A. Saewu

D. Burger

F. Compostella

H. Xu

K. Faull

K. Kongmanas

L. Panza

N. Tanphaichitr

W. Kiattiburut

English

AIR Universita degli studi di Milano

ID: 21368
PROPERTY, METABOLISM AND ROLES OF SULFOGALACTOSYLGLYCEROLIPID IN
REPRODUCTION
N. Tanphaichitr 1, K. Kongmanas 1, A. Saewu 1, H. Xu 1, W. Kiattiburut 1, D. Burger 1, K. Faull 4, F. Compostella
2, L. Panza 3
1Ottawa Hospital Research Institute, University of Ottawa
2Università degli Studi di Milano
3Università del Piemonte Orientale
4University of California, Los Angeles
Sulfogalactosylglycerolipid (SGG, aka seminolipid) is expressed selectively in mammalian male germ
cells. SGG biosynthesis occurs in testicular germ cells (TGCs) in both pachytene spermatocytes and
round spermatids. Alkylacylglycerol (mainly palmitylpalmitoylglycerol-PPG), SGG’s lipid backbone,
is first galactosylated by ceramide galactosyltransferase to form galactosylglycerol (GG), which is then
sulfated by cerebroside sulfotransferase to become SGG. Our biophysical studies indicate that SGG is an
ordered lipid, having propensity to interact with cholesterol. Together with cholesterol, most of SGG on
sperm exists in sperm lipid rafts, which have direct affinity for the egg zona pellucida (ZP). On the sperm
surface, SGG co-exists with arylsulfatase A (ARSA), which also has direct ZP binding ability. Therefore
SGG and ARSA likely act synergistically in sperm-egg interaction. Their co-existence on the sperm
surface is due to the binding of SGG to the surface cleft of ARSA. SGG also interacts with high affinity
to the active site pocket of lysosomal ARSA, resulting in SGG desulfation. In testicular seminiferous
tubules (SFTs), ARSA exists in lysosomes of Sertoli cells, which are somatic cells that are important
for development of TGCs into sperm. Sertoli cells are also engaged in phagocytosing residual bodies
(excess cytoplasmic components of elongating spermatids) for mature sperm formation. As well, Sertoli
cells phagocytose apoptotic germ cells, which amount to 50% of total TGCs. Both residual bodies and
apoptotic germ cells contain SGG. Our studies using Arsa knockout mice indicate that phagocytosed
SGG is targeted to Sertoli cell lysosomes for desulfation by ARSA. Presumably, galactosylceramidase
would then degalactosylate GG to the backbone lipid, PPG, which can be shuttled to adjacent TGCs for
a new round of SGG biosynthesis. In Arsa null mice, SGG desulfation does not occur resulting in its
intracellular accumulation, a condition that is toxic to Sertoli cells. Arsa-/- Sertoli cells produce higher
levels of H2O2 than age-matched wild type mice. H2O2 would harm developing TGCs and Sertoli cells
themselves. These accruing effects lead to decreased numbers of viable TGCs, increased numbers of
abnormal sperm, decreased numbers of Sertoli cells and subsequently subfertility of aging Arsa-/- male
mice. Our results indicate the importance of sperm SGG in fertilization as well as SGG degradation in
Sertoli cells in maintaining male fertility.


Property, metabolism and roles of sulfogalactosylglycerolipid in reproduction

https://air.unimi.it/retrieve/handle/2434/690663/1349647/Glyco25abstract_Nuch.pdf

Property, metabolism and roles of sulfogalactosylglycerolipid in reproduction

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