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The transition from meiotic spermatocytes to postmeiotic haploid germ cells constitutes an essential step in spermatogenesis. The epigenomic regulatory mechanisms underlying this transition remain unclear. Here, we find a prominent transcriptomic switch from the late spermatocytes to the early round spermatids during the meiotic-to-postmeiotic transition, which is associated with robust histone acetylation changes across the genome. Among histone deacetylases (HDACs) and acetyltransferases, we find that HDAC3 is selectively expressed in the late meiotic and early haploid stages. Three independent mouse lines with the testis-specific knockout of HDAC3 show infertility and defects in meiotic exit with an arrest at the late stage of meiosis or early stage of round spermatids. Stage-specific RNA-seq and histone acetylation ChIP-seq analyses reveal that HDAC3 represses meiotic/spermatogonial genes and activates postmeiotic haploid gene programs during meiotic exit, with associated histone acetylation alterations. Unexpectedly, abolishing HDAC3 catalytic activity by missense mutations in the nuclear receptor corepressor (NCOR or SMRT) does not cause infertility, despite causing histone hyperacetylation as HDAC3 knockout, demonstrating that HDAC3 enzyme activity is not required for spermatogenesis. Motif analysis of the HDAC3 cistrome in the testes identified SOX30, which has a similar spatiotemporal expression pattern as HDAC3 during spermatogenesis. Depletion of SOX30 in the testes abolishes the genomic recruitment of the HDAC3 to the binding sites. Collectively, these results establish the SOX30/HDAC3 signaling as a key regulator of the transcriptional program in a deacetylase-independent manner during the meiotic-to-postmeiotic transition in spermatogenesis.

Acetyl-L-carnitine (ALC) is an effective substrate for mitochondrial energy metabolism and is known to prevent neurodegeneration and attenuate heavy metal-induced injury. In this study, we investigated the function of ALC in the recovery of mouse spermatogonia cells (GC-1 cells) after heat stress (HS). The cells were randomly divided into three groups: control group, HS group (incubated at 42°C for 90 min), and HS + ALC group (treatment of 150 μM ALC after incubated at 42°C for 90 min). After heat stress, all of the cells were recovered at 37°C for 6 h. In this study, the content of intracellular lactate dehydrogenase (LDH) in the cell supernatant and the malondialdehyde (MDA) levels, catalase (CAT) levels, and total antioxidant capacity (T-AOC) were significantly increased in the HS group compared to the CON group. In addition, the mitochondrial membrane potential (MMP) was markedly decreased, while the apoptosis rate and the expression of apoptosis-related genes (Bcl-2, Bax, and caspase3) were significantly increased in the HS group compared to the CON group. Furthermore, the number of autophagosomes and the expression of autophagy-related genes (Atg5, Beclin1, and LC3II) and protein levels of p62 were increased, but the expression of LAMP1 was decreased in the HS group compared to the CON group. However, treatment with ALC remarkably improved cell survival and decreased cell oxidative stress. It was unexpected that levels of autophagy were markedly increased in the HS + ALC group compared to the HS group. Taken together, our present study evidenced that ALC could alleviate oxidative stress and improve the level of autophagy to accelerate the recovery of GC-1 cells after heat stress.

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