New Wenshen Shengjing Decoction Improves Early Embryonic Development by Maintaining Low Levels of H3K4me3 in Sperm

Abstract

Background. New Wenshen Shengjing Decoction (NWSSJD), a traditional Chinese compound medicine, has significant effect on spermatogenesis disorder and can significantly improve sperm quality. Many components in NWSSJD can induce epigenetic modifications of different types of cells. It is not yet known whether they can cause epigenetic modifications in sperm or early embryos. Objective. This study investigated the effect of NWSSJD on mouse early embryonic development and its regulation of H3K4me3 in mouse sperm and early embryos. Methods. Spermatogenesis disorder was induced in male mice with CPA (cyclophosphamide). NWSSJD was administrated for 30 days. Then, the male mice were mated with the female mice with superovulation, and the embryo degeneration rate of each stage was calculated. Immunofluorescence staining was used to detect the expression of H3K4me3 in sperm and embryos at various stages. Western blotting was performed to detect methyltransferase SETD1B expression. The expressions of development-related genes (OCT-4, NANOG, and CDX2) and apoptosis-related genes (BCL-2 and p53) were measured with qRT-PCR. Results. Compared with the CPA group, NWSSJD significantly reduced the H3K4me3 level in sperms, significantly increased the number of normal early embryos (2-cell embryos, 3-4-cell embryos, 8-16-cell embryos, and blastocysts) per mouse, and reduced the degeneration rate of the embryos. The expression levels of H3K4me3 and methyltransferase SETD1B in early embryos were significantly elevated by NWSSJD. Additionally, NWSSJD significantly promoted BCL-2 expression, while reducing p53 expression, thus inhibiting embryonic cell apoptosis. Moreover, the expressions of development-related genes OCT-4 and CDX2 were significantly increased by NWSSJD, but NANOG expression had no significant difference. Conclusion. NWSSJD may promote early embryonic development possibly by maintaining low H3K4me3 levels in sperms and normal H3K4me3 modification in early embryos and by inhibiting embryonic cell apoptosis.

Role and Mechanism of Epigenetic Regulation in the Aging of Germ Cells: Prospects for Targeted Interventions

“…Additionally, it could maintain SSCs, significantly reduced the mean percentage of ubiquitination and DNA breaks in sperm, as well as improved chromatin integrity, testicular organization, and spermatogenesis [100]. A traditional Chinese compound medicine called New Wenshen Shengjing Decoction was found to significantly reduce the level of H3K4me3 in mouse spermatozoa, thereby enhancing fertility [101]. Interestingly, the bacterium Lactobacillus rhamnosus reversed the increased miRNA (miR-155-5p, miR-26a-5p, miR-21-5p, miR-200c-3p, and miR-let7a-5p) and DNMT1 expression in spermatozoa induced by a high-fat diet [102].…”

“…Reducing H3K4me3 levels in sperm Inhibiting embryonic cell apoptosis to promote early embryonic development [101]…”