Gianpiero D. Palermo
Advancement in the understanding of spermatozoal dysfunction as a contributing factor for fertilization failure
Since the inception of in vitro fertilization, it became clear that proper fertilization of an oocyte requires the presence of a functional spermatozoon. Several factors can indeed interfere with male gamete function. This ranges from immunological factors such as the presence of anti-sperm antibodies to a dysfunction or complete absence of the acrosome. My team has performed several groundbreaking investigations to actually understand the function and at the same time to test methods to enhance acrosomal activity. This work lead to the understanding, together with outstanding researchers in the field, of the area within the sperm nucleus where the soluble cytosolic factor responsible for oocyte activation is located.
Development of the ultimate treatment of human male infertility
Male-factor infertility represents half of the causes for the inability of couples to reproduce. Since 1980, several micro manipulation techniques were attempted to achieve fertilization with gametes from men with severe male-factor infertility. In 1992, I succeeded to report the first four human pregnancies with intracytoplasmic sperm injection (ICSI). With this procedure, couples with almost all aspects of male infertility, from the presence of anti-sperm antibodies to complete absence of the acrosome, can be successfully treated. Indeed, only one spermatozoon is required, as long as it is viable, to be able to achieve a zygote and therefore provide a chance for conception. Today, there are over 3 million offspring generated from ICSI throughout the world.
Refined treatment of men with severe oligozoospermia and various forms of azoospermia
The consistent pregnancies achieved with ICSI across the arrays of dysfunctional spermatozoa have allowed the possibility to push the boundaries of this technique towards the most extreme aspect of male infertility, when only few spermatozoa can be identified as often encountered in cryptozoospermia, virtual azoospermia or when surgical specimens are retrieved in cases of absolute azoospermia. The ability to obtain pregnancies with these scarce spermatozoa has introduced another variable: the injection of the non-ideal and unselected spermatozoon. My team as characterized these spermatozoa as euploid with a functional centrosome albeit with abnormal morphology. In subsequent follow-ups, we have found that cases performed with these spermatozoa have resulted in healthy children. My team has highlighted that utilization of such scarce and unselected spermatozoa can still yield rewarding pregnancy rates and reassuring offspring health.
Proof of the paternal inheritance of the human centrosome
The occurrence of severe chromosomal abnormalities in numerous embryos has been attributed to an abnormal mitotic spindle during syngamy related to centrosomal dysfunction. My team, through the genetic assessment of embryos generated from abnormally fertilized zygotes following in vitro fertilization and intra cytoplasmic sperm injection, was able to hypothesize and provide evidence of the paternal inheritance of the human centrosome. The centrosome has several implications for human infertility. It is possible that immotile or non-progressively motile spermatozoa may possess centriolar abnormalities or an absence of centrioles. Similarly, anti-sperm antibodies against centrioles may be responsible for mitotic arrest. One way of solving this problem would be the use of donor centrosomes. To this end, my research has assessed the ability of embryos injected with physically separated sperm segments (head only, head and tail separated or isolated tail) to develop normally. Fluorescent in situ hybridization revealed an almost universal mosaicism in these embryos, suggesting that physical disruption of the spermatozoa compromises the ability of the centrosome to function in the zygote.
Publications of interest:
1. Palermo G, Van Steirteghem A. Enhancement of acrosome reaction and subzonal insemination of a single spermatozoon in mouse eggs. Mol Reprod Dev 1991;30(4):339-45.
2. Palermo G, Joris H, Devroey P, Van Steirteghem AC. Induction of acrosome reaction in human spermatozoa used for subzonal insemination. Hum Reprod 1992;7(2):248-54.
3. Palermo GD, Avrech OM, Colombero LT, Wu H, Wolny YM, Fissore RA, Rosenwaks Z. Human sperm cytosolic factor triggers Ca2+ oscillations and overcomes activation failure of mammalian oocytes. Mol Hum Reprod 1997;3(4):367-74.
4. Lee B, Palermo G, Machaca K. Downregulation of store-operated Ca2+ entry during mammalian meiosis is required for the egg-to-embryo transition. J Cell Sci 2013;126(Pt 7):1672-81.