Specific Transcriptomic Signatures and Dual Regulation of Steroidogenesis Between Fetal and Adult Mouse Leydig Cells

Pauline Sararols; Isabelle Stévant; Yasmine Neirijnck; Diane Rebourcet; Annalucia Darbey; Michael K. Curley; Françoise Kühne; Emmanouil Dermitzakis; Lee B. Smith; Serge Nef

doi:10.3389/fcell.2021.695546

Specific Transcriptomic Signatures and Dual Regulation of Steroidogenesis Between Fetal and Adult Mouse Leydig Cells

Pauline Sararols, Isabelle Stévant, Yasmine Neirijnck, Diane Rebourcet, Annalucia Darbey, Michael K. Curley, Françoise Kühne, Emmanouil Dermitzakis, Lee B. Smith, Serge Nef

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

Leydig cells (LC) are the main testicular androgen-producing cells. In eutherian mammals, two types of LCs emerge successively during testicular development, fetal Leydig cells (FLCs) and adult Leydig cells (ALCs). Both display significant differences in androgen production and regulation. Using bulk RNA sequencing, we compared the transcriptomes of both LC populations to characterize their specific transcriptional and functional features. Despite similar transcriptomic profiles, a quarter of the genes show significant variations in expression between FLCs and ALCs. Non-transcriptional events, such as alternative splicing was also observed, including a high rate of intron retention in FLCs compared to ALCs. The use of single-cell RNA sequencing data also allowed the identification of nine FLC-specific genes and 50 ALC-specific genes. Expression of the corticotropin-releasing hormone 1 (Crhr1) receptor and the ACTH receptor melanocortin type 2 receptor (Mc2r) specifically in FLCs suggests a dual regulation of steroidogenesis. The androstenedione synthesis by FLCs is stimulated by luteinizing hormone (LH), corticotrophin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH) whereas the testosterone synthesis by ALCs is dependent exclusively on LH. Overall, our study provides a useful database to explore LC development and functions.

Original language	English
Article number	695546
Journal	Frontiers in Cell and Developmental Biology
Volume	9
DOIs	https://doi.org/10.3389/fcell.2021.695546
State	Published - 28 Jun 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© Copyright © 2021 Sararols, Stévant, Neirijnck, Rebourcet, Darbey, Curley, Kühne, Dermitzakis, Smith and Nef.

Funding

This work was supported by the Swiss National Science Foundation (Grant 31003A_173070 and 310030_200316/1 to SN); and the Département de l’Instruction Publique of the State of Geneva (to SN). Department of Health, National Health and Medical Research Council (NHMRC), Grant/Award Number: APP1158344 (to LS and DR). The authors thank Violaine Regard from the NEF Laboratory, C?cile Gameiro, and Gregory Schneiter from the Flow Cytometry Facility, the Genomics Platform of iGE3, and the Animal Facility of the Faculty of Medicine of the University of Geneva. Funding. This work was supported by the Swiss National Science Foundation (Grant 31003A_173070 and 310030_200316/1 to SN); and the D?partement de l?Instruction Publique of the State of Geneva (to SN). Department of Health, National Health and Medical Research Council (NHMRC), Grant/Award Number: APP1158344 (to LS and DR).

Funders	Funder number
D?partement de l?Instruction Publique of the State of Geneva
Département de l’Instruction Publique of the State of Geneva
NEF Laboratory
Department of Health and Social Care
National Health and Medical Research Council	APP1158344
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung	31003A_173070, 310030_200316/1
Université de Genève

Keywords

RNA sequencing
adult Leydig cell
androgen
fetal Leydig cell
single cell RNA sequencing
testis

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10.3389/fcell.2021.695546

Cite this

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title = "Specific Transcriptomic Signatures and Dual Regulation of Steroidogenesis Between Fetal and Adult Mouse Leydig Cells",

abstract = "Leydig cells (LC) are the main testicular androgen-producing cells. In eutherian mammals, two types of LCs emerge successively during testicular development, fetal Leydig cells (FLCs) and adult Leydig cells (ALCs). Both display significant differences in androgen production and regulation. Using bulk RNA sequencing, we compared the transcriptomes of both LC populations to characterize their specific transcriptional and functional features. Despite similar transcriptomic profiles, a quarter of the genes show significant variations in expression between FLCs and ALCs. Non-transcriptional events, such as alternative splicing was also observed, including a high rate of intron retention in FLCs compared to ALCs. The use of single-cell RNA sequencing data also allowed the identification of nine FLC-specific genes and 50 ALC-specific genes. Expression of the corticotropin-releasing hormone 1 (Crhr1) receptor and the ACTH receptor melanocortin type 2 receptor (Mc2r) specifically in FLCs suggests a dual regulation of steroidogenesis. The androstenedione synthesis by FLCs is stimulated by luteinizing hormone (LH), corticotrophin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH) whereas the testosterone synthesis by ALCs is dependent exclusively on LH. Overall, our study provides a useful database to explore LC development and functions.",

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AU - Rebourcet, Diane

AU - Darbey, Annalucia

AU - Curley, Michael K.

AU - Kühne, Françoise

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AU - Nef, Serge

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Specific Transcriptomic Signatures and Dual Regulation of Steroidogenesis Between Fetal and Adult Mouse Leydig Cells

Abstract

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