Sensory neuron LKB1 mediates ovarian and reproductive function

Abstract Treatments for reproductive disorders in women consist of hormone replacement therapy, which have negative side effects that impact health, spurring the need to understand new mechanisms to employ new therapeutic strategies. Bidirectional communication between sensory neurons and the organs...

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Main Authors: Melissa E Lenert, Emily K Debner, Michael D Burton
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-024-79947-2
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author Melissa E Lenert
Emily K Debner
Michael D Burton
author_facet Melissa E Lenert
Emily K Debner
Michael D Burton
author_sort Melissa E Lenert
collection DOAJ
description Abstract Treatments for reproductive disorders in women consist of hormone replacement therapy, which have negative side effects that impact health, spurring the need to understand new mechanisms to employ new therapeutic strategies. Bidirectional communication between sensory neurons and the organs they innervate is an emerging area of interest in tissue physiology with a relevance in reproductive disorders. We hypothesized that the metabolic activity of sensory neurons has a profound effect on reproductive phenotypes. To investigate this phenomenon, we utilized a murine model with conditional deletion of liver kinase B1 (LKB1), a serine/threonine kinase that regulates cellular metabolism in sensory neurons (Nav1.8cre; LKB1fl/fl). LKB1 deletion in sensory neurons resulted in reduced ovarian innervation from dorsal root ganglia neurons and increased follicular turnover compared to littermate controls. Female mice with this LKB1 deletion had significantly more pups per litter compared to wild-type females. Interestingly, the LKB1 genotype of male breeders had no effect on fertility outcomes, thus indicating a female-specific role of sensory neuron metabolism in fertility. In summary, LKB1 expression in peripheral sensory neurons plays an important role in modulating fertility of female mice via ovarian sensory innervation.
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spelling doaj-art-a5cb9a5eb57d4fb18594db7d75eef4f22025-08-20T02:51:15ZengNature PortfolioScientific Reports2045-23222024-11-0114111710.1038/s41598-024-79947-2Sensory neuron LKB1 mediates ovarian and reproductive functionMelissa E Lenert0Emily K Debner1Michael D Burton2Neuroimmunology and Behavior Laboratory, Department of Neuroscience, School of Behavioral and Brain Sciences, Center for Advanced Pain Studies (CAPS), The University of Texas at DallasNeuroimmunology and Behavior Laboratory, Department of Neuroscience, School of Behavioral and Brain Sciences, Center for Advanced Pain Studies (CAPS), The University of Texas at DallasNeuroimmunology and Behavior Laboratory, Department of Neuroscience, School of Behavioral and Brain Sciences, Center for Advanced Pain Studies (CAPS), The University of Texas at DallasAbstract Treatments for reproductive disorders in women consist of hormone replacement therapy, which have negative side effects that impact health, spurring the need to understand new mechanisms to employ new therapeutic strategies. Bidirectional communication between sensory neurons and the organs they innervate is an emerging area of interest in tissue physiology with a relevance in reproductive disorders. We hypothesized that the metabolic activity of sensory neurons has a profound effect on reproductive phenotypes. To investigate this phenomenon, we utilized a murine model with conditional deletion of liver kinase B1 (LKB1), a serine/threonine kinase that regulates cellular metabolism in sensory neurons (Nav1.8cre; LKB1fl/fl). LKB1 deletion in sensory neurons resulted in reduced ovarian innervation from dorsal root ganglia neurons and increased follicular turnover compared to littermate controls. Female mice with this LKB1 deletion had significantly more pups per litter compared to wild-type females. Interestingly, the LKB1 genotype of male breeders had no effect on fertility outcomes, thus indicating a female-specific role of sensory neuron metabolism in fertility. In summary, LKB1 expression in peripheral sensory neurons plays an important role in modulating fertility of female mice via ovarian sensory innervation.https://doi.org/10.1038/s41598-024-79947-2FertilitySensory neuronNav1.8LKB1Female
spellingShingle Melissa E Lenert
Emily K Debner
Michael D Burton
Sensory neuron LKB1 mediates ovarian and reproductive function
Scientific Reports
Fertility
Sensory neuron
Nav1.8
LKB1
Female
title Sensory neuron LKB1 mediates ovarian and reproductive function
title_full Sensory neuron LKB1 mediates ovarian and reproductive function
title_fullStr Sensory neuron LKB1 mediates ovarian and reproductive function
title_full_unstemmed Sensory neuron LKB1 mediates ovarian and reproductive function
title_short Sensory neuron LKB1 mediates ovarian and reproductive function
title_sort sensory neuron lkb1 mediates ovarian and reproductive function
topic Fertility
Sensory neuron
Nav1.8
LKB1
Female
url https://doi.org/10.1038/s41598-024-79947-2
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AT emilykdebner sensoryneuronlkb1mediatesovarianandreproductivefunction
AT michaeldburton sensoryneuronlkb1mediatesovarianandreproductivefunction