Abstract
Testis-specific PRSS55 is a highly conserved chymotrypsin-like serine protease among mammalian species. So far, the physiological function of PRSS55 remains unknown. Here, we show that PRSS55 is a GPI-anchored membrane protein, specifically expressed in adult mouse testis and mainly observed in the luminal side of seminiferous tubules and sperm acrosome. Mice deficient for Prss55 develop male infertile with normal reproduction-related parameters observed. Interestingly, in vivo fertilization rate of Prss55−/− males is dramatically decreased, possibly due to incapable migration of Prss55−/− sperm from uterus into oviduct. However, in vitro fertilization rate has no difference between two genotypes although Prss55−/− sperm presents defective recognition/binding to zona-intact or zona-free oocytes. Further study reveals that mature ADAM3 is almost undetectable in Prss55−/− sperm, while precursor ADAM3 remains unchanged in the testis. However, it is shown that ADAM3 has no interaction with PRSS55 by immunoprecipitation with anti-PRSS55 antibody. The expression levels of several proteins known to be related to the observed phenotypes remain comparable between wt and Prss55−/− mice. Moreover, we found that Prss55 deficiency has no effect on PRSS37 or vice versa albeit two mutant males share almost the same phenotypes. Microarray analysis reveals a total of 72 differentially expressed genes in Prss55−/− testis, most of which are associated with cellular membrane and organelle organization, protein transport and complex assembly, and response to stimulus and signaling. In conclusion, we have demonstrated that PRSS55 plays vital roles in regulating male fertility of mice, including in vivo sperm migration and in vitro sperm–egg interaction, possibly by affecting the maturation of ADAM3 in sperm and the expression of multiple genes in testis.
Highlights
The in vivo fertilization of mammalians is a complex process containing several coordinated events
Clgn and Calr3 encode testis-specific endoplasmic reticulum (ER) chaperones; ADAM1A, ADAM2 and ADAM3 are three members of the ADAM family that is composed of structurally related cell surface proteins proposed to have cell adhesion activity; TPST2 catalyzes post-translational protein tyrosine O-sulfation; PDILT cooperates with CALR3 in the ER and functions in the disulfide-bond formation; Rnase10, a pancreatic Rnase A homolog, encodes a secreted proximal epididymal protein in the mouse; PRSS37 is a putative trypsin-like serine protease exclusively expressed during a short time range of late spermiogenesis and does not exist in mature mouse sperm; TEX101/LY6K, a glycosylphosphatidylinositol (GPI)-anchored protein complex expressed in testicular germ cells, interacts with precursor ADAM3 in the testis and is a tACE-specific substrate
The tissue expression profile of Prss55 in the mouse was examined by both semi-quantitative and real-time RT-PCR. cDNAs were prepared from 16 mouse tissues including cerebrum, cerebellum, lung, thymus, heart, spleen, liver, pancreas, small intestine, kidney, skeletal muscle, gall bladder, ovary, uterus, epididymis, and testis
Summary
The in vivo fertilization of mammalians is a complex process containing several coordinated events. Over the past two decades, a number of genes have been verified to play essential roles in regulating this process using genetically manipulated mouse models, including Clgn [3, 4], Calr3 [5], Adam1a [6], Adam2 [7], Adam3 [8, 9], t-Ace [10], Tpst2 [11, 12], Pdilt [13], Rnase10 [14], Pmis2 [15], Prss37 [16], Tex101 [17, 18] and Ly6k [18] These gene-encoded proteins are varied in cellular component and molecular function. The ongoing efforts to identify such genes are of great significance since they may be potential causes of unexplained male infertility (UMI) in men and be potential targets for the development of new drugs for both the treatment of UMI and male contraception
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
