Seminal Vesicle Secretion 2 Acts as a Protectant of Sperm Sterols and Prevents Ectopic Sperm Capacitation in Mice1

Abstract

Seminal vesicle secretion 2 (SVS2) is a protein secreted by the mouse seminal vesicle. We previously demonstrated that SVS2 regulates fertilization in mice; SVS2 is attached to a ganglioside GM1 on the plasma membrane of the sperm head and inhibits sperm capacitation in in vitro fertilization as a decapacitation factor. Furthermore, male mice lacking SVS2 display prominently reduced fertility in vivo, which indicates that SVS2 protects spermatozoa from some spermicidal attack in the uterus. In this study, we tried to investigate the mechanisms by which SVS2 controls in vivo sperm capacitation. SVS2-deficient males that mated with wild-type partners resulted in decreased cholesterol levels on ejaculated sperm in the uterine cavity. SVS2 prevented cholesterol efflux from the sperm plasma membrane and incorporated liberated cholesterol in the sperm plasma membrane, thereby reversibly preventing the induction of sperm capacitation by bovine serum albumin and methyl-beta-cyclodextrin in vitro. SVS2 enters the uterus and the uterotubal junction, arresting sperm capacitation in this area. Therefore, our results show that SVS2 keeps sterols on the sperm plasma membrane and plays a key role in unlocking sperm capacitation in vivo.

Testicular Dysgenesis Syndrome and Long-Lasting Epigenetic Silencing of Mouse Sperm Genes Involved in the Reproductive System after Prenatal Exposure to DEHP

“…The prostate specific antigen ( Pate 4 or Svs 7) rapidly cleaves both semenogelin-1 and -2 and results in semen liquefaction, the initiation of sperm motility, and the production of a peptide presenting antibacterial activity [48]. Furthermore, Svs 2 (semenogelin-1) attached to ganglioside GM1 on the plasma membrane of the sperm head maintain sterols in place and prevent sperm capacitation in a wrong location or at a wrong time [49]. Interestingly, Svs 2 knockout male mice were sub-fertile; their sperm did not form plugs and did not survive to artificial insemination [50].…”

Flagellar hyperactivation of bull and boar spermatozoa

“…One of the changes which are observed during early stage of capacitation is release of decapacitation factors from sperm surface. So far, surface coating proteins (eg acrosomal stabilizing factor and seminal vesicle secretions) and lipids (eg cholesterol), which stabilize sperm membranes, have been identified as decapacitation factors. As explained previously, seminal vesicle secretion 2 (SVS2) is one of major proteins secreted from mouse seminal vesicle and exposed to spermatozoa at ejaculation.…”

“…So far, surface coating proteins (eg acrosomal stabilizing factor and seminal vesicle secretions) and lipids (eg cholesterol), which stabilize sperm membranes, have been identified as decapacitation factors. As explained previously, seminal vesicle secretion 2 (SVS2) is one of major proteins secreted from mouse seminal vesicle and exposed to spermatozoa at ejaculation. In the uterus, SVS2 attaches to spermatozoa via the plasma membrane ganglioside GM1 probably in order to protect sterols (including cholesterol) in the sperm plasma membrane.…”

Relationship between Semenogelins bound to human sperm and other semen parameters and pregnancy outcomes

“…No parameters, including the proportion of SEMG+/− and total SEMG+/− count, demonstrated significant differences between the two groups (Table 3 ). Then, we examined whether there were differences in SEMG+/− and/or other parameters between the two groups (pregnancy established with sperm passing through the uterus and oviduct (spontaneous and IUI, in vivo fertilization) versus pregnancy established without sperm passage into the uterus (IVF or ICSI, in vitro fertilization)), since SEMGs are considered to suppress the process of ectopic capacitation in uterus and to be removed from the surface of sperm in oviduct during in vivo fertilization [ 13 – 15 ]. We compared the summed data of spontaneous pregnancy and IUI to that of IVF and ICSI (Table 4 ).…”

“…SVS2 is thought to be a protector against spermicidal agents in the uterus, and to be removed from the sperm’s surface after passing through the isthmus [ 14 ]. Coincidently, the removal of SVS2 induces the decrease of cholesterol from the sperm membrane, thereby resulting in the ability of sperm to fertilize the egg [ 15 ]. The data in this study indicate that a patient with a larger number of spermatozoa with removed SEMGs can be involved in a successful pregnancy via in vivo fertilization.…”