 occurred one Carnegie stage later than in S2 or S3. Additionally, the increase in the number of folds and the length per fold in S4 was delayed compared with the number and length of folds observed in both S2 and S3. The number of loops in S1 remained constant (one secondary loop) across all specimens. Upon reaching a critical threshold length, the number of loops exhibited a marked increase, accompanied by rapid elongation in S2, S3, and S4. The number of tertiary loops increased in accordance with the crown-rump length, which exhibited a maximum of 19 tertiary loops in S2 to S4 of the midgut. These findings support the hypothesis that tertiary loops develop biomechanically through the rapid elongation of the midgut and slow growth of the mesentery. This study describes the morphological alterations occurring in the midgut and mesentery over time during the herniated phase of the midgut and provides a comprehensive understanding of the roles of genetic and biomechanical factors in loop formation.

岩佐さんの僧帽筋形成についての論文がJ Anatomyに受諾されました。MRI_DTIを用いて僧帽筋形成過程を、外観だけでなく、椎体レベルごとの筋線維の走行まで観察しました。また、論文内の図が表紙に採用されました。

• 胎児初期におけるヒト僧帽筋（TpzM）の発達を観察し、拡散テンソル画像（DTI）分析を適用して生理機能につながる筋肉の構造を記述
• 僧帽筋はCS20で初めて検出され、その位置は、その挿入部および起始部である肩甲骨、鎖骨、および椎骨の形成とともに変化した。
• 腹側ビューでの線維配向は、挿入部が変化する中間部分を除いて、頸椎から胸椎にかけて徐々に変化し、これはすべての初期胎児標本でほぼ同じであった。
• 僧帽筋の上部では、椎骨レベルに応じて線維配向が3次元的になだらかに変化していた。

69. Iwasa Y, Kanahashi T, Imai H, Otani H, Yamada S, Takakuwa T. Human trapezius muscle development during early fetal period. J Anatomy 2024, 245, 663-673, doi: 10.1111/joa.14116

Abstract

This study aimed to observe human trapezius muscle (TpzM) development during the early fetal period and apply diffusion tensor imaging (DTI) analysis to describe the muscle architecture that leads to physiological functions. Human embryonic and early fetal specimens were selected for this study. TpzM was first detected at Carnegie stage 20. The position of the TpzM changed with the formation of the scapula, clavicle, and vertebrae, which are its insertions and origins. DTI revealed the fiber orientation from each vertebral level to dissect each muscle. Fiber orientation in the ventral view gradually changed from the cervical to thoracic vertebrae, except for the middle part at which the insertions changed, which was almost similar in all early fetal specimens. The TpzM volume increased from C1 to C7 in the upper part, reached local maxima at C6 and C7 in the middle, and then decreased. These muscles can be categorized into three parts according to their insertions and presented with the features of each part. The fiber orientation and distribution of the three parts at the vertebral level were almost constant during the early fetal period. The border between the upper and middle parts was mainly located around the C6 and C7 vertebral levels, whereas the middle and lower parts were between the Th1 and Th2 vertebral levels. A three-dimensional change in the fiber orientation in the upper part of the TpzM according to the vertebral level was noticeable. Our data will help to elucidate the developmental processes of TpzM.

磯谷さんの修士論文がAnatomical Recordに掲載されました。

胎児循環に特有の胎盤から心臓にむかう静脈路（臍帯静脈、門脈洞、静脈管、下大静脈）について、領域による特徴を高解像度デジタルデータ(MRI, CT)から得られた立体再構成像と組織像を用いて検討しました。

• 胎児循環に特有の胎盤から心臓にむかう静脈路（臍帯静脈、門脈洞、静脈管、下大静脈）について領域ごとの特徴を検討
• 胚子期から胎児期初期の29個の標本を高解像度デジタル画像化のために選択し、18個の胚を組織学的解析のために選択した。
• 領域による特徴を高解像度デジタルデータ(MRI, CT)から得られた立体再構成像と組織像を用いて検討し明らかにした。

67. Isotani N, Kanahashi T, Imai H, Yoneyama A, Yamada S, Takakuwa T. Regional differences in the umbilical vein and ductus venosus at different stages of normal human development. Anat Rec (Hoboken), 2024, 307, 3306-3326.DOI:10.1002/ar.25421

During the fetal period, oxygenated blood from the placenta flows through the umbilical vein (UV), portal sinus, ductus venosus (DV), and inferior vena cava (IVC) to the heart. This venous route varies regionally in many aspects. Herein, we sought to characterize the venous route’s morphological features and regional differences during embryonic and early-fetal periods. Twenty-nine specimens were selected for high-resolution digitized imaging; 18 embryos were chosen for histological analysis. The venous route showed a primitive, large, S-shaped curved morphology with regional narrowing and dilation at Carnegie stage (CS) 15. Regional differences in vessel-wall differentiation became apparent from approximately CS20. The vessel wall was poorly developed in most DV parts; local vessel-wall thickness at the inlet was first detected at CS20. The lumen of the venous route changed from a non-uniform shape to a relatively round and uniform morphology after CS21. During the early-fetal period, two large bends were observed around the passage of the umbilical ring and at the inlet of the liver. The length ratio of the extrahepatic UV to the total venous route increased. The sectional area gradually increased during embryonic development, whereas differences in sectional area between the DV, UV, and IVC became more pronounced in the early-fetal period. Furthermore, differences in the sectional area between the narrowest part of the DV and other hepatic veins and the transverse sinus became more pronounced. In summary, the present study described morphological, morphometric, and histological changes in the venous route throughout embryonic and early-fetal development, clarifying regional characteristics.

金橋先生の論文がCommunications Biologyに受諾されました。

ヒト胎児の骨盤形態の性差はこれまでの報告よりもずっと早く、一次骨化の開始時にすでに明らかであることを、統計学的に示しました。

*内容は、京大HP等で紹介されました

Kanahashi T, Matsubayashi J, Imai H, Yamada S, Otani H, Takakuwa T. Sexual dimorphism of the human fetal pelvis exists at the onset of primary ossification, Communications Biology, 2024, 7:538, https://doi.org/10.1038/s42003-024-06156-y

Abstract
Human adolescent and adult skeletons exhibit sexual dimorphism in the pelvis. However, the degree of sexual dimorphism of the human pelvis during prenatal development remains unclear. Here, we performed high-resolution magnetic resonance imaging-assisted pelvimetry on 72 human fetuses (males [M]: females [F], 34:38; 21 sites) with crown-rump lengths (CRL) of 50–225 mm (the onset of primary ossification). We used multiple regression analysis to examine sexual dimorphism with CRL as a covariate. Females exhibit significantly smaller pelvic inlet anteroposterior diameters (least squares mean, [F] 8.4 mm vs. [M] 8.8 mm, P = 0.036), larger subpubic angle ([F] 68.1° vs. [M] 64.0°, P = 0.034), and larger distance between the ischial spines relative to the transverse diameters of the greater pelvis than males. Furthermore, the sacral measurements indicate significant sex-CRL interactions. Our study suggests that sexual dimorphism of the human fetal pelvis is already apparent at the onset of primary ossification.