Maternal serotonin transporter genotype influences offspring’s anxiety-like behavior through prenatal and early postnatal routes
Year: 2026
Type: article
Abstract: Maternal serotonin transporter (5-HTT) genotype has been linked to offspring’s risk for neuropsychiatric disorders, yet the contribution of prenatal versus early postnatal routes remains unresolved. We combined a 5-HTT −/− rat model with a fostering procedure to disentangle these effects. 5-HTT +/− offspring genotype was kept constant by crossing 5-HTT −/− or 5-HTT +/+ dams with males of opposite genotypes. Prenatally, compared with 5-HTT +/+ dams, 5-HTT −/− dams produced smaller embryos with impaired serotonergic maturation. Their placentas exhibited alterations in serotonergic-related signaling. Postnatally, 5-HTT −/− dams exhibited reduced licking and grooming. Adult offspring from 5-HTT −/− dams showed lower anxiety-like behavior alongside altered corticosterone recovery following stress and elevated infralimbic Gad67 expression relative to offspring from 5-HTT +/+ dams. To dissociate prenatal from postnatal influences, offspring were cross-fostered with genotype-mismatched dams. Under cross-fostering, offspring from 5-HTT −/− dams exhibited a higher serotonin/tryptophan ratio and reduced Bdnf isoform VI expression in the medial prefrontal cortex compared to offspring from 5-HTT +/+ dams. Independent of biological dam genotype, cross-fostering reduced body weight, increased anxiety-like behavior, and downregulated HPA-axis- and GABA/glutamatergic-related signaling. Here, we demonstrate that maternal 5-HTT genotype shapes offspring’s anxiety-like behavior through combined prenatal and early postnatal effects, highlighting the intertwined roles of maternal genetics and environment in neuropsychiatric disorders' pathophysiology.
Source: Scientific Reports
Authors: Rogério C. R. Castro, Sabrina I. Hanswijk, Paola Brivio, Weizhuo Li, Brianna N. Natale, Sylvia Docq, Lisa C. M. W. Heltzel, Xianzong Meng, Qiuyuan Fang, Celine A. J. Smits, Deborah G. A. Peeters, Marloes J. A. G. Henckens, Roel Vrooman, Anthonieke Middelman, Petronella D. H. van den Burg, Petra H. H. van den Broek, Rick Greupink, Marcia Spoelder, Marta C. F. Samina, Tianhua Wang, Markus Wöhr, Ling Shan, Michel M. M. Verheij, Sharon M. Kolk, Chunqing Liu, Jan K. Buitelaar, Francesca Calabrese, Judith R. Homberg
Institutions: Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, University of Milan, Dalian Medical University, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Donders Centre for Neuroscience, Philipps University of Marburg, KU Leuven, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Awards: SoundsGood! – An integrated platform for studying ultrasonic vocalizations in rodent models for brain disorders., G3345895242, G3443849562, G5463179174, Deciphering socio-affective communication through ultrasonic vocalizations in rodents: Improving translational research models for neuropsychiatric dysfunctions., G5998035708, G7984235579, G8629366956, SoundsGood! – An integrated platform for studying ultrasonic vocalizations in rodent models for brain disorders.
OpenAlex ID: W7203878419
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