AUTHOR=Asmat Mohd Shamoon , Zheng Xiang Yu , Nauman Mohd , Zheng Deyou , Stanley Pamela 

TITLE=Deletion of Mgat2 in spermatogonia blocks spermatogenesis

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 12 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2024.1428715

DOI=10.3389/fcell.2024.1428715

ISSN=2296-634X

ABSTRACT=Identifying factors required for spermatogenesis is important for understanding mechanisms of male fertility. Inactivation of either the Mgat1 or Man2a2 gene leads to a block in spermatogenesis causing infertility in male mice. MGAT1 GlcNAc-transferase initiates complex N-glycan synthesis and MAN2A2 mannosidase generates the substrate for MGAT2 GlcNAc-transferase to form a biantennary complex N-glycan. In this paper we show that conditional deletion of Mgat2 in spermatogonia via Stra8-iCre caused a novel block in spermatogenesis, largely prior to the formation of round spermatids. Mgat2[-/-] germ cells did not bind the lectins Phaseolus vulgaris leukoagglutinin (L-PHA) of Griffonia simplicifolia II (GSA-II)L-PHA or GSA-II, similar to germ cells lacking MGAT1 and complex N-glycans. However, overall spermatogenic defects were distinct in germ cells following deletion ofwith deleted Mgat2 versus Mgat1 in germ cells. In addition, RNA-seq analysis at 15 days after birth revealed a unique transcriptomic landscape in Mgat2[-/-] germ cells with genes required for sperm formation and functions being most down-regulated. Bioinformatic analyses using the Ingenuity Pathway Analysis (IPA) algorithm identified ERK and AKT as central activities. Western blot analyses of 15-day germ cell lysates confirmed that both AKT and ERK1/2 signaling were increased by loss of MGAT2 in germ cells. By contrast, Mgat1[-/-] germ cells were previously shown to have reduced ERK signaling and unchanged AKT activity. Therefore, sincewhile the loss of all complex N-glycans is common to each mutant model, the different spermatogenic defects observed appear to arise from the different immature N-glycans that accumulate in Mgat2[-/-] versus Mgat1[-/-] germ cells are proposed to be the basis of their unique spermatogenic phenotypes..