Activin A Determines Steroid Levels and Composition in the Fetal Testis
| Autor: | Kate L Loveland, Sarah C Moody, Julia C. Young, Patrick S Western, David J. Handelsman, Elizabeth A. Richards, Kristian Almstrup, Liza O'Donnell, Penny A. F. Whiley |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine endocrine system medicine.medical_specialty animal structures Somatic cell Sertoli cell proliferation Biology Mice 03 medical and health sciences 0302 clinical medicine Endocrinology Pregnancy Internal medicine Lipid droplet Testis medicine Animals Gonadal Steroid Hormones Testosterone Mice Knockout Fetus Sex Determination Processes Sertoli cell Activins 030104 developmental biology medicine.anatomical_structure embryonic structures Female INHBA Gene Spermatogenesis 030217 neurology & neurosurgery |
| Zdroj: | Endocrinology. 161 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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