2025-09-03 イェール大学
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<関連情報>
- https://news.yale.edu/2025/09/03/serotonin-shield-placentas-critical-role-health-babies
- https://academic.oup.com/endo/article/166/9/bqaf124/8244922
- https://news.yale.edu/2006/06/26/key-early-diagnosis-autism-may-be-placenta
自閉症早期診断の鍵は胎盤にある可能性 Key to Early Diagnosis of Autism May be in the Placenta
Nolwenn S Morris, Seth Guller, Zhonghua Tang, Yuan-Wei Zhang, Erin C Siegman, Kristin M Milano, Gary Rudnick, Harvey J Kliman
Endocrinology Published:03 September 2025
DOI:https://doi.org/10.1210/endocr/bqaf124
Abstract
Serotonin (5-hydroxytryptamine; 5-HT) is transported into the human placenta through the serotonin transporter (SERT/SLC6A4) on the surface of the syncytiotrophoblast. During this transit, a significant amount of 5-HT becomes concentrated in the cytotrophoblast nucleus. We used immunochemistry, inhibitors of SERT and transglutaminase 2, and RNA sequencing to elucidate the mechanism and consequences of this nuclear localization. Exogenous 5-HT recapitulated the uptake of 5-HT into the trophoblasts and its preferential concentration in cytotrophoblast nuclei we observed in the intact placenta. Cystamine eliminated the staining of the nuclei in placental explants by exogenous 5-HT, suggesting that serotonylation mediated this phenomenon. This was confirmed by Western blots and immunoprecipitation that identified histone 3, and specifically the 5th glutamine residue in histone 3, as a site of serotonylation. Inhibiting SERT with escitalopram or transglutaminase 2 with cystamine blocked cytotrophoblast differentiation in vitro and led to marked changes in RNA expression. Of the 38 524 mRNAs identified in these trophoblasts, cystamine changed the expression of 1986 and escitalopram significantly altered 374. Both treatments altered the expression of 155 mRNAs either positively or negatively. The downregulated genes were involved with cell proliferation, morphogenesis, motility, and growth, whereas genes that were upregulated controlled cell survival and protection pathways. These findings suggest that maternal 5-HT promotes placental, embryonic/fetal, and organismal development through histone serotonylation and consequent alterations in gene expression. They raise the possibility that alterations in 5-HT flux in the placenta affect placental and fetal growth, as well as organismal somatic, neurologic developmental, and pathological trajectories.
自閉症スペクトラム障害における胎盤栄養膜包涵体 Placental Trophoblast Inclusions in Autism Spectrum Disorder
George M. Anderson ∙ Andrea Jacobs-Stannard ∙ Katarzyna Chawarska ∙ Fred R. Volkmar ∙ Harvey J. Kliman
Biological Psychiatry Published:June 24, 2006
DOI:https://doi.org/10.1016/j.biopsych.2006.03.068
Abstract
Background
Microscopic examination of placental tissue may provide a route to assessing risk and understanding underlying biology of autism.
Methods
Occurrence of a distinctive microscopic placental morphological abnormality, the trophoblast inclusion, was assessed using archived placental tissue. The rate of occurrence of trophoblast inclusion-positive slides observed for 13 individuals with autism spectrum disorder (ASD) was compared to the rate in an anonymous consecutive birth cohort.
Results
The occurrence of inclusion positive slides was significantly greater in the ASD group compared to the control group (6/27 slides, 22.2% vs. 12/154, 7.8%; Fisher Exact Test, two-tailed p = .033; relative risk 2.85). The proportion of positive cases was also greater in the ASD group (5/13 cases, 38.5% vs. 8/61, 13.1%; Fisher Exact, two-tailed p = .044; relative risk 2.93). Behavioral severity scores did not differ across groups of inclusion positive (N = 4) and negative (N = 8) ASD individuals.
Conclusions
Although probably not functionally detrimental or causative, the greater occurrence of placental trophoblast inclusions observed in ASD individuals may reflect altered early developmental processes. Further research is required to replicate the basic finding, to understand the basis for the trophoblastic abnormality, and to determine the utility of the measure in early detection of ASD.
