The Golgi Glycoprotein MGAT4D Protects Testicular Germ Cells From Mild Heat Stress

MGAT4D was identified as an inhibitor of MGAT1 in the Golgi of transfected cells. MGAT1 is the GlcNAc-transferase that initiates complex and hybrid N-glycan synthesis in mammals. Conditional deletion of in spermatogonia leads to a block in spermatogenesis and infertility in mice. is highly expressed in spermatocytes and spermatids. Here we show that, unexpectedly, when the gene was inactivated globally or conditionally in spermatogonia, or mis-expressed in spermatogonia, spermatocytes or spermatids, neither spermatogenesis nor fertility were affected. MGAT1 activity was also not inhibited in germ cells. On the other hand, when males were subjected to mild heat stress of the testis (43°C for 25 min), a novel function for MGAT4D was revealed. Germ cells with inactivated were markedly more sensitive to the effects of mild heat stress, and transgenic mice expressing in spermatogonia, spermatocytes or spermatids were partially protected from heat stress. Microarray data from germ cells of heat-stressed mutant versus control males showed that germ cells lacking generally mounted a similar heat shock response to control germ cells, but could not maintain that response. Several pathways and genes activated by heat stress in wild type were induced to a lesser extent in [-/-] heat-stressed germ cells, including the NFκB response, pro-inflammatory pathways such as TNF and TGFβ signaling, and genes that promote proliferation such as and Thus, MGAT4D protects male germ cells from the deleterious consequences of heat stress.