What is it about?

This study aims to understand the significance of oxytocin expression in the paraventricular hypothalamic nucleus (PVH) and supraoptic nucleus (SO), for the parturition, breastfeeding, and maternal behaviors in mice. To this end, we performed conditional knockout (cKO) of the oxytocin gene or cell ablation of oxytocin-expressing neurons in the PVH and SO. Our results showed that females with cKO of the oxytocin gene in both the PVH and SO displayed grossly normal parturition and maternal caregiving behaviors, while mothers with a smaller number of remaining oxytocin-expressing neurons exhibited severe impairments at the onset of breastfeeding. Similar observations were found in the cell ablation of oxytocin-expressing neurons, which also eliminated the secretion of other ligands from these neurons. These findings suggest that oxytocin secretion is crucial for the initiation of breastfeeding but not for the parturition or maternal caregiving behaviors. Furthermore, our cKO approach allowed us to perform oxytocin cKO in the PVH or SO separately, revealing the unequivocal role of SO-derived oxytocin in successful breastfeeding. Collectively, our findings highlight the dispensability of oxytocin for parturition or maternal behaviors, as well as the importance of SO-derived oxytocin in breastfeeding.

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Why is it important?

Parturition, lactation, and expression of parental caregiving behaviors are complex biological processes that have been believed to be critically regulated by oxytocin. However, previous studies using whole-body knockout (KO) of oxytocin have reported that only milk ejection is severely impaired, while parturition and parental behaviors appear to be less dependent on oxytocin. This could be attributed to the existence of compensatory mechanisms, whereby the absence of the oxytocin gene may enhance the expression of related gene(s) to compensate for its absence. The results reported in this paper do not support this explanation, as cKO of the oxytocin gene at the adult stage mostly recapitulated the phenotypes observed in whole-body KO. Furthermore, cell ablation of oxytocin-expressing neurons resulted in similar phenotypes to oxytocin cKO, indicating the negligible roles of non-oxytocin ligands. These results, combined with classical KO studies, suggest that oxytocin is indispensable for successful breastfeeding, but dispensable for parturition and parental behaviors. Our cKO approach allowed us to achieve single nucleus-level removal of the oxytocin gene, offering higher resolution than previous studies. Owing to this advantage, we revealed that mothers require a sufficient number of oxytocin-expressing neurons in the SO, but not in the PVH, for successful breastfeeding. These results illuminate the significance of oxytocin-expressing neurons in the SO for breastfeeding in mother mice.


We hope that this article will contribute to a deeper understanding of neural mechanisms governing parturition, breastfeeding, and parental behaviors in mammalian mothers. We also wish to elucidate the sexual dimorphism associated with oxytocin-mediated parental caregiving behaviors, as our previous study reported that father mice with oxytocin cKO in the PVH showed severe impairments in the expression of caregiving behaviors, in contrast to the normal expression of such behaviors observed in oxytocin cKO mothers in this paper. --- Kengo Inada RIKEN Center for Biosystems Dynamics Research

Kazunari Miyamichi
Riken Center for Biosystems Dynamics Research

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This page is a summary of: The importance of oxytocin neurons in the supraoptic nucleus for breastfeeding in mice, PLoS ONE, March 2023, PLOS,
DOI: 10.1371/journal.pone.0283152.
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