SOHLH2 is essential for synaptonemal complex formation during spermatogenesis in early postnatal mouse testes

Abstract

Spermatogenesis- and oogenesis-specific helix-loop-helix transcription factor 2 (SOHLH2) is exclusively expressed in germ cells of the gonads. Previous studies show that SOHLH2 is critical for spermatogenesis in mouse. However, the regulatory mechanism of SOHLH2 during early spermatogenesis is poorly understood. In the present study, we analyzed the gene expression profile of the Sohlh2-deficient testis and examined the role of SOHLH2 during spermatogenesis. We found 513 genes increased in abundance, while 492 genes decreased in abundance in 14-day-old Sohlh2-deficient mouse testes compared to wildtype mice. Gene ontology analysis revealed that Sohlh2 disruption effects the relative abundance of various meiotic genes during early spermatogenesis, including Spo11, Dmc1, Msh4, Prdm9, Sycp1, Sycp2, Sycp3, Hormad1, and Hormad2. Western blot analysis and immunostaining showed that SYCP3, a component of synaptonemal complex, was significantly less abundant in Sohlh2-deficient spermatocytes. We observed a lack of synaptonemal complex formation during meiosis in Sohlh2-deficient spermatocytes. Furthermore, we found that SOHLH2 interacted with two E-boxes on the mouse Sycp1 promoter and Sycp1 promoter activity increased with ectopically expressed SOHLH2. Taken together, our data suggest that SOHLH2 is critical for the formation of synaptonemal complexes via its regulation of Sycp1 expression during mouse spermatogonial differentiation.

Optimal-Transport Analysis of Single-Cell Gene Expression Identifies Developmental Trajectories in Reprogramming

“…A second wave is activated on days 12-14, including Obox6, Sohlh2, Ddit3, and Bhlhe40. Notably, Obox6 and Sohlh2 are not expressed in the trajectories to any other cell fate and have roles in maintenance and survival of germ cells (Park et al, 2016;Rajkovic et al, 2002) but have not been previously implicated in pluripotency.…”

Loss of Cx43 in Murine Sertoli Cells Leads to Altered Prepubertal Sertoli Cell Maturation and Impairment of the Mitosis-Meiosis Switch

“…In a recent study, however, fewer numbers of spermatocytes were also detected in the seminiferous tubules of Sohlh2 KO mice, and SOHLH2 was found to be crucial for synaptonemal complex formation by regulating Sycp1 expression during spermatogonial differentiation and therefore important for progression of meiosis [76].…”

Loss of TDP-43 in male germ cells causes meiotic failure and impairs fertility in mice

“…7 B ). KO of all the aforementioned genes disrupted the formation of SC leading to failure of meiosis ( 35 , 36 , 37 , 38 , 39 , 40 , 41 ). Decreased expression of meiotic genes in cKO testis raises another possibility that TDP-43 deletion may have affected the expression of a master controller of meiosis such as A-myb ( 42 ).…”

“…Loss of TDP-43 also led to reduced expression of a number of other genes important for the progression of meiosis including Sohlh1, Sohlh2, Hormad1, Hormad2, Sycp1, Sycp2, and Sycp3 (Fig 7B). Knockout of all of the above genes disrupted the formation of synaptonemal complex leading to failure of meiosis (36)(37)(38)(39)(40)(41)(42). Decreased expression of meiotic genes in cKO testis raises another possibility that TDP-43 deletion may have affected the expression of a master controller of meiosis such as A-myb (43).…”