Role of serotonin in human placental cytotrophoblast differentiation and gene expression

Serotonin (5-hydroxytryptamine; 5-HT) is transported into the human placenta through the serotonin transporter (SERT/SLC6A4) on the surface of the syncytiotrophoblast, where it ultimately makes its way to the circulation within the conceptus. During this transit a significant amount of 5-HT becomes concentrated in the cytotrophoblast nucleus. We used immunochemistry, inhibitors of SERT and transglutaminase 2 (TGM2; the enzyme that mediates the covalent linkage of 5-HT to protein glutamine residues—a process known as serotonylation), 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. Inhibiting SERT with escitalopram or TGM2 with cystamine blocked cytotrophoblast differentiation in vitro; namely, flattening, aggregation and forming syncytia. Cystamine eliminated the staining of the ..., Specimens
Term placentas were collected anonymously from patients undergoing elective repeat Cesarian sections who delivered healthy babies. All the women who provided term placental samples signed an informed consent (Yale IRB protocol 1208010742).
Trophoblast Purification
Cytotrophoblast were prepared from fresh human term placentas by trypsin digestion and Percoll gradient fractionation, with the addition of an anti-CD9 and CD45 magnetic bead purification step, as previously described (1,2). During the initial steps of the digestions and up to the magnetic purification step, 10% fetal bovine serum (FBS, Gemini Bio-Products, Broderick, CA, 100-106) diluted in DMEM/F12 (Gibco, ThermoFisher Scientific, Waltham, MA, 11330-032) with 4 mM L-glutamine, 1% penicillin/streptomycin was utilized. After the magnetic purification step, no FBS was added to the culture media, unless specifically noted. Cytotrophoblasts were then diluted to 1x106 cells per ml in DMEM/F12 with 4 mM L-glutamine, 1% pe..., # Data from: Role of serotonin in human placental cytotrophoblast differentiation and gene expression

Dataset DOI: [10.5061/dryad.b8gtht7qb](10.5061/dryad.b8gtht7qb)

## Description of the data and file structure

This README_Kliman_29Jul2025_Endocrinolgy_DATA.txt file was generated on 6Apr2025, and updated on 29Jul25, by Harvey J. Kliman, MD, PhD 

**GENERAL INFORMATION**

1\. Title of Dataset: Endocrinology-S-25-00232 files

2\. Author Information

* Harvey J. Kliman, MD, PhD
* Yale University School of Medicine
* [[e-mail]](mailto:[e-mail])

 

* Nolwenn S. Morris, PhD
* Yale University School of Medicine
* [[e-mail]](mailto:[e-mail])

 

3\. Date of data collection: 2024

4\. Geographic location of data collection: New Haven, CT, USA

5\. This work was supported by the Fulbright-Monahan Foundation (NSM), the University of Paris (NSM), and the Reproductive and Placental Research Unit, Yale University School of Medicine ..., Term placentas were collected anonymously from patients undergoing elective repeat Cesarian sections who delivered healthy babies. All the women who provided term placental samples signed an informed consent (Yale IRB protocol 1208010742). All data has been de-identified.