Absence of Sirtuin 1 impairs the testicular development in cattleyak by inactivating SF‐1

Abstract

Cattleyak, which are interspecific hybrids between cattle and yak, display much higher growth performances than yak. However, F1 male cattleyak are infertile due to defective testicular development. Sirtuin 1 (SIRT1) is a histone deacetylase that is essential for various biological processes, while the roles of testicular SIRT1 in yak and cattleyak are still poorly understood. Here, we found that SIRT1 was localized in various kinds of yak testicular cells except elongated spermatids while it was deficient in cattleyak testis. Further studies indicated that cattleyak testis exhibited decreased histone acetylation levels on H3 and H4. One of SIRT1 co‐factors, steroidogenic factor‐1 (SF‐1), was lost in cattleyak testis at protein level. Expressions of several SF‐1 target genes responsible for Sertoli cell development and steroidogenesis, including STAR, CYP11A1, CYP26B1, FDX1 and HSD3B, decreased significantly in cattleyak testis. In addition, SIRT1‐mediated P53 acetylation was not responsible for the cell apoptosis in cattleyak testis. Taken together, our results suggested the deficiency of SIRT1 in yak testis caused inactivation of SF‐1 and the impairment of testicular development. This research provides theoretical bases for understanding the mechanism of cattleyak sterility and gives new insights in revealing the roles of SIRT1 in regulating yak testicular development.

Aberrant levels of DNA methylation and H3K9 acetylation in the testicular cells of crossbred cattle–yak showing infertility

“…Our study findings also suggest that the genes related to spermatogenesis are activated in the spermatogonia of mature 2-and 3-year-old yak by increasing AcK9 expression (compared to the modifications in the testicular cell assessment of cattle-yak compared to same-aged yak (Yin et al, 2020). Other acetylated histone modification levels at each stage of spermatogenic cells should be examined in the future.…”

“…On the other hand, the lower levels of AcK9 expression might repress the transcription of the genes in the spermatogonia of cattle–yak, that is repress spermatogonia differentiation, similar to immature yak. AcK9 showed the most decreased expression levels among the acetylated histone modifications in the testicular cell assessment of cattle–yak compared to same‐aged yak (Yin et al., 2020). Other acetylated histone modification levels at each stage of spermatogenic cells should be examined in the future.…”

“…During spermatogenesis, histones are highly acetylated to open and transcribe euchromatic domains and relax chromatin before their transient replacement by transition proteins (Gaucher et al., 2010; Qian et al., 2013). Compared to yak testicular tissues, cattle–yak testicular tissues show decreased levels of acetylated histones H3 and H4 (Yin et al., 2020); however, no information is available regarding these levels in each testicular cell type. Changes in the pattern of DNA methylation are known to be associated with male germ cell development and fertility maintenance, such as the gain or loss of methylation during the sperm developmental stage (Oakes et al., 2007; Trasler, 2009).…”

Cordycepin, a major bioactive component ofCordyceps militaris, ameliorates diabetes‐induced testicular damage through the Sirt1/Foxo3a pathway

“…Noteworthy, Sirt1‐knockout animals are infertile (Gorga et al, 2018). Also, the deficiency of SIRT1 in yak testis caused the impairment of testicular development (Yin et al, 2020). On the one hand, SIRT1 plays a vital role in regulating male reproduction, and on the other hand, activation of SIRT1 can exert antioxidant effects.…”

Studies on male gonadal toxicity of bisphenol A in diabetic rats: An example of exacerbation effect

“…SIRT1, a NAD‐dependent histone deacetylase essential for several biological processes in the testis of yak, and the absence of SIRT1 impaired the cattle yak, testicular development by inactivating steroidogenic factor‐1. [ 76 ] Chronic exposure of BPA at a low dose affects the spermatogenesis process through the modulation of SIRT1, with the consequences of apoptosis, oxidative stress, metabolism, and energy homeostasis. [ 15 ] BPA perturbed the SIRT1 gene expression mediated by ER signaling, which was further confirmed by using ER receptor antagonist fulvestrant in human ovarian cancer cell lines.…”