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Age-related changes in human Leydig cell status

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Harvard

Mularoni, V, Esposito, V, Di Persio, S, Vicini, E, Spadetta, G, Berloco, P, Fanelli, F, Mezzullo, M, Pagotto, U, Pelusi, C, Nielsen, JE, Rajpert-De Meyts, E, Jorgensen, N, Jorgensen, A & Boitani, C 2020, 'Age-related changes in human Leydig cell status' Human reproduction (Oxford, England), bind 35, nr. 12, s. 2663-2676. https://doi.org/10.1093/humrep/deaa271

APA

Mularoni, V., Esposito, V., Di Persio, S., Vicini, E., Spadetta, G., Berloco, P., ... Boitani, C. (2020). Age-related changes in human Leydig cell status. Human reproduction (Oxford, England), 35(12), 2663-2676. https://doi.org/10.1093/humrep/deaa271

CBE

Mularoni V, Esposito V, Di Persio S, Vicini E, Spadetta G, Berloco P, Fanelli F, Mezzullo M, Pagotto U, Pelusi C, Nielsen JE, Rajpert-De Meyts E, Jorgensen N, Jorgensen A, Boitani C. 2020. Age-related changes in human Leydig cell status. Human reproduction (Oxford, England). 35(12):2663-2676. https://doi.org/10.1093/humrep/deaa271

MLA

Vancouver

Mularoni V, Esposito V, Di Persio S, Vicini E, Spadetta G, Berloco P o.a. Age-related changes in human Leydig cell status. Human reproduction (Oxford, England). 2020 dec 1;35(12):2663-2676. https://doi.org/10.1093/humrep/deaa271

Author

Mularoni, Valentina ; Esposito, Valentina ; Di Persio, Sara ; Vicini, Elena ; Spadetta, Gustavo ; Berloco, Pasquale ; Fanelli, Flaminia ; Mezzullo, Marco ; Pagotto, Uberto ; Pelusi, Carla ; Nielsen, John E ; Rajpert-De Meyts, Ewa ; Jorgensen, Niels ; Jorgensen, Anne ; Boitani, Carla. / Age-related changes in human Leydig cell status. I: Human reproduction (Oxford, England). 2020 ; Bind 35, Nr. 12. s. 2663-2676.

Bibtex

@article{9e832b07a9d14e2bb57710876e8e1c6f,
title = "Age-related changes in human Leydig cell status",
abstract = "STUDY QUESTION: What are the consequences of ageing on human Leydig cell number and hormonal function?SUMMARY ANSWER: Leydig cell number significantly decreases in parallel with INSL3 expression and Sertoli cell number in aged men, yet the in vitro Leydig cell androgenic potential does not appear to be compromised by advancing age.WHAT IS KNOWN ALREADY: There is extensive evidence that ageing is accompanied by decline in serum testosterone levels, a general involution of testis morphology and reduced spermatogenic function. A few studies have previously addressed single features of the human aged testis phenotype one at a time, but mostly in tissue from patients with prostate cancer.STUDY DESIGN, SIZE, DURATION: This comprehensive study examined testis morphology, Leydig cell and Sertoli cell number, steroidogenic enzyme expression, INSL3 expression and androgen secretion by testicular fragments in vitro. The majority of these endpoints were concomitantly evaluated in the same individuals that all displayed complete spermatogenesis.PARTICIPANTS/MATERIALS, SETTING, METHODS: Testis biopsies were obtained from 15 heart beating organ donors (age range: 19-85 years) and 24 patients (age range: 19-45 years) with complete spermatogenesis. Leydig cells and Sertoli cells were counted following identification by immunohistochemical staining of specific cell markers. Gene expression analysis of INSL3 and steroidogenic enzymes was carried out by qRT-PCR. Secretion of 17-OH-progesterone, dehydroepiandrosterone, androstenedione and testosterone by in vitro cultured testis fragments was measured by LC-MS/MS. All endpoints were analysed in relation to age.MAIN RESULTS AND THE ROLE OF CHANCE: Increasing age was negatively associated with Leydig cell number (R = -0.49; P < 0.01) and concomitantly with the Sertoli cell population size (R= -0.55; P < 0.001). A positive correlation (R = 0.57; P < 0.001) between Sertoli cell and Leydig cell numbers was detected at all ages, indicating that somatic cell attrition is a relevant cellular manifestation of human testis status during ageing. INSL3 mRNA expression (R= -0.52; P < 0.05) changed in parallel with Leydig cell number and age. Importantly, steroidogenic capacity of Leydig cells in cultured testis tissue fragments from young and old donors did not differ. Consistently, age did not influence the mRNA expression of steroidogenic enzymes. The described changes in Leydig cell phenotype with ageing are strengthened by the fact that the different age-related effects were mostly evaluated in tissue from the same men.LIMITATIONS, REASONS FOR CAUTION: In vitro androgen production analysis could not be correlated with in vivo hormone values of the organ donors. In addition, the number of samples was relatively small and there was scarce information about the concomitant presence of potential confounding variables.WIDER IMPLICATIONS OF THE FINDINGS: This study provides a novel insight into the effects of ageing on human Leydig cell status. The correlation between Leydig cell number and Sertoli cell number at any age implies a connection between these two cell types, which may be of particular relevance in understanding male reproductive disorders in the elderly. However aged Leydig cells do not lose their in vitro ability to produce androgens. Our data have implications in the understanding of the physiological role and regulation of intratesticular sex steroid levels during the complex process of ageing in humans.STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from Prin 2010 and 2017. The authors have no conflicts of interest.TRIAL REGISTRATION NUMBER: N/A.",
author = "Valentina Mularoni and Valentina Esposito and {Di Persio}, Sara and Elena Vicini and Gustavo Spadetta and Pasquale Berloco and Flaminia Fanelli and Marco Mezzullo and Uberto Pagotto and Carla Pelusi and Nielsen, {John E} and {Rajpert-De Meyts}, Ewa and Niels Jorgensen and Anne Jorgensen and Carla Boitani",
note = "{\circledC} The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.",
year = "2020",
month = "12",
day = "1",
doi = "10.1093/humrep/deaa271",
language = "English",
volume = "35",
pages = "2663--2676",
journal = "Human Reproduction",
issn = "0268-1161",
publisher = "Oxford University Press",
number = "12",

}

RIS

TY - JOUR

T1 - Age-related changes in human Leydig cell status

AU - Mularoni, Valentina

AU - Esposito, Valentina

AU - Di Persio, Sara

AU - Vicini, Elena

AU - Spadetta, Gustavo

AU - Berloco, Pasquale

AU - Fanelli, Flaminia

AU - Mezzullo, Marco

AU - Pagotto, Uberto

AU - Pelusi, Carla

AU - Nielsen, John E

AU - Rajpert-De Meyts, Ewa

AU - Jorgensen, Niels

AU - Jorgensen, Anne

AU - Boitani, Carla

N1 - © The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - STUDY QUESTION: What are the consequences of ageing on human Leydig cell number and hormonal function?SUMMARY ANSWER: Leydig cell number significantly decreases in parallel with INSL3 expression and Sertoli cell number in aged men, yet the in vitro Leydig cell androgenic potential does not appear to be compromised by advancing age.WHAT IS KNOWN ALREADY: There is extensive evidence that ageing is accompanied by decline in serum testosterone levels, a general involution of testis morphology and reduced spermatogenic function. A few studies have previously addressed single features of the human aged testis phenotype one at a time, but mostly in tissue from patients with prostate cancer.STUDY DESIGN, SIZE, DURATION: This comprehensive study examined testis morphology, Leydig cell and Sertoli cell number, steroidogenic enzyme expression, INSL3 expression and androgen secretion by testicular fragments in vitro. The majority of these endpoints were concomitantly evaluated in the same individuals that all displayed complete spermatogenesis.PARTICIPANTS/MATERIALS, SETTING, METHODS: Testis biopsies were obtained from 15 heart beating organ donors (age range: 19-85 years) and 24 patients (age range: 19-45 years) with complete spermatogenesis. Leydig cells and Sertoli cells were counted following identification by immunohistochemical staining of specific cell markers. Gene expression analysis of INSL3 and steroidogenic enzymes was carried out by qRT-PCR. Secretion of 17-OH-progesterone, dehydroepiandrosterone, androstenedione and testosterone by in vitro cultured testis fragments was measured by LC-MS/MS. All endpoints were analysed in relation to age.MAIN RESULTS AND THE ROLE OF CHANCE: Increasing age was negatively associated with Leydig cell number (R = -0.49; P < 0.01) and concomitantly with the Sertoli cell population size (R= -0.55; P < 0.001). A positive correlation (R = 0.57; P < 0.001) between Sertoli cell and Leydig cell numbers was detected at all ages, indicating that somatic cell attrition is a relevant cellular manifestation of human testis status during ageing. INSL3 mRNA expression (R= -0.52; P < 0.05) changed in parallel with Leydig cell number and age. Importantly, steroidogenic capacity of Leydig cells in cultured testis tissue fragments from young and old donors did not differ. Consistently, age did not influence the mRNA expression of steroidogenic enzymes. The described changes in Leydig cell phenotype with ageing are strengthened by the fact that the different age-related effects were mostly evaluated in tissue from the same men.LIMITATIONS, REASONS FOR CAUTION: In vitro androgen production analysis could not be correlated with in vivo hormone values of the organ donors. In addition, the number of samples was relatively small and there was scarce information about the concomitant presence of potential confounding variables.WIDER IMPLICATIONS OF THE FINDINGS: This study provides a novel insight into the effects of ageing on human Leydig cell status. The correlation between Leydig cell number and Sertoli cell number at any age implies a connection between these two cell types, which may be of particular relevance in understanding male reproductive disorders in the elderly. However aged Leydig cells do not lose their in vitro ability to produce androgens. Our data have implications in the understanding of the physiological role and regulation of intratesticular sex steroid levels during the complex process of ageing in humans.STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from Prin 2010 and 2017. The authors have no conflicts of interest.TRIAL REGISTRATION NUMBER: N/A.

AB - STUDY QUESTION: What are the consequences of ageing on human Leydig cell number and hormonal function?SUMMARY ANSWER: Leydig cell number significantly decreases in parallel with INSL3 expression and Sertoli cell number in aged men, yet the in vitro Leydig cell androgenic potential does not appear to be compromised by advancing age.WHAT IS KNOWN ALREADY: There is extensive evidence that ageing is accompanied by decline in serum testosterone levels, a general involution of testis morphology and reduced spermatogenic function. A few studies have previously addressed single features of the human aged testis phenotype one at a time, but mostly in tissue from patients with prostate cancer.STUDY DESIGN, SIZE, DURATION: This comprehensive study examined testis morphology, Leydig cell and Sertoli cell number, steroidogenic enzyme expression, INSL3 expression and androgen secretion by testicular fragments in vitro. The majority of these endpoints were concomitantly evaluated in the same individuals that all displayed complete spermatogenesis.PARTICIPANTS/MATERIALS, SETTING, METHODS: Testis biopsies were obtained from 15 heart beating organ donors (age range: 19-85 years) and 24 patients (age range: 19-45 years) with complete spermatogenesis. Leydig cells and Sertoli cells were counted following identification by immunohistochemical staining of specific cell markers. Gene expression analysis of INSL3 and steroidogenic enzymes was carried out by qRT-PCR. Secretion of 17-OH-progesterone, dehydroepiandrosterone, androstenedione and testosterone by in vitro cultured testis fragments was measured by LC-MS/MS. All endpoints were analysed in relation to age.MAIN RESULTS AND THE ROLE OF CHANCE: Increasing age was negatively associated with Leydig cell number (R = -0.49; P < 0.01) and concomitantly with the Sertoli cell population size (R= -0.55; P < 0.001). A positive correlation (R = 0.57; P < 0.001) between Sertoli cell and Leydig cell numbers was detected at all ages, indicating that somatic cell attrition is a relevant cellular manifestation of human testis status during ageing. INSL3 mRNA expression (R= -0.52; P < 0.05) changed in parallel with Leydig cell number and age. Importantly, steroidogenic capacity of Leydig cells in cultured testis tissue fragments from young and old donors did not differ. Consistently, age did not influence the mRNA expression of steroidogenic enzymes. The described changes in Leydig cell phenotype with ageing are strengthened by the fact that the different age-related effects were mostly evaluated in tissue from the same men.LIMITATIONS, REASONS FOR CAUTION: In vitro androgen production analysis could not be correlated with in vivo hormone values of the organ donors. In addition, the number of samples was relatively small and there was scarce information about the concomitant presence of potential confounding variables.WIDER IMPLICATIONS OF THE FINDINGS: This study provides a novel insight into the effects of ageing on human Leydig cell status. The correlation between Leydig cell number and Sertoli cell number at any age implies a connection between these two cell types, which may be of particular relevance in understanding male reproductive disorders in the elderly. However aged Leydig cells do not lose their in vitro ability to produce androgens. Our data have implications in the understanding of the physiological role and regulation of intratesticular sex steroid levels during the complex process of ageing in humans.STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from Prin 2010 and 2017. The authors have no conflicts of interest.TRIAL REGISTRATION NUMBER: N/A.

U2 - 10.1093/humrep/deaa271

DO - 10.1093/humrep/deaa271

M3 - Journal article

VL - 35

SP - 2663

EP - 2676

JO - Human Reproduction

JF - Human Reproduction

SN - 0268-1161

IS - 12

ER -

ID: 61115900