Improved outcome of artificial insemination and in vitro fertilization by increasing male fertility

Introduction

About 15% of couples have infertility problems, half of which is due to deficiencies of man. Despite undeniable progress, many infertile couples fail to conceive. Moreover, the risk of giving birth to a child with a rare genetic disease, although very low, is significantly higher in children born using ART. Several reasons were cited including a higher risk of defective sperm selection in ART compared to processes of natural selection. In this context, the quality of gametes is of particular importance. The discovery described below, if transposed to humans, would enable to select the best sperm quality for ART. If transposed to other animals, this technology would improve the yield of artificial insemination techniques.

Service Offerings

The existence of a physiological mechanism that can target and eliminate a subpopulation of subfertile sperm with abnormal lipid component on their plasma membrane was recently demonstrated in the mouse species (Escoffier et al., JCI, 2010).

Pictures of embryo development 24 h after fertilization: (+/+), WT sperm crossed with WT oocytes; (-/-), mGX-/- sperm crossed with WT oocytes; arrows show unfertilized oocytes and asterix shows aborted embryo (from Escoffier et al., JCI, 2010).

After entering the female reproductive tract, subfertile sperm cells release during their maturation an enzyme called group X secreted phospholipase A2. This latter further eliminates subfertile sperm by destroying their sperm acrosome, making them unable to fuse with the ovocyte. These subfertile sperm cells are thus rendered fully infertile and excluded from the «race to fertilization”.

This mechanism is supported by in vitro and in vivo experiments in the mouse species showing that the absence of group X secreted phospholipase A2 (mGX) in genetically modified animals or its inhibition by specific antagonists (data not shown) decrease the fertilization rate and alters embryonic development.

Conversely, when the sperm cell population is treated with recombinant mGX sPLA2, there is a significant increase of the fertilization rate, as high as 30% in a very fertile mouse model (OF1 outbred mice, figure 2) and 100% in a model of subfertile mouse (inbred C57Bl6/J mouse in which the reproductive rate is low).

Exogenous mGX improves fertility outcome. During in vitro fertilization, treatment of sperm with recombinant mGX leads to a significant increase of the fertilization rate and improves embryo development in mice.

Key Benefits

The present technology aims to provide a treatment for sterility or a treatment for promoting and improving fertilization by:

• Improving sperm maturation,
• Increasing the rate of fertilization,
• Reducing the risk of fertilization with a defective sperm,
• Allowing for selection of fertile spermatozoa,
• Promoting the embryogenesis, in particular viable embryogenesis, and without presenting genetic abnormality.

Applications

• Assisted Reproductive Technology (human medicine),
• Artificial Insemination (veterinary medicine),
• Contraception.

IP Status

A patent application has been filed on March 24, 2009. Publication number: WO2010108942

Commercial Opportunities