Biomaterial Database

Tsga8 is required for spermatid morphogenesis and male fertility in mice. 2021

Yuki Kobayashi, and Shin-Ichi Tomizawa, and Michio Ono, and Kazushige Kuroha, and Keisuke Minamizawa, and Koji Natsume, and Selma Dizdarević, and Ivana Dočkal, and Hiromitsu Tanaka, and Tatsukata Kawagoe, and Masahide Seki, and Yutaka Suzuki, and Narumi Ogonuki, and Kimiko Inoue, and Shogo Matoba, and Konstantinos Anastassiadis, and Nobuhisa Mizuki, and Atsuo Ogura, and Kazuyuki Ohbo

Department of Histology and Cell Biology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.

During spermatogenesis, intricate gene expression is coordinately regulated by epigenetic modifiers, which are required for differentiation of spermatogonial stem cells (SSCs) contained among undifferentiated spermatogonia. We have previously found that KMT2B conveys H3K4me3 at bivalent and monovalent promoters in undifferentiated spermatogonia. Because these genes are expressed late in spermatogenesis or during embryogenesis, we expect that many of them are potentially programmed by KMT2B for future expression. Here, we show that one of the genes targeted by KMT2B, Tsga8, plays an essential role in spermatid morphogenesis. Loss of Tsga8 in mice leads to male infertility associated with abnormal chromosomal distribution in round spermatids, malformation of elongating spermatid heads and spermiation failure. Tsga8 depletion leads to dysregulation of thousands of genes, including the X-chromosome genes that are reactivated in spermatids, and insufficient nuclear condensation accompanied by reductions of TNP1 and PRM1, key factors for histone-to-protamine transition. Intracytoplasmic sperm injection (ICSI) of spermatids rescued the infertility phenotype, suggesting competency of the spermatid genome for fertilization. Thus, Tsga8 is a KMT2B target that is vitally necessary for spermiogenesis and fertility.

UI	MeSH Term	Description	Entries
D007248	Infertility, Male	The inability of the male to effect FERTILIZATION of an OVUM after a specified period of unprotected intercourse. Male sterility is permanent infertility.	Sterility, Male,Sub-Fertility, Male,Subfertility, Male,Male Infertility,Male Sterility,Male Sub-Fertility,Male Subfertility,Sub Fertility, Male
D008297	Male		Males
D009698	Nucleoproteins	Proteins conjugated with nucleic acids.	Nucleoprotein
D011495	Histone-Lysine N-Methyltransferase	An enzyme that catalyzes the methylation of the epsilon-amino group of lysine residues in proteins to yield epsilon mono-, di-, and trimethyllysine.	Protein Lysine Methyltransferase,Protein Methylase III,Protein Methyltransferase III,Histone-Lysine Methyltransferase,Histone Lysine Methyltransferase,Histone Lysine N Methyltransferase,Methyltransferase, Histone-Lysine,Methyltransferase, Protein Lysine,N-Methyltransferase, Histone-Lysine
D005260	Female		Females
D005298	Fertility	The capacity to conceive or to induce conception. It may refer to either the male or female.	Fecundity,Below Replacement Fertility,Differential Fertility,Fecundability,Fertility Determinants,Fertility Incentives,Fertility Preferences,Fertility, Below Replacement,Marital Fertility,Natural Fertility,Subfecundity,World Fertility Survey,Determinant, Fertility,Determinants, Fertility,Fertility Determinant,Fertility Incentive,Fertility Preference,Fertility Survey, World,Fertility Surveys, World,Fertility, Differential,Fertility, Marital,Fertility, Natural,Preference, Fertility,Preferences, Fertility,Survey, World Fertility,Surveys, World Fertility,World Fertility Surveys
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013087	Spermatids	Male germ cells derived from the haploid secondary SPERMATOCYTES. Without further division, spermatids undergo structural changes and give rise to SPERMATOZOA.	Spermatoblasts,Spermatid,Spermatoblast
D013091	Spermatogenesis	The process of germ cell development in the male from the primordial germ cells, through SPERMATOGONIA; SPERMATOCYTES; SPERMATIDS; to the mature haploid SPERMATOZOA.	Spermatocytogenesis,Spermiogenesis
D013093	Spermatogonia	Euploid male germ cells of an early stage of SPERMATOGENESIS, derived from prespermatogonia. With the onset of puberty, spermatogonia at the basement membrane of the seminiferous tubule proliferate by mitotic then meiotic divisions and give rise to the haploid SPERMATOCYTES.	Spermatophores,Spermatogonias,Spermatophore