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Effects of aging and macrophages on mice stem Leydig cell proliferation and differentiation in vitro

BACKGROUND: Testosterone plays a critical role in maintaining reproductive functions and well-beings of the males. Adult testicular Leydig cells (LCs) produce testosterone and are generated from stem Leydig cells (SLCs) during puberty through adulthood. In addition, macrophages are critical in the S...

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Autores principales: Shao, Jingjing, Wang, Jiexia, Wen, Xin, Xie, Jiajia, Huang, Fu, Guan, Xiaoju, Hao, Xinrui, Duan, Ping, Chen, Congde, Chen, Haolin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10083278/
https://www.ncbi.nlm.nih.gov/pubmed/37051204
http://dx.doi.org/10.3389/fendo.2023.1139281
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author Shao, Jingjing
Wang, Jiexia
Wen, Xin
Xie, Jiajia
Huang, Fu
Guan, Xiaoju
Hao, Xinrui
Duan, Ping
Chen, Congde
Chen, Haolin
author_facet Shao, Jingjing
Wang, Jiexia
Wen, Xin
Xie, Jiajia
Huang, Fu
Guan, Xiaoju
Hao, Xinrui
Duan, Ping
Chen, Congde
Chen, Haolin
author_sort Shao, Jingjing
collection PubMed
description BACKGROUND: Testosterone plays a critical role in maintaining reproductive functions and well-beings of the males. Adult testicular Leydig cells (LCs) produce testosterone and are generated from stem Leydig cells (SLCs) during puberty through adulthood. In addition, macrophages are critical in the SLC regulatory niche for normal testicular function. Age-related reduction in serum testosterone contributes to a number of metabolic and quality-of-life changes in males, as well as age-related changes in immunological functions. How aging and testicular macrophages may affect SLC function is still unclear. METHODS: SLCs and macrophages were purified from adult and aged mice via FACS using CD51 as a marker protein. The sorted cells were first characterized and then co-cultured in vitro to examine how aging and macrophages may affect SLC proliferation and differentiation. To elucidate specific aging effects on both cell types, co-culture of sorted SLCs and macrophages were also carried out across two ages. RESULTS: CD51+ (weakly positive) and CD51++ (strongly positive) cells expressed typical SLC and macrophage markers, respectively. However, with aging, both cell types increased expression of multiple cytokine genes, such as IL-1b, IL-6 and IL-8. Moreover, old CD51+ SLCs reduced their proliferation and differentiation, with a more significant reduction in differentiation (2X) than proliferation (30%). Age matched CD51++ macrophages inhibited CD51+ SLC development, with a more significant reduction in old cells (60%) than young (40%). Crossed-age co-culture experiments indicated that the age of CD51+ SLCs plays a more significant role in determining age-related inhibitory effects. In LC lineage formation, CD51+ SLC had both reduced LC lineage markers and increased myoid cell lineage markers, suggesting an age-related lineage shift for SLCs. CONCLUSION: The results suggest that aging affected both SLC function and their regulatory niche cell, macrophages.
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spelling pubmed-100832782023-04-11 Effects of aging and macrophages on mice stem Leydig cell proliferation and differentiation in vitro Shao, Jingjing Wang, Jiexia Wen, Xin Xie, Jiajia Huang, Fu Guan, Xiaoju Hao, Xinrui Duan, Ping Chen, Congde Chen, Haolin Front Endocrinol (Lausanne) Endocrinology BACKGROUND: Testosterone plays a critical role in maintaining reproductive functions and well-beings of the males. Adult testicular Leydig cells (LCs) produce testosterone and are generated from stem Leydig cells (SLCs) during puberty through adulthood. In addition, macrophages are critical in the SLC regulatory niche for normal testicular function. Age-related reduction in serum testosterone contributes to a number of metabolic and quality-of-life changes in males, as well as age-related changes in immunological functions. How aging and testicular macrophages may affect SLC function is still unclear. METHODS: SLCs and macrophages were purified from adult and aged mice via FACS using CD51 as a marker protein. The sorted cells were first characterized and then co-cultured in vitro to examine how aging and macrophages may affect SLC proliferation and differentiation. To elucidate specific aging effects on both cell types, co-culture of sorted SLCs and macrophages were also carried out across two ages. RESULTS: CD51+ (weakly positive) and CD51++ (strongly positive) cells expressed typical SLC and macrophage markers, respectively. However, with aging, both cell types increased expression of multiple cytokine genes, such as IL-1b, IL-6 and IL-8. Moreover, old CD51+ SLCs reduced their proliferation and differentiation, with a more significant reduction in differentiation (2X) than proliferation (30%). Age matched CD51++ macrophages inhibited CD51+ SLC development, with a more significant reduction in old cells (60%) than young (40%). Crossed-age co-culture experiments indicated that the age of CD51+ SLCs plays a more significant role in determining age-related inhibitory effects. In LC lineage formation, CD51+ SLC had both reduced LC lineage markers and increased myoid cell lineage markers, suggesting an age-related lineage shift for SLCs. CONCLUSION: The results suggest that aging affected both SLC function and their regulatory niche cell, macrophages. Frontiers Media S.A. 2023-03-27 /pmc/articles/PMC10083278/ /pubmed/37051204 http://dx.doi.org/10.3389/fendo.2023.1139281 Text en Copyright © 2023 Shao, Wang, Wen, Xie, Huang, Guan, Hao, Duan, Chen and Chen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Shao, Jingjing
Wang, Jiexia
Wen, Xin
Xie, Jiajia
Huang, Fu
Guan, Xiaoju
Hao, Xinrui
Duan, Ping
Chen, Congde
Chen, Haolin
Effects of aging and macrophages on mice stem Leydig cell proliferation and differentiation in vitro
title Effects of aging and macrophages on mice stem Leydig cell proliferation and differentiation in vitro
title_full Effects of aging and macrophages on mice stem Leydig cell proliferation and differentiation in vitro
title_fullStr Effects of aging and macrophages on mice stem Leydig cell proliferation and differentiation in vitro
title_full_unstemmed Effects of aging and macrophages on mice stem Leydig cell proliferation and differentiation in vitro
title_short Effects of aging and macrophages on mice stem Leydig cell proliferation and differentiation in vitro
title_sort effects of aging and macrophages on mice stem leydig cell proliferation and differentiation in vitro
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10083278/
https://www.ncbi.nlm.nih.gov/pubmed/37051204
http://dx.doi.org/10.3389/fendo.2023.1139281
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