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Male germ cells are sensitive to heat stress and testes must be maintained outside the body for optimal fertility. However, no germ cell intrinsic mechanism that protects from heat has been reported. Here, we identify the germ cell specific Golgi glycoprotein MGAT4D as a protector of male germ cells from heat stress.  Mgat4d  is highly expressed in spermatocytes and spermatids. Unexpectedly, when the  Mgat4d  gene was inactivated globally or conditionally in spermatogonia, or mis-expressed in spermatogonia, spermatocytes or spermatids, neither spermatogenesis nor fertility were affected. On the other hand, when males were subjected to mild heat stress of the testis (43 °C for 25 min), germ cells with inactivated  Mgat4d  were markedly more sensitive to the effects of heat stress, and transgenic mice expressing  Mgat4d  were partially protected from heat stress. Germ cells lacking  Mgat4d  generally mounted a similar heat shock response to control germ cells, but could not maintain that response. Several pathways activated by heat stress in wild type were induced to a lesser extent in  Mgat4d [−/−] heat-stressed germ cells (NFκB response, TNF and TGFβ signaling,  Hif1α  and  Myc  genes). Thus, the Golgi glycoprotein MGAT4D is a novel, intrinsic protector of male germ cells from heat stress.

The Golgi Glycoprotein MGAT4D is an Intrinsic Protector of Testicular Germ Cells From Mild Heat Stress