TY - JOUR
T1 - The Golgi Glycoprotein MGAT4D is an Intrinsic Protector of Testicular Germ Cells From Mild Heat Stress
AU - Akintayo, Ayodele
AU - Liang, Meng
AU - Bartholdy, Boris
AU - Batista, Frank
AU - Aguilan, Jennifer
AU - Prendergast, Jillian
AU - Sabrin, Afsana
AU - Sundaram, Subha
AU - Stanley, Pamela
N1 - Funding Information:
We thank Frederic Bard for helpful comments on the manuscript, and the Histopathology Core, the Flow Cytometry core, the Transgenic Mouse and Gene Targeting Facilities and the Analytical Imaging Core of the Albert Einstein College of Medicine, who performed core services supported by Albert Einstein Cancer Center grant P01 13330. Funder, Grant reference number, Author: National Institute of General Medical Sciences, RO1 GM105399, Pamela Stanley. Mizutani Foundation, Not applicable, Pamela Stanley. National Cancer Institute, PO1 13330, David Goldman. The funders had no role in study design, data collection or interpretation, or the decision to submit the work for publication.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-020-58923-6
DO - 10.1038/s41598-020-58923-6
M3 - Article
C2 - 32034218
AN - SCOPUS:85079081952
SN - 2045-2322
VL - 10
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 2135
ER -