Identification of Sertoli cell-specific transcripts in the mouse testis and the role of FSH and androgen in the control of Sertoli cell activity

Abstract

BackgroundThe Sertoli cells act to induce testis differentiation and subsequent development in fetal and post-natal life which makes them key to an understanding of testis biology. As a major step towards characterisation of factors involved in Sertoli cell function we have identified Sertoli cell-specific transcripts in the mouse testis and have used the data to identify Sertoli cell-specific transcripts altered in mice lacking follicle-stimulating hormone receptors (FSHRKO) and/or androgen receptors (AR) in the Sertoli cells (SCARKO).ResultsAdult iDTR mice were injected with busulfan to ablate the germ cells and 50 days later they were treated with diphtheria toxin (DTX) to ablate the Sertoli cells. RNAseq carried out on testes from control, busulfan-treated and busulfan + DTX-treated mice identified 701 Sertoli-specific transcripts and 4302 germ cell-specific transcripts. This data was mapped against results from microarrays using testicular mRNA from 20 day-old FSHRKO, SCARKO and FSHRKO.SCARKO mice. Results show that of the 534 Sertoli cell-specific transcripts present on the gene chips, 85% were altered in the FSHRKO mice and 94% in the SCARKO mice (mostly reduced in both cases). In the FSHRKO.SCARKO mice additive or synergistic effects were seen for most transcripts. Age-dependent studies on a selected number of Sertoli cell-specific transcripts, showed that the marked effects in the FSHRKO at 20 days had largely disappeared by adulthood although synergistic effects of FSHR and AR knockout were seen.ConclusionsThese studies have identified the Sertoli cell-specific transcriptome in the mouse testis and have shown that most genes in the transcriptome are FSH- and androgen-dependent at puberty although the importance of FSH diminishes towards adulthood.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4357-3) contains supplementary material, which is available to authorized users.

Characterization of rodent Sertoli cell primary cultures

“…This raises the possibility that testicular endothelial cells and fibroblasts might also express WT1 and FSHr. In addition, Soffientini et al (2017) showed that the ablation of Sertoli cells does not extinguish Wt1 transcripts in the testis, confirming that some of the markers currently accepted as Sertoli cell-specific are also expressed by other testicular cells types (Soffientini et al, 2017); thus limiting their use to characterize Sertoli cells.…”

“…Sertoli cells exhibited some enriched transcripts with high levels of expression between birth and PND 6, and others rising at PND 8, peaking between PND 10 and 14, and returning to basal levels after 14-18 days (Shima et al, 2004). In fact, none of the Sertoli-specific transcripts were present in a steady-state over time, Although a number of studies were performed to identify new Sertoli cell markers, there is little agreement between the findings (De Gendt, Verhoeven, Amieux, & Wilkinson, 2014;Green et al, 2018;Sanz et al, 2013;Soffientini et al, 2017;Zimmermann et al, 2015). Interestingly, from hundreds of identified transcripts, only 42 (5-12%) appeared consistently in all these studies (Table 2), and some of the transcripts considered specific for Sertoli cells by the authors, such as Amh, Sox9, Rhox5, and Gdnf, were excluded from the selection.…”

Mapping molecular pathways for embryonic Sertoli cells derivation based on differentiation model of mouse embryonic stem cells

“…Results showed a differentiation process from mESCs to eSLCs was established mimetic to the presumptive developmental process in embryos. Furthermore, the induced eSLCs had similar characteristic and expression of specific markers with eSCs including, AMH + , FSHR + , GDNF + , FASL + , and EMX2 − [1,41,42]. Moreover, through the inducing approach, there were ring-like structures and tubular-like structures formed as the same behavior as those eSCs in embryos [6,43].…”

Role of Follicle-Stimulating Hormone in Spermatogenesis

“…The general phenomenon is that FSH mostly elevates the expression of a large number of Sertoli cell genes (55–57). In neonatal life, Sertoli cells proliferate extensively, and logically mainly the transcripts of genes involved in DNA replication, cell cycle and stem cell factors are enriched (54).…”

“…FSH also regulates the expression of genes involved in fatty acid metabolism and mitochondrial biogenesis, which is vital for the energy metabolism of seminiferous tubules (71). Another example of FSH-induced actions of Sertoli cells on germ cells is Aqp8 , one of the most altered genes in the absence of FSH action (57). Aqp8 is involved in water transport through membranes (72) and is strongly down-regulated in Fshr -KO mice (57).…”