Improvement of assisted reproductive techniques by phospholipase A2: the primate assay. – LUTINFER

Currently, assisted reproductive techniques (ART) are widely used in human reproduction and more than 2% of children are born using these techniques in Western countries. In vitro fertilization (IVF) was a major discovery and allowed for infertile parents to obtain children. IVF is based on the mixing of two types of gametes, which are spermatozoa and oocytes. The fusion of both gametes gives rise to embryos, which are then transferred into female tract. The rate of success for embryo outcome is low, around 50%. The rate of babies born after embryos transfer is even lower since only 10% of embryos transferred give rise to a baby. In 1992, a new technique arose, called ICSI (for Intra Cytoplasmic Sperm Injection) and allowed to help efficiently human male with severe sperm defects like asthenozoospermia or oligozoospermia. Although important progresses have been performed, many infertile couples are unable to get children. Moreover, the risk for babies born from ART for having a rare genetic disease is higher, although it remains very low. Several causes have been suggested for such an increase, among which a defective sperm selection due to the ART in comparison to the natural selection which involves several steps like sperm motility, capacitation or acrosome reaction. In this context, the choice of sperm used during ART is a crucial step and the question of sperm features used to select them is important.
We have demonstrated that a peculiar phospholipase, located inside the spermatozoa and released during an exocytotic event occurring at capacitation, is able to discard a subfertile subpopulation of sperm in mice (Escoffier et al, JCI, 2010). The treatment of sperm with such an enzyme allows increasing the fertilization rate and promotes a normal embryo development. A patent, called « Fertilization modulation compounds & process for implementing them » has been registered at an international level, in order to protect this kind of molecules or their metabolites in sperm sorting in ART. The aim of this proposal is to confirm these results in a primate model, in order to bring this discovery to a potential human drug level.
This application focus thus on an optimization of the IVF techniques, based on an original strategy involving a physiological process based on phospholipase A2. The probability of success is rather high because we have a strong experience in phospholipase production and the pharmacological effects of phospholipase of group X in mouse fertilization are robust.
We hope that our work may improve IVF efficiency and thus promote its use. Moreover, this strategy may also help to select sperm in ICSI.
This application is based on the scientific complementary of two research groups, one very skilled in reproduction field and more particularly on sperm physiology (Christophe Arnoult group; partner 1, « Génétique Infertilité et thérapeutique » currently located at Grenoble institute of neuroscience, and the other, leader in the phospholipase A2 domain (Gérard Lambeau ; partner 2 « Physiopathologie Moléculaire des phospholipases A2 et de leurs médiateurs » located at Sophia Antipolis at the “Molecular and cellular pharmacology institute”. These two groups will be supported by Floralis, for the technology transfer, Floralis developing links between the public research carried out at the Joseph Fourier University and the business world.