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Activin A determines steroid levels and composition in the fetal testis

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Harvard

Whiley, PAF, O'Donnell, L, Moody, SC, Handelsman, DJ, Young, JC, Richards, EA, Almstrup, K, Western, PS & Loveland, KL 2020, 'Activin A determines steroid levels and composition in the fetal testis', Endocrinology, bind 161, nr. 7, bqaa058, s. 1-16. https://doi.org/10.1210/endocr/bqaa058

APA

Whiley, P. A. F., O'Donnell, L., Moody, S. C., Handelsman, D. J., Young, J. C., Richards, E. A., Almstrup, K., Western, P. S., & Loveland, K. L. (2020). Activin A determines steroid levels and composition in the fetal testis. Endocrinology, 161(7), 1-16. [bqaa058]. https://doi.org/10.1210/endocr/bqaa058

CBE

Whiley PAF, O'Donnell L, Moody SC, Handelsman DJ, Young JC, Richards EA, Almstrup K, Western PS, Loveland KL. 2020. Activin A determines steroid levels and composition in the fetal testis. Endocrinology. 161(7):1-16. https://doi.org/10.1210/endocr/bqaa058

MLA

Vancouver

Whiley PAF, O'Donnell L, Moody SC, Handelsman DJ, Young JC, Richards EA o.a. Activin A determines steroid levels and composition in the fetal testis. Endocrinology. 2020 jul 1;161(7):1-16. bqaa058. https://doi.org/10.1210/endocr/bqaa058

Author

Whiley, Penny A F ; O'Donnell, Liza ; Moody, Sarah C ; Handelsman, David J ; Young, Julia C ; Richards, Elizabeth A ; Almstrup, Kristian ; Western, Patrick S ; Loveland, Kate L. / Activin A determines steroid levels and composition in the fetal testis. I: Endocrinology. 2020 ; Bind 161, Nr. 7. s. 1-16.

Bibtex

@article{181f7fdc875f4d819c5c46e9d2a2cbba,
title = "Activin A determines steroid levels and composition in the fetal testis",
abstract = "Activin A promotes fetal mouse testis development, including driving Sertoli cell proliferation and cord morphogenesis, but its mechanisms of action are undefined. We performed ribonucleic acid sequencing (RNA-seq) on testicular somatic cells from fetal activin A-deficient mice (Inhba KO) and wildtype littermates at embryonic day (E) E13.5 and E15.5. Analysis of whole gonads provided validation, and cultures with a pathway inhibitor discerned acute from chronic effects of altered activin A bioactivity. Activin A deficiency predominantly affects the Sertoli cell transcriptome. New candidate targets include Minar1, Sel1l3, Vnn1, Sfrp4, Masp1, Nell1, Tthy1 and Prss12. Importantly, the testosterone (T) biosynthetic enzymes present in fetal Sertoli cells, Hsd17b1 and Hsd17b3, were identified as activin-responsive. Activin-deficient testes contained elevated androstenedione (A4), displayed an Inhba gene dose-dependent A4/T ratio, and contained 11-keto androgens. The remarkable accumulation of lipid droplets in both Sertoli and germ cells at E15.5 indicated impaired lipid metabolism in the absence of activin A. This demonstrated for the first time that activin A acts on Sertoli cells to determine local steroid production during fetal testis development. These outcomes reveal how compounds that perturb fetal steroidogenesis can function through cell-specific mechanisms and can indicate how altered activin levels in utero may impact testis development.",
keywords = "11-ketotestosterone, Hsd17b1, Hsd17b3, spermatogenesis, steroidogenesis",
author = "Whiley, {Penny A F} and Liza O'Donnell and Moody, {Sarah C} and Handelsman, {David J} and Young, {Julia C} and Richards, {Elizabeth A} and Kristian Almstrup and Western, {Patrick S} and Loveland, {Kate L}",
note = "{\textcopyright} Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.",
year = "2020",
month = jul,
day = "1",
doi = "10.1210/endocr/bqaa058",
language = "English",
volume = "161",
pages = "1--16",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The/Endocrine Society",
number = "7",

}

RIS

TY - JOUR

T1 - Activin A determines steroid levels and composition in the fetal testis

AU - Whiley, Penny A F

AU - O'Donnell, Liza

AU - Moody, Sarah C

AU - Handelsman, David J

AU - Young, Julia C

AU - Richards, Elizabeth A

AU - Almstrup, Kristian

AU - Western, Patrick S

AU - Loveland, Kate L

N1 - © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2020/7/1

Y1 - 2020/7/1

N2 - Activin A promotes fetal mouse testis development, including driving Sertoli cell proliferation and cord morphogenesis, but its mechanisms of action are undefined. We performed ribonucleic acid sequencing (RNA-seq) on testicular somatic cells from fetal activin A-deficient mice (Inhba KO) and wildtype littermates at embryonic day (E) E13.5 and E15.5. Analysis of whole gonads provided validation, and cultures with a pathway inhibitor discerned acute from chronic effects of altered activin A bioactivity. Activin A deficiency predominantly affects the Sertoli cell transcriptome. New candidate targets include Minar1, Sel1l3, Vnn1, Sfrp4, Masp1, Nell1, Tthy1 and Prss12. Importantly, the testosterone (T) biosynthetic enzymes present in fetal Sertoli cells, Hsd17b1 and Hsd17b3, were identified as activin-responsive. Activin-deficient testes contained elevated androstenedione (A4), displayed an Inhba gene dose-dependent A4/T ratio, and contained 11-keto androgens. The remarkable accumulation of lipid droplets in both Sertoli and germ cells at E15.5 indicated impaired lipid metabolism in the absence of activin A. This demonstrated for the first time that activin A acts on Sertoli cells to determine local steroid production during fetal testis development. These outcomes reveal how compounds that perturb fetal steroidogenesis can function through cell-specific mechanisms and can indicate how altered activin levels in utero may impact testis development.

AB - Activin A promotes fetal mouse testis development, including driving Sertoli cell proliferation and cord morphogenesis, but its mechanisms of action are undefined. We performed ribonucleic acid sequencing (RNA-seq) on testicular somatic cells from fetal activin A-deficient mice (Inhba KO) and wildtype littermates at embryonic day (E) E13.5 and E15.5. Analysis of whole gonads provided validation, and cultures with a pathway inhibitor discerned acute from chronic effects of altered activin A bioactivity. Activin A deficiency predominantly affects the Sertoli cell transcriptome. New candidate targets include Minar1, Sel1l3, Vnn1, Sfrp4, Masp1, Nell1, Tthy1 and Prss12. Importantly, the testosterone (T) biosynthetic enzymes present in fetal Sertoli cells, Hsd17b1 and Hsd17b3, were identified as activin-responsive. Activin-deficient testes contained elevated androstenedione (A4), displayed an Inhba gene dose-dependent A4/T ratio, and contained 11-keto androgens. The remarkable accumulation of lipid droplets in both Sertoli and germ cells at E15.5 indicated impaired lipid metabolism in the absence of activin A. This demonstrated for the first time that activin A acts on Sertoli cells to determine local steroid production during fetal testis development. These outcomes reveal how compounds that perturb fetal steroidogenesis can function through cell-specific mechanisms and can indicate how altered activin levels in utero may impact testis development.

KW - 11-ketotestosterone

KW - Hsd17b1

KW - Hsd17b3

KW - spermatogenesis

KW - steroidogenesis

UR - http://www.scopus.com/inward/record.url?scp=85086355903&partnerID=8YFLogxK

U2 - 10.1210/endocr/bqaa058

DO - 10.1210/endocr/bqaa058

M3 - Journal article

C2 - 32274496

VL - 161

SP - 1

EP - 16

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 7

M1 - bqaa058

ER -

ID: 59983970