2. Academic Validation
  3. Effect and mechanism of maternal prolactin levels on depressive-like behavior in prenatally stressed offspring

Effect and mechanism of maternal prolactin levels on depressive-like behavior in prenatally stressed offspring

  • Int J Biol Macromol. 2026 Jan;340(Pt 1):150002. doi: 10.1016/j.ijbiomac.2025.150002.
Hui Zhao 1,  Zheng Gong 2,  Mingxia Zhang 3,  Huan Guo 2,  Tu Chen 2,  Yuting Zhao 2,  Xiaoqing Du 2,  Siyu Chen 2,  Jiaqi Jiang 4,  Leijing Zhu 4,  Xinyi Ma 2,  Jiajia Liu 2,  Hui Li 4,  Yushan Lu 5,  Zhongliang Zhu 6
Affiliations

Affiliations

  • 1 Institute of Maternal and Infant Health, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, 710069, China; Clinical Experimental Center, Northwest University Affiliated Xi'an International Medical Center Hospital, Xi'an, 710100, China.
  • 2 Institute of Maternal and Infant Health, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, 710069, China.
  • 3 Clinical Experimental Center, Northwest University Affiliated Xi'an International Medical Center Hospital, Xi'an, 710100, China.
  • 4 Department of Neonatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
  • 5 The Key Laboratory for Screening and Diagnosis of Maternal and Child Genetic Disease of Health Commission of Jiangxi Province, Jiujiang Maternal and Child Care Centres, Jiujiang, 332000, China. Electronic address: [email protected].
  • 6 Institute of Maternal and Infant Health, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, 710069, China; Jiujiang Clinical Research Center for Children's Brain and Intellectual Development, Jiujiang Maternal and Child Care Centres, Jiujiang, 332000, China. Electronic address: [email protected].
PMID: 41485664 DOI: 10.1016/j.ijbiomac.2025.150002
Abstract

Prenatal stress (PS) has an adverse impact on the neurodevelopment of the fetus and increases the risk of depression in offspring. Prolactin (PRL), a polypeptide hormone released by the pituitary gland, has a promising neuroprotective effect. However, it is not clear whether the decline in PRL levels during gestation is related to the depressive-like behavior of offspring caused by PS. This study aimed to assess the role and mechanism of PRL during gestation on depressive-like behavior in PS offspring rats. We found that PS led to a marked decrease in serum PRL levels of the maternal rats, accompanied by depressive-like behavior in offspring rats. Exogenous PRL supplementation during pregnancy significantly mitigated depressive-like behavior, ameliorated neuronal damage and neuroinflammation, and restored synaptic plasticity in the medial prefrontal cortex (mPFC) of PS offspring rats. Further investigation confirmed that PRL exerted a neuroprotective effect by activating the cAMP signaling in the mPFC of PS offspring rats. Single cell RNA (scRNA) Sequencing revealed that PRL administration during pregnancy resulted in the alterations of immune cell proportions, such as microglia, granulocytes, and B cells. Further analysis of microglia found that the differentially expressed genes (DEGs) in microglia were involved in multiple immune-related signaling pathways. Meanwhile, PRL intervention switched microglial polarization toward the M2 phenotype in PS offspring rats. Additionally, PRL administration during pregnancy effectively ameliorated gut microbiota disturbances in PS offspring rats. Our findings proposed that PRL administration during pregnancy could significantly mitigate depressive-like behavior in PS offspring rats by modulating cAMP signaling-mediated synaptic plasticity, facilitating microglial M2 polarization, and ameliorating gut microbiota dysbiosis.

Keywords

Depression; Gut microbiota; Microglia; Prenatal stress; Prolactin; cAMP.

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