Members of the murine Pate family are predominantly expressed in the epididymis in a segment-specific fashion and regulated by androgens and other testicular factors

Abstract

BackgroundSpermatozoa leaving the testis are not able to fertilize the egg in vivo. They must undergo further maturation in the epididymis. Proteins secreted to the epididymal lumen by the epithelial cells interact with the spermatozoa and enable these maturational changes, and are responsible for proper storage conditions before ejaculation. The present study was carried out in order to characterize the expression of a novel Pate (prostate and testis expression) gene family, coding for secreted cysteine-rich proteins, in the epididymis.MethodsMurine genome databases were searched and sequence comparisons were performed to identify members of the Pate gene family, and their expression profiles in several mouse tissues were characterized by RT-PCR. Alternate transcripts were identified by RT-PCR, sequencing and Northern hybridization. Also, to study the regulation of expression of Pate family genes by the testis, quantitative (q) RT-PCR analyses were performed to compare gene expression levels in the epididymides of intact mice, gonadectomized mice, and gonadectomized mice under testosterone replacement treatment.ResultsA revised family tree of Pate genes is presented, including a previously uncharacterized Pate gene named Pate-X, and the data revealed that Acrv1 and Sslp1 should also be considered as members of the Pate family. Alternate splicing was observed for Pate-X, Pate-C and Pate-M. All the Pate genes studied are predominantly expressed in the epididymis, whereas expression in the testis and prostate is notably lower. Loss of androgens and/or testicular luminal factors was observed to affect the epididymal expression of several Pate genes.ConclusionsWe have characterized a gene cluster consisting of at least 14 expressed Pate gene members, including Acrv1, Sslp1 and a previously uncharacterized gene which we named Pate-X. The genes code for putatively secreted, cysteine-rich proteins with a TFP/Ly-6/uPAR domain. Members of the Pate gene cluster characterized are predominantly expressed in the murine epididymis, not in the testis or prostate, and are regulated by testicular factors. Similar proteins are present in venoms of several reptiles, and they are thought to mediate their effects by regulating certain ion channels, and are thus expected to have a clinical relevance in sperm maturation and epididymal infections.

Segment-specific regulation of epididymal gene expression

“…Many genes exhibit cell type and segment-specific expression patterns, where expression can be restricted to one particular subsegment. Additionally, several gene families, for example, prostate and testis expression (Pate, Turunen et al 2011) and wingless-type MMTV integration site family (Wnt, Koch et al 2015), display distinct expression patterns along the tissue; certain family members are restricted to specific epididymal regions, whereas other members are present in the whole tissue (Fig. 2).…”

Effect of immunization against prostate- and testis-expressed (PATE) proteins on sperm function and fecundity in the rat

“…Sperm maturation is facilitated by a number of proteins secreted by the epididymal epithelial cells into the luminal fluid, which then bind on to the sperm surface (Ducheux et al, 2003). Defensins (Yenugu et al, 2004(Yenugu et al, , 2006Travis et al, 2000), members of the sperm-associated antigen 11 family (Hamil et al, 2000), lysozymes Mandal et al, 2003), lipocalins (Hamil et al, 2003), cathelicidins, protease inhibitors Blankenvoorde et al, 1998;Hiemstra et al, 1996), inhibitors of complement lysis (Collard and Griswold, 1987;Griswold et al, 1986), the cysteine-rich proteins such as CRISPs (Jalkanen et al, 2005;Luo et al, 2012), and members of the prostate-and testis-expressed (PATE) family (Bera et al, 2002;Soler-Garcia et al, 2005;Levitin et al, 2008;Turunen et al, 2011) are some examples of a wide range of proteins that bind to the sperm surface . Further, a variety of factors secreted by the seminal vesicles and prostate also aid in the formation of functional http://dx.doi.org/10.1016/j.jri.2015.02.009 0165-0378/© 2015 Elsevier Ireland Ltd. All rights reserved.…”

“…In the human and mouse, the Pate gene cluster is present on chromosomes 11 and 9 respectively (Levitin et al, 2008;Bera et al, 2002;SolerGarcia et al, 2005;Turunen et al, 2011). Although the Pate genes were initially thought to be prostate-and testisspecific, a recent study indicated their expression in the epididymis and not in the testis and prostate (Turunen et al, 2011).…”

“…In the human and mouse, the Pate gene cluster is present on chromosomes 11 and 9 respectively (Levitin et al, 2008;Bera et al, 2002;SolerGarcia et al, 2005;Turunen et al, 2011). Although the Pate genes were initially thought to be prostate-and testisspecific, a recent study indicated their expression in the epididymis and not in the testis and prostate (Turunen et al, 2011). We reported that the rat Pate genes were found to be expressed in the seminal vesicle and epididymis and in tissues beyond the male reproductive tract; and their expression seems to be androgen-dependent (Rajesh and Yenugu, 2012).…”

“…Although few studies have reported that the PATE proteins are localized in the male reproductive tissues and spermatozoa (Soler-Garcia et al, 2005;Turunen et al, 2011;Margalit et al, 2012;Levitin et al, 2008), their precise function is not yet known. Among the ten rat Pate genes identified, we focused on the characterization of two of them; namely, Pate and Pate-F, since the mRNA expression of Pate is restricted to corpus and cauda and that of Pate-F was specific to the caput (Rajesh and Yenugu, 2012).…”