TPH1-dependent maternal hyposerotonemia: long-term effects on adult wild-type mouse offspring

Abstract

Numerous mood and behavior disorders have developmental origins resulting from genetic and environmental interactions. Maternal tryptophan hydroxylase 1 (TPH-1)-dependent serotonin (5-HT) depletion alters embryonic brain development, but its long-term impact on adult progeny has never been investigated. Here we demonstrate that adult WT male offspring born to hyposerotonergic Tph1+/- dams (~60% deficit) display hyperlocomotion, impaired self-care and an increased anxiety relative to those from WT dams. Concomitantly, norepinephrine (NE) levels and dopamine (DA) turnover are significantly reduced in the mesencephalon and brainstem, whereas monoaminergic cell density is not affected. In the frontal cortex of the offspring, maternal hyposerotonergic status results in significant reduction in DA, NE and 5-HT levels, accompanied by transcriptomic changes, notably in monoaminergic system signaling, synaptic function and plasticity, methylation processes and myelination. Myelination is also impaired as revealed by a reduced thickness of the corpus callosum. Maternal hyposerotonemia thus appears sufficient to affect the phenotype of the adult WT progeny. TPH-1-dependent 5-HT deficit during pregnancy could be considered as a risk factor for neurodevelopmental disorders in the offspring.

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BibTeX RIS

BibTeX

@article{saurini2026tph1dependent,
  title = {{TPH1-dependent maternal hyposerotonemia: long-term effects on adult wild-type mouse offspring}},
  author = {Françoise Saurini and Carolina Jaliffa and Gwenaëlle Le Pen and Chantal Joubert and Jacques Callebert and Jean-Marie Launay and Catherine Senamaud-Beaufort and Oumy Seydi and Pierre Gressens and Guilan Vodjdani and Sylvie Berrard and Tania Vitalis},
  journal = {Communications Biology},
  year = {2026},
  month = jun,
  doi = {10.1038/s42003-026-10549-6},
  url = {https://hal.science/hal-05723363v1},
  note = {CC BY-NC-ND 4.0},
}

RIS

TY  - JOUR
TI  - TPH1-dependent maternal hyposerotonemia: long-term effects on adult wild-type mouse offspring
AU  - Françoise Saurini
AU  - Carolina Jaliffa
AU  - Gwenaëlle Le Pen
AU  - Chantal Joubert
AU  - Jacques Callebert
AU  - Jean-Marie Launay
AU  - Catherine Senamaud-Beaufort
AU  - Oumy Seydi
AU  - Pierre Gressens
AU  - Guilan Vodjdani
AU  - Sylvie Berrard
AU  - Tania Vitalis
PY  - 2026
DA  - 2026/06/24
JO  - Communications Biology
DO  - 10.1038/s42003-026-10549-6
UR  - https://hal.science/hal-05723363v1
AB  - Numerous mood and behavior disorders have developmental origins resulting from genetic and environmental interactions. Maternal tryptophan hydroxylase 1 (TPH-1)-dependent serotonin (5-HT) depletion alters embryonic brain development, but its long-term impact on adult progeny has never been investigated. Here we demonstrate that adult WT male offspring born to hyposerotonergic Tph1+/- dams (~60% deficit) display hyperlocomotion, impaired self-care and an increased anxiety relative to those from WT dams. Concomitantly, norepinephrine (NE) levels and dopamine (DA) turnover are significantly reduced in the mesencephalon and brainstem, whereas monoaminergic cell density is not affected. In the frontal cortex of the offspring, maternal hyposerotonergic status results in significant reduction in DA, NE and 5-HT levels, accompanied by transcriptomic changes, notably in monoaminergic system signaling, synaptic function and plasticity, methylation processes and myelination. Myelination is also impaired as revealed by a reduced thickness of the corpus callosum. Maternal hyposerotonemia thus appears sufficient to affect the phenotype of the adult WT progeny. TPH-1-dependent 5-HT deficit during pregnancy could be considered as a risk factor for neurodevelopmental disorders in the offspring.
SN  - 2399-3642
ER  -

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