A brain locus for viable gestation
- 1Departments of Psychiatry and Behavioral Sciences; Neurobiology; Obstetrics and Gynecology, Stanford University
Abstract
The expectant mother's body is systemically remodeled by her hormones to weather the physiological vicissitudes of pregnancy. In contrast to other reproductive organs, how the expectant mother's brain promotes these system-wide changes is largely unexplored. Here we show that pregnancy induces profound changes in gene expression and identity of hormone-sensitive neurons and report a previously unknown class of such cells that is required for viable pregnancy. We performed RNA sequencing from late mid-gestation mice of four estrogen receptor alpha-expressing populations from hypothalamus and amygdala that regulate reproductive behaviors altered during gestation. Each of these populations undergoes such large, specific transcriptional shifts during pregnancy that these changes even exceed their transcriptional differences between the sexes. The gene expression changes during pregnancy also imbue particular transcriptomically-defined neuronal types within these four populations with new molecular identities. Targeted ablation of one such neuronal type, POANpy2r cells, precludes implantation and abrogates viable pregnancy. Taken together, we have uncovered an essential role of hormone-sensitive neurons in the brain in sustaining pregnancy. The etiology of spontaneous gestational loss, which afflicts ~15% of human pregnancies, remains idiopathic in many cases, and our findings suggest a brain-based mechanism that contributes to such events. More broadly, we provide a molecular and cellular foundation to study gestational processes in health and disease from the perspective of the pregnant brain-body axis.
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BibTeX
@misc{tanaka2026brain,
title = {{A brain locus for viable gestation}},
author = {S. Tanaka and J. R. Knoedler and V. Miessler de Andrade Carvalho and M. Alvarado Mandujano and Y. Wei and R. Yang and A. Tantry and S. A. E. Pilapitiya and B. Parasar and M. Wang and C.-h. O. Davis and L. Cui and M. H. Foecke and D. J. Laird and L. Tan and N. M. Shah},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.15.751878},
url = {https://www.biorxiv.org/content/10.64898/2026.09.15.751878v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A brain locus for viable gestation
AU - S. Tanaka
AU - J. R. Knoedler
AU - V. Miessler de Andrade Carvalho
AU - M. Alvarado Mandujano
AU - Y. Wei
AU - R. Yang
AU - A. Tantry
AU - S. A. E. Pilapitiya
AU - B. Parasar
AU - M. Wang
AU - C.-h. O. Davis
AU - L. Cui
AU - M. H. Foecke
AU - D. J. Laird
AU - L. Tan
AU - N. M. Shah
PY - 2026
DA - 2026/09/15
PB - bioRxiv
DO - 10.64898/2026.09.15.751878
UR - https://www.biorxiv.org/content/10.64898/2026.09.15.751878v1
AB - The expectant mother's body is systemically remodeled by her hormones to weather the physiological vicissitudes of pregnancy. In contrast to other reproductive organs, how the expectant mother's brain promotes these system-wide changes is largely unexplored. Here we show that pregnancy induces profound changes in gene expression and identity of hormone-sensitive neurons and report a previously unknown class of such cells that is required for viable pregnancy. We performed RNA sequencing from late mid-gestation mice of four estrogen receptor alpha-expressing populations from hypothalamus and amygdala that regulate reproductive behaviors altered during gestation. Each of these populations undergoes such large, specific transcriptional shifts during pregnancy that these changes even exceed their transcriptional differences between the sexes. The gene expression changes during pregnancy also imbue particular transcriptomically-defined neuronal types within these four populations with new molecular identities. Targeted ablation of one such neuronal type, POANpy2r cells, precludes implantation and abrogates viable pregnancy. Taken together, we have uncovered an essential role of hormone-sensitive neurons in the brain in sustaining pregnancy. The etiology of spontaneous gestational loss, which afflicts ~15% of human pregnancies, remains idiopathic in many cases, and our findings suggest a brain-based mechanism that contributes to such events. More broadly, we provide a molecular and cellular foundation to study gestational processes in health and disease from the perspective of the pregnant brain-body axis.
ER -