Abstract
Sphingomylin participates in sperm function in animals, and also regulates the Akt and ERK signaling pathways, both of which are associated with the asthenospermia. Sphingomyelin synthase 2 (SMS2) is involved in the biosynthesis of sphingomylin. To determine the relationship between SMS2 and human sperm function, we analyzed the distribution of SMS2 in human sperm and testes, and SMS2 expression in patients with asthenospermia and normozoospermia; human sperm were treated with anti-SMS2, and the sperm motility, penetration ability into methylcellulose, capacitation and acrosome reaction, and sperm [Ca2+]i imaging were evaluated, while the Akt and ERK pathway and cleaved caspase 3 were also analyzed. Results showed that SMS2 was localized in the testis and human sperm, and the protein levels of normozoospermia were higher than asthenospermia. Inhibition of SMS2 activity significantly decreased sperm motility and penetration ability into methylcellulose, but had no influence on capacitation and acrosome reaction, or on intracellular [Ca2+]i compared to IgG-treated control groups. Moreover, the phosphorylation level of Akt was decreased, whereas the phosphorylation of ERK and cleaved-caspase 3 levels were significantly increased. Taken together, SMS2 can affect sperm motility and penetration ability into methylcellulose, and participate in apoptosis associated with the Akt and ERK signaling pathways.
Highlights
Infertility is a common reproductive disease, and male infertility accounts for half of the cases [1].A significant proportion of male infertility cases is accompanied by abnormal semen quality including asthenospermia, teratospermia, oligozoospermia, and azoospermia [1]
Since SM is the main component of cellular membranes and Sphingomyelin synthase 2 (SMS2) is the major enzyme catalyzing SM biosynthesis, we measured the expression of SMS2 in testis and sperm cells by immunohistochemistry and immunofluorescence, respectively
Thereafter, we investigated the expression of SMS2 in the human sperm cells by immunofluorescence
Summary
A significant proportion of male infertility cases is accompanied by abnormal semen quality including asthenospermia, teratospermia, oligozoospermia, and azoospermia [1]. Asthenospermia, which is associated with poor sperm viability and motility, is the leading factor in male infertility [1,2]. Many causes of asthenospermia have been reported so far [3,4,5], which include dysplasia of fibrous sheath, defects in the action of cilium, disfunction of energy metabolism, dysplasia of calcium channel [3,4]. Some reports indicated that the viability and motility of sperm cells are tightly related with the activation of the Akt signaling pathway, whereas oxidative stress, drugs, and ischemic injury are the factors that can inhibit the Akt signal pathway by blocking its phosphorylation, leading to reduced viability and motility of the Molecules 2020, 25, 4231; doi:10.3390/molecules25184231 www.mdpi.com/journal/molecules
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