Sperm nucleus decondensation, hyaluronic acid (HA) binding and oocyte activation capacity: different markers of sperm immaturity? Case reports

Abstract

During the early time of IVF, sperm competence was defined as the ability to fertilize an oocyte. However, with the advent of ICSI, despite the capacity to reach 2–4cell stage, it is impossible for numerous patients, to establish a pregnancy. Instead the consensus now is that male fertility has to be defined as the capacity to produce sperm cells able to establish a full term pregnancy [1–3] Basic parameters such as concentration, motility and morphology are of limited value in determining sperm capacity to allow full embryonic development to term. Determination of DNA changes like fragmentation and condensation are independent parameters [2] and obviously of major importance. DNA fragmentation, related or not to reactive oxygen species (ROS) insult is only one piece of the problem. Indeed, sperm chromatin tertiary structure seems to be critical for correct epigenetic regulation and maintenance, and further on for male fertility [4, 5]. During very early embryogenesis, an adequate chromatin structure is also necessary for the very first cleavages [6–9]. Methylation is one of the most important regulators of the tertiary structure and imprinting; it affects sperm DNA and histones packaging it; in this way a correct recycling of homocysteine is mandatory during spermatogenesis and embryogenesis. The sperm is not just a carrier of paternal genome: it has a relevant epigenetic contribution. A defective wrapping of DNA is often linked to immaturity. Hyaluronic acid (HA) binding ability has been proposed as a tool to select the more mature spermatozoa having reached their final nuclear and cytoplasmic maturation [10, 11], even if controversies exist [12], and it is used as well in veterinary medicine [13]. In this case report we have tested the relation between HA binding and methylation effector supplementation, by comparison to what we have observed with such a supplementation for patients with poor sperm condensation.