Seminal vesicle protein SVS2 is required for sperm survival in the uterus

Abstract

In mammals, sperm migrate through the female reproductive tract to reach the egg; however, our understanding of this journey is highly limited. To shed light on this process, we focused on defining the functions of seminal vesicle secretion 2 (SVS2). SVS2 −/− male mice produced sperm but were severely subfertile, and formation of a copulatory plug to cover the female genital opening did not occur. Surprisingly, even when artificial insemination was performed with silicon as a substitute for the plug, sperm fertility in the absence of SVS2 remained severely reduced because the sperm were already dead in the uterus. Thus, our results provide evidence that the uterus induces sperm cell death and that SVS2 protects sperm from uterine attack.in vivo fertilization | uterine sperm selection | decapacitation | acrosomal reaction | uterine spermicide

Genetic and phenotypic influences on copulatory plug survival in mice

“…Plug survival was not correlated with either PC1 or PC2 (F 1, 6 = 4.25, 1.55; P = 0.09, 0.26, respectively). Variation in Svs2 did not seem to explain variation in plug mass, and this is surprising given its importance in plug formation (Kawano et al, 2014).…”

“…The full exomes will be published as part of a larger study elsewhere, but we focus here on these five genes as they are either necessary for copulatory plug formation or present in seminal vesicles and plugs at high abundance (Lundwall et al, 1997;Dean et al, , 2011Dean, 2013;Kawano et al, 2014). DNA was sheared using a Bioruptor UCD-200 (Diagenode, Denville, NJ, USA) with 7 rounds of sonication (7 min per round on high, 30 s on and 30 s off) and genomic DNA libraries were constructed using a previously described protocol designed to facilitate multiplexed exome capture (Rohland and Reich, 2012).…”

Seminal vesicle proteins SVS3 and SVS4 facilitate SVS2 effect on sperm capacitation

“…After copulation, SVS2 enters the uterus and attaches to the sperm head in order to protect sperm (Kawano & Yoshida 2007, Kawano et al 2014, Araki et al 2015. To examine whether this is also true for SVS3 and SVS4, we measured SVS3 and SVS4 quantities in each part of the female reproductive tract we collected, 1.5 h after copulation: the copulatory plug, the vagina, the uterine region near the vagina, the uterine region near the oviduct and the oviduct.…”

“…Although decapacitation by various factors has been reported (Dukelow et al 1966, Davis 1974, Reyes et al 1975, Huang et al 1999, Lu et al 2011, Tseng et al 2013, their in vivo functions remain unclear. On the other hand, the seminal vesicle plays an important role in sperm fertility, and the removal of seminal vesicles from mice results in the decline of fertility (Pang et al 1979, Bromfield et al 2014, Kawano et al 2014. Previously, we reported that seminal vesicle secretory protein 2 (SVS2), which is one of the secreted proteins from the seminal vesicle (SVSs), has two effects on sperm capacitation: an inhibitory effect on initiation of capacitation (capacitation inhibitor role) and cancellation of fertility of the capacitated spermatozoa (decapacitation factor role) (Kawano & Yoshida 2007.…”

“…Previously, we reported that seminal vesicle secretory protein 2 (SVS2), which is one of the secreted proteins from the seminal vesicle (SVSs), has two effects on sperm capacitation: an inhibitory effect on initiation of capacitation (capacitation inhibitor role) and cancellation of fertility of the capacitated spermatozoa (decapacitation factor role) (Kawano & Yoshida 2007. Furthermore, Svs2 -/-males showed lower fertility rates due to spermicidal attack in the uterus (Kawano et al 2014). SVS2 binds to the sperm plasma membrane in order to inhibit sterol efflux that accompanies capacitation, resulting in the suppression of ectopic capacitation (Kawano & Yoshida 2007, Araki et al 2015.…”