アクセスカウンター

2025年7月
 123456
78910111213
14151617181920
21222324252627
28293031  

奥村さんの卒研がPLoS Oneに掲載

奥村さんの卒業研究がPLoS Oneに受諾されました。

ヒトの骨格形成は、保存しやすく、レントゲンでの解析が可能な骨化中、骨化後の解析がほとんどで、軟骨形成期の解析はほとんどされていません。今回、骨盤の軟骨形成期に着目し解析を進めました。

  • CRL 12 -75 mm) の骨盤骨格における軟骨形成を検討し以下のTimeTableをえる
    • 腸骨、坐骨、および恥骨の軟骨化中心は、寛骨臼の周囲にCS18 で同時に出現し、後のステージで放射状に成長
    • 腸骨稜は CS20 で形成
    • 腸骨体は CS22 で円盤状
    • 仙腸関節は CS21で形成
    • 恥骨結合の関節接合、仙骨の関節柱の接続、寛骨臼への寛骨の 3 つの部分の Y 字型の接続はCS23 で形成
    • 坐骨と恥骨枝の接続は、胎児の初期に形成
    • 仙骨の中心での接続の程度は、標本間で異なる
  • 成長率は腸骨が恥骨、坐骨に比べて大きい
  • 小骨盤の骨盤入口の横方向および前後方向の長さ, 恥骨下の角度はCRLと相関しない。
  • 軟骨構造は、骨構造の形態に影響を与えることを示唆

28. Okumura M, Ishikawa A, Aoyama T, Yamada S, Uwabe C, Imai H, Matsuda T, Yoneyama A, Takeda T, Takakuwa T, Cartilage Formation in the Pelvic Skeleton during the Embryonic and Early-Fetal Period, PLoS One 12(4): e0173852. https://doi.org/10.1371/journal. pone.0173852 [Open Access]

Abstract

骨盤(胎児期初期)

The pelvic skeleton is formed via endochondral ossification. However, it is not known how the normal cartilage is formed before ossification occurs. Furthermore, the overall timeline of cartilage formation and the morphology of the cartilage in the pelvis are unclear. In this study, cartilage formation in the pelvic skeletons of 25 human fetuses (crown-rump length [CRL] = 11.9–75.0 mm) was observed using phase-contrast computed tomography and 7T magnetic resonance imaging. The chondrification center of the ilium, ischium, and pubis first appeared simultaneously at Carnegie stage (CS) 18, was located around the acetabulum, and grew radially in the later stage. The iliac crest formed at CS20 while the iliac body’s central part remained chondrified. The iliac body formed a discoid at CS22. The growth rate was greater in the ilium than in the sacrum-coccyx, pubis, and ischium. Connection and articulation formed in a limited period, while the sacroiliac joint formed at CS21. The articulation of the pubic symphysis, connection of the articular column in the sacrum, and Y-shape connection of the three parts of the hip bones to the acetabulum were observed at CS23; the connection of the ischium and pubic ramus was observed at the early-fetal stage. Furthermore, the degree of connection at the center of the sacrum varied among samples. Most of the pelvimetry data showed a high correlation with CRL. The transverse and antero-posterior lengths of the pelvic inlet of the lesser pelvis varied among samples (R2 = 0.11). The subpubic angle also varied (65–90°) and was not correlated with CRL (R2 = 0.22). Moreover, cartilaginous structure formation appeared to influence bone structure. This study provides valuable information regarding the morphogenesis of the pelvic structure.

吉田さんの卒論がCongenit Anomに掲載

スクリーンショット 2016-08-03 12.56.41

吉田さんの卒論がCongenit Anomに掲載されました。胎児の脳溝形成の様子をGyrification Indexを用いて解析しました。また、同号の表紙に、論文のFigureが採用されました。

  • 16 -40 週の大脳の脳溝形成について、GI値を用いて検討
  •  GI 値は、体重500g(CRL 200 mm )まで約 1.0(脳溝なし)
  • その後、GI値は体重と CRL に相関して増加(脳溝形成あり)
  • 妊娠21週で一次脳溝とGIのピークが対応
  • 31-40週数で前頭側頭領域よりも頭頂後頭領域でGI値は増加
1409g の胎児の脳の左側面図とGI値。

Gyrification index (GI) of brain slices in a left lateral view of the brain in a 1409g fetus. The line graph above the brain shows the GI of each slice below it. The GI of the whole hemisphere changed in the rostro-caudal dimension. Several maxima of the GI curve appeared in relation to gross landmarks. Further details can be seen in the article by Yoshida et al. in this issue.

27. Yoshida R, Koichi Ishizu K, Yamada S, Chigako Uwabe C, Okada T, Togashi K, Takakuwa T, The dynamics of gyrification in the human cerebral cortex during development, Congenit Anom, 57 (1) 8-14, 2017, DOI: 10.1111/cga.12179, 10.1111/cga.12181

Abstract

This study quantitatively characterized cortical gyrus folding over human neocortical development by calculating the gyrification index (GI) in 22 human fetal specimens from 16 to 40 weeks with magnetic resonance imaging data. GI values remained constant at approximately 1.0 until the fetal specimens reached 500 g body weight and 200 mm crown-rump length (CRL), respectively, and then increased in correlation with the body weight and CRL. The rostrocaudal GI distribution in the cerebral cortex revealed a correspondence of GI peaks with indentations of early-generated primary sulci at 21 weeks of gestation and more frequently increased GI values in the parieto-occipital region than in the fronto-temporal region at 31 and 40 weeks of gestation. These results provide a quantitative reference set for gyrification in normal human cortical development, which may help reveal the mechanism of neurodevelopmental disorders.

Anat Recに総説を掲載

本研究室で行われているヒト胚子・胎児研究についてまとめた総説がAnatomical Recに掲載されました。

幅広い発達期間をカバーする大規模で高解像度なデジタルデータセットの確立し、そのメリットを活かした研究展開を示しました。デジタルデータのメリット、それを活かした展開として

  • 形態計測分析に適した平面の抽出、
  • 形態学的観察の効率化。
  • 発生の特徴を定量的に評価、実証、異常なサンプルのスクリーニング
  • 超音波検査データを比較
  • 解剖学的ランドマークの 3D 座標は
  • 位置変化とそれらの関係を分析するために有用
  • 3D 座標を使用した微分成長の説明
  • 統計分析、数学的分析に応用

器官形成時の動的で複雑なプロセスの解析、正確な形態学的データの提供への寄与が期待されます。

30. Takakuwa T, 3D analysis of human embryos and fetuses using digitized datasets from the Kyoto Collection, Anat Rec 2018, 301,960-969 doi: 10.1002/ar.23784 (英文で読む)

ABSTRACT

Three-dimensional (3D) analysis of the human embryonic and early-fetal period has been performed using digitized datasets obtained from the Kyoto Collection, in which the digital datasets play a primary role in research. Datasets include magnetic resonance imaging (MRI) acquired with 1.5 T, 2.35 T, and 7 T magnet systems, phase-contrast X-ray computed tomography (CT), and digitized histological serial sections. Large, high-resolution datasets covering a broad range of developmental periods obtained with various methods of acquisition are key elements for the studies. The digital data have gross merits that enabled us to develop various analysis. Digital data analysis accelerated the speed of morphological observations using precise and improved methods by providing a suitable plane for a morphometric analysis from staged human embryos. Morphometric data are useful for quantitatively evaluating and demonstrating the features of development and for screening abnormal samples, which may be suggestive in the pathogenesis of congenital malformations. Morphometric data are also valuable for comparing sonographic data in a process known as “sonoembryology.” The 3D coordinates of anatomical landmarks may be useful tools for analyzing the positional change of interesting landmarks and their relationships during development. Several dynamic events could be explained by differential growth using 3D coordinates. Moreover, 3D coordinates can be utilized in mathematical analysis as well as statistical analysis. The 3D analysis in our study may serve to provide accurate morphologic data, including the dynamics of embryonic structures related to developmental stages, which is required for insights into the dynamic and complex processes occurring during organogenesis. Anat Rec, 301:960–969, 2018.

尾関さんの修論がAnat Recに掲載

CS22聴覚器

尾関さんの修士論文のうち、中耳耳小骨の形成と外耳、内耳との立体的位置関係についてAnat Recに掲載されました。

MEO の形成と外耳と内耳の接続のタイムラインを決定しました。

  • 軟骨頭蓋は、CS18 までに認識可能
  • 軟骨形成開始は耳小骨(MEO)間で若干の相違。
  • CS19;槌骨、キヌタ骨、アブミ骨の順序で、前後方向に配置 CS22以降;MEO同士が関節を介し接続。
  • CS21以降にすべてのMEOの軟骨形成を確認
  • CS23;アブミ骨基底部分はfoot plate状ではない
  • ツチ骨のハンドルは 外耳道からは離れている
  • 耳介軟骨と耳嚢の軟骨膜境界は明確

26. Ozeki-Satoh M, Ishikawa A, Yamada S, Uwabe C, Takakuwa T. Morphogenesis of the Middle Ear Ossicles and Spatial Relationships with the External and Inner Ears during the Embryonic Period, Anat Rec 299:1325–1337, 2016, DOI 10.1002/ar.23457

Abstract

We describe the three-dimensional morphogenesis of the middle ear ossicles (MEOs) according to Carnegie stage (CS) in human embryos. Seventeen samples including 33 MEOs from CS18 to 23 were selected from the Kyoto Collection. The primordia of the MEOs and related structures were histologically observed and three-dimensionally reconstructed from digital images. The timing of chondrogenesis was variable among structures. The stapes was recognizable as a vague condensation of the mesenchymal cells in all samples from CS18, whereas the malleus and incus were recognizable at CS19. Chondrogenesis of all MEOs was evident in all samples after CS21. The chondrocranium was recognizable in all samples by CS18, and the perichondrium border of the auricular cartilage and otic capsule was distinct in all samples at CS23. At CS19, the MEOs were positioned in the anterior to posterior direction, following the order malleus, incus, stapes, which adjusted gradually during development. The MEOs connected in all samples after CS22. The stapes was located close to the vestibular part of the inner ear, although the basal part was not differentiated into the “footplate” form, even at CS23. The handles of the malleus were close to the tubotympanic recess at CS23, but were distant from the external auditory meatus. Determining the timeline of the formation of MEOs and connection of the external and inner ears can be informative for understanding hearing loss caused by failure of this connection. These data may provide a useful standard for morphogenesis, and will contribute to distinguishing between normal and abnormal MEO development. 

Willis輪の形成についての論文Congenit Anomに掲載

Willis輪の発生(CS21); variationが多くみられる
Willis輪の発生(CS21); variationが多くみられる

ヒトのWillis輪の形成についての論文がCongenitAnomに掲載されました。
Willis輪は脳を養う血流が脳底部で輪状にあつまる部位で、成人ではvariationが多いことが知られています。
本論文では、20例の胚子期後期標本について検討し、以下の知見をえました。

  • Willis輪がCS22ころ完成すること
  • 胚子期後期でもvariationが多くみられること
  • Willis輪が未完成の標本が、成長に伴い完成したかはあきらかでないこと

25. Takakuwa T, Koike T, Muranaka T, Yamada S, Uwabe C. 2016. Formation of the circle of Willis during human embryonic development. Congenit Anom (Kyoto) 2016; 56, 233–236, DOI: 10.1111/cga.12165

Abstract

The circle of Willis (CW) is a circulatory anastomosis that supplies blood to the brain and adjacent structures. We examined the timing of formation of CW in 20 Japanese human embryo samples by using 3-dimensional reconstruction of serial histological sections. The CW was closed in 1 (n = 6), 2 (n = 8), 2 (n = 3) and 2 (n = 3) samples at Carnegie stages 20, 21, 22, and 23, respectively. The CW was unclosed in 13 samples (unclosed at ACOM alone, 6 samples; ACOM and bilateral P1, 4; left PCOM and right P1, 1; right PCOM and right P1, 1; ACOM and left PCOM, 1). It was difficult to predict whether the circle would close during further development, as such variations frequently exist in adults.

小林さんの卒論がPrenatal Diagnosisに掲載&表紙に採用

pd4818-toc-0001

小林さんの卒論がPrenatal Diagnosisに掲載されました。ヒト胚子期の標本を用いて脳の発生に伴う計測値の変化、特徴を論じたものです。

  • 胚子期の標本の脳の7直線、3領域の面積、体積を検討
  • すべての直線計測値はCRLと相関
  • bitemporal lengthと全脳、大脳体積は高い相関

得られた結果は、超音波データの修正と比較、出生前診断の改善に貢献することが期待されます。

また、同号の表紙にも採用されました。

23. Kobayashi A, Ishizu K, Yamada S, Uwabe C, Kose K, Takakuwa T, Morphometric human embryonic brain features according to developmental stage, Prenatal Diagnosis, 36:338–345, 2016, DOI: 10.1002/pd.4786. DOI: 10.1002/pd.4818

Abstract

Objectives

The present study investigated linear, area, and volume measurements of human brain samples according to Carnegie stages (CS) in an attempt to select suitable morphometric features that reflect embryonic development.

Methods

Using magnetic resonance imaging, we measured seven linear segments, three separate areas, and three regional volumes in 101 samples between CS13 and 23. Brain volume was determined via manual segmentation of the magnetic resonance image, whereby a formula was generated to estimate the volume of each linear measurement.

Results

All parameters correlated with crown-rump length. Bitemporal length and mesencephalic height increased linearly according to the CS, and a high correlation between bitemporal length and both whole-brain (r = 0.98) and prosencephalon (r = 0.99) volumes was found when brain cavity volume was excluded.

Conclusion

Morphometric data related to human embryonic stages are valuable for correcting and comparing sonographic data. The present approach may contribute to improvements in prenatal diagnostics by enabling the selection of more suitable measurements during early embryonic stages.

上野さんの修論がAnat Recに掲載

上野さんの修論がAnat Recに掲載されました。

Somite stageの胚(CS11-13, 28-33日, 21−35体節)における消化管由来原基の形態と分化のTimeLineを検討

  • 消化管と派生した原基は、以下のTimelineに従って発生し、個人差が少ないことを示唆
    • 消化管は最初、卵黄嚢の狭小化によって形成される
    • 咽頭、肺、胃、肝臓、および背側膵臓原基; CS12-13 の間に分化
    • 咽頭嚢; 4 つのペアの分化は、すべての CS13 胚で完了
    • 呼吸原基; ≥ 26 体節胚で認められ、CS13 で気管分岐が形成、≥ 35 体節胚で気管伸長。
    • 胃; ≥ 34 体節胚で紡錘形
    • 肝芽は ≥ 27 体節胚で確認
    • 背側膵臓は、3 つを除くすべての CS13 胚で最終的な出芽
    • 原始腸ループ ≥ 35 体節の胚形成

今後、消化管関連の異常発生の検出等に有用と考えられます。

CS12-13

22. Ueno S, Yamada S, Uwabe C, Männer J, Shiraki N, Takakuwa T, The digestive tract and derived primordia differentiate by following a precise timeline in human embryos between Carnegie stages 11 and 13, Anatomical Rec 2016, 299(4), 439-449, DOI: 10.1002/ar.23314

ABSTRACT

The precise mechanisms through which the digestive tract develops during the somite stage remain undefined. In this study, we examined the morphology and precise timeline of differentiation of digestive tract-derived primordia in human somite-stage embryos. We selected 37 human embryos at Carnegie Stage (CS) 11–CS13 (28–33 days after fertilization) and three-dimensionally analyzed the morphology and positioning of the digestive tract and derived primordia in all samples, using images reconstructed from histological serial sections. The digestive tract was initially formed by a narrowing of the yolk sac, and then several derived primordia such as the pharynx, lung, stomach, liver, and dorsal pancreas primordia differentiated during CS12 (21–29 somites) and CS13 (≥ 30 somites). The differentiation of four pairs of pharyngeal pouches was complete in all CS13 embryos. The respiratory primordium was recognized in ≥ 26-somite embryos and it flattened and then branched at CS13. The trachea formed and then elongated in ≥ 35-somite embryos. The stomach adopted a spindle shape in all ≥ 34-somite embryos, and the liver bud was recognized in ≥ 27-somite embryos. The dorsal pancreas appeared as definitive buddings in all but three CS13 embryos, and around these buddings, the small intestine bent in ≥ 33-somite embryos. In ≥ 35-somite embryos, the small intestine rotated around the cranial-caudal axis and had begun to form a primitive intestinal loop, which led to umbilical herniation. These data indicate that the digestive tract and derived primordia differentiate by following a precise timeline and exhibit limited individual variations. 

尾関さんの修論が Congenit Anomに掲載

名称未設定

尾関さんの修士論文のうち、ヒト外耳の形態形成に関する内容がCongenit Anom (日本先天異常学会誌)に受諾されました。500例以上の外耳観察の成果です。

  • CS19-23 間の耳介の形成を検討
  • 耳介をStreeter の基準に修正を加えて 11 stepに分類
  • 各 CS の代表的なstepは、CS16-23 の間にstep 3 -11 に移行、
  • いくつかのステップでは隣接する CS 間で重複
  • CS19 と CS23 の間の耳介の観察は、Stagingを決定するために利用可能

21. Ozeki-Sato M, Yamada S, Uwabe C, Ishizu K, Takakuwa T, Correlation of external ear auricle formation with staging of human embryos, Congenit Anom (Kyoto) 56, 86-90, 2016, DOI: 10.1111/cga.12140, . (概要),

Abstract

The formation of auricles in human embryos was evaluated between Carnegie stage (CS)19 and CS23, and the findings were correlated across the stages. The auricle was categorized into 11 steps according to Streeter’s criteria with modifications. Mesenchyme cell condensation was observed at Step 7, and two layers of cartilage consisting of the auricle were recognized at Step11. The representative steps at each CS shifted from Step 3 to Step11 during CS16 and CS23, although several steps overlapped between adjacent CSs. These results indicate that observations of the auricle between CS19 and CS23 may be utilized for determining embryo staging as convincing supportive evidence of external features reflecting the internal histological structure, although other findings should also be taken into account.