CANCELLED [SCAN] Positive effects of starvation on sperm fertility potential

Title: Positive effects of starvation on sperm fertility potential

Speaker: Alberto Darszon, Instituto de Biotecnología, Genética del Desarrollo y Fisiología Molecular Universidad Nacional Autónoma de México

Abstract: Fertilization is a matter of life and death and an attractive and fundamental process for studying cellular interactions. Although the factors mediating the sperm-egg dialogue have been studied for a century, the detailed molecular mechanisms involved in these events remain incomplete. Ion channels and transporters are deeply involved in gamete signaling and participate in fundamental sperm functions such as regulated motility, maturation, and the acrosome reaction (AR). Knock-out mice models lacking certain ion channels and transporters (e.g. the sperm-specific Ca2+ channel complex CatSper) are sterile. Similarly, many ion channel and transporter inhibitors cause infertility.

We have recently reported two different methodologies that improve sperm functionality: 1) transiently exposing sperm to the Ca2+ ionophore A23187, and 2) sperm incubation in the absence of energy nutrients (starvation, STRV). Both methods initially stop motility, which can be recovered either removing the ionophore or adding substrates to the starving sperm. The two procedures elevate intracellular Ca2+ ([Ca2+]i) and pH (pHi) and hyperpolarize the cells (their interior becomes electrically more negative). Interestingly, both protocols when reversed yield a significantly higher percentage of sperm with hyperactivated motility that display an increased ability to fertilize eggs in vitro. Remarkably, the effects of this treatment continue beyond fertilization as starved and rescued sperm promote higher rates of embryo development, and once transferred to pseudo-pregnant females, blastocysts derived from treated sperm produce significantly more pups. The starvation and rescue protocol increase fertilization and embryo development even in sperm from severely sub fertile mouse models, and when combined with temporal increase in [Ca2+]i, this methodology significantly improved fertilization and embryo development rates in sperm of sterile CatSper1 KO mice model.

The starved sperm display a potentiated ability to undergo a progesterone-induced acrosome reaction (AR) and increased total ion cell currents.  We have discovered that Cl- channels of the TMEM16 family activate as [Ca2+]i increases during sperm starving and that these channels participate in the AR.