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Papel de la serotonina en la expresión génica y la fisiología en los citotrofoblastos humanos y la placenta
Nolwenn S Morris1,2, Seth Guller1, Zhonghua Tang1
1Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
Endocrinology
|September 3, 2025
Resumen
La serotonina materna (5-hidroxitriptamina; 5-HT) se concentra en los núcleos placentarios, donde modifica la histona 3 a través de la serotonilación. Este proceso influye en la expresión génica, impactando el desarrollo placentario y fetal.
Área de la Ciencia:
- Biología de la reproducción
- Biología del desarrollo
- La bioquímica
Sus antecedentes:
- La serotonina (5-hidroxitriptamina; 5-HT) es transportada a las células placentarias humanas a través del transportador de serotonina (SERT/ SLC6A4).
- Una porción significativa de 5-HT se acumula dentro del núcleo citotrofoblástico.
Objetivo del estudio:
- Investigar el mecanismo y las consecuencias de la localización nuclear de 5-HT en la placenta.
- Determinar si la modificación de histonas por 5-HT influye en el desarrollo placentario y fetal.
Principales métodos:
- Estudios inmunoquímicos y explantes placentarios con 5-HT exógeno.
- Inhibición de la SERT (escitalopram) y de la transglutaminasa 2 (cistamina).
- Secuenciación de ARN y análisis de Western blot para identificar modificaciones histónicas y cambios en la expresión génica.
Principales resultados:
- 5-HT exógeno concentrado en núcleos citotrofoblásticos, un proceso inhibido por la cistamina, indicando la serotonilación.
- La histona 3 fue identificada como un sitio de serotonilación en el residuo de glutamina 5.
- La inhibición de la SERT o de la transglutaminasa 2 alteró la diferenciación de los citotrofoblastos y alteró la expresión de numerosos genes implicados en el desarrollo y la supervivencia.
Conclusiones:
- La 5-HT materna promueve el desarrollo placentario, embrionario / fetal y del organismo a través de la serotonilación de histonas.
- El flujo placentario alterado de 5-HT puede afectar el crecimiento fetal y las trayectorias del desarrollo neurológico.
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