大口 昭英

The villous trophoblast cells are of fundamental importance because they fulfill a variety of functions that are vital for the growth of the fetus and the maintenance of pregnancy. A simple in vitro villous trophoblast cell model that grows on standard tissue culture plates has been utilized for various functional studies on villous trophoblast cells. Despite the potential value of incorporating electron microscopy analysis in reports on functional analysis of primary human trophoblast cells, electron microscopy analysis is exclusively ancillary to functional analysis in previous publications. In the context of autophagy research of villous trophoblast cells using primary trophoblast cells, a detailed ultrastructural analysis of autophagy flux using electron microscopy is imperative; however, it has not been conducted to date. In this study, we isolated term villous trophoblast cells (i.e., cytotrophoblast cells, CTB cells) using the most up-to-date isolation method for isolating pure CTB cells from human term placenta and investigated the ultrastructural dynamic process of autophagy of cultured CTB cells by means of transmission electron microscopy. The initial 6 h culture resulted in CTB cell aggregation; however, the majority of CTB cells did not differentiate into syncytial cells. In contrast, after 72 h, CTB cells exhibited a promotion of differentiation into syncytial cells. The electron microscopy analysis revealed the upregulation of autophagy and visualized unique autophagic profiles during differentiation into syncytial cells, which exhibited perinuclear accumulation of extremely large autophagosomes/autolysosomes. This study provides novel insights into the reproductive biology of primary trophoblast cells, thereby demonstrating the substantial value of primary trophoblast cells as research resources.

AIM: We reviewed case reports of acute fatty liver of pregnancy (AFLP) in Japan and summarized its characteristics, including coagulation factors, fibrinolytic factors, and platelet counts. METHODS: PubMed/Medline and Ichushi databases from 2000 to 2022 were used to survey articles related to AFLP, and 93 articles (102 patients) were ultimately identified. RESULTS: The characteristics of the coagulation and fibrinolysis systems in AFLP were as follows: the prothrombin time-international normalized ratio and activated partial prothrombin time were prolonged (median value [quartiles]: 1.59 [1.31, 2.02] and 47.5 s [28.2, 97.5], respectively), and antithrombin and alpha 2-antiplasmin levels were low (23.0% [17.0, 33.0] and 44.6%, respectively), indicating non-productive coagulopathy due to severe liver damage. The concentrations of the thrombin-antithrombin complex and fibrinogen/fibrin degradation products were high (60.0 ng/mL [49.1, 82.8] and 49.2 μg/mL [20.8, 143.7], respectively), while the level of fibrinogen was low (82.0 mg/dL [52.5, 153.5]), suggesting disseminated intravascular coagulation with increased coagulation activity. A platelet count ≥12 × 104/μL was detected in approximately 70% of AFLP cases, and the median was within the normal range (16.1 × 104/μL [11.1, 19.2]). CONCLUSIONS: Coagulopathy changes in AFLP may be based on non-productive coagulopathy of coagulation and fibrinolytic factors as well as disseminated intravascular coagulation with mild or no thrombocytopenia.

クラスIIリボヌクレアーゼIIIであるDROSHAは、古典的機能であるprimary microRNAプロセシング酵素として知られているが、多彩なRNA代謝に関連する機能(非古典的機能)を有している。ヒト胎盤絨毛の表面を覆い、母体血に接している合胞体栄養膜細胞は、ウイルス垂直感染に対して高い抵抗性を持つバリアとして機能している。ウイルス感染防御のための多彩な武器(パターン認識受容体、インターフェロン、胎盤特異的microRNA、DROSHAによるウイルスRNAのクランプなど)を持ち、ウイルスの垂直感染を防いでいる。本稿では、DROSHAの機能、胎盤絨毛栄養膜細胞のウイルス感染防御について概説する。(著者抄録)