Activin A determines steroid levels and composition in the fetal testis.

Activin A determines steroid levels and composition in the fetal testis.
Endocrinology. 2020 Apr 10;:
Authors: Whiley PAF, O'Donnell L, Moody SC, Handelsman DJ, Young JC, Richards EA, Almstrup K, Western PS, Loveland KL
Abstract
Activin A promotes fetal mouse testis development, including by driving Sertoli cell proliferation and cord morphogenesis, but its mechanisms of action are undefined. We performed RNA-seq on testicular somatic cells from fetal activin A-deficient mice (Inhba KO) and wildtype littermates at embryonic ages 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 demonstrates for the first time that activin A acts on Sertoli cells to determine local steroid production during fetal testis deve...

Source: Endocrinology - April 9, 2020 Category: Endocrinology Authors: Whiley PAF, O'Donnell L, Moody SC, Handelsman DJ, Young JC, Richards EA, Almstrup K, Western PS, Loveland KL Tags: Endocrinology Source Type: research