Date Published: February 11, 2019
Publisher: Public Library of Science
Author(s): Georges Raad, Joseph Azouri, Kamal Rizk, Nina S. Zeidan, Jessica Azouri, Valérie Grandjean, Mira Hazzouri, Joël R. Drevet.
Growing evidence suggests that paternal obesity may decrease male fertility potential. During infertility treatment with intra-cytoplasmic sperm injection (ICSI), a morphologically normal motile spermatozoon is injected into a mature egg, when possible. However, sperm motility and morphology per se do not reflect the sperm molecular composition. In this study, we aimed to assess the quality of motile spermatozoa in the context of obesity by analysing their conventional and molecular characteristics as well as their ability to promote early embryonic development. A prospective study was conducted on 128 infertile men divided into three groups: 40 lean, 42 overweight, and 46 obese men. Conventional sperm parameters (concentration, motility and morphology) and sperm molecular status (chromatin composition and integrity, 5-methycytosine (5-mC) and 5-hydroxycytosine (5-hmC) contents and oxidative stress level) were analysed on raw semen and/or on motile spermatozoa selected by density gradient or swim-up techniques. Morphokinetic analysis of the embryos derived from ICSI was performed using the Embryoviewer software. Our results showed that the motile sperm-enriched fraction from obese men exhibited higher levels of retained histones (p<0.001), elevated percentage of altered chromatin integrity (p<0.001), and decreased contents of 5-hmC (p<0.001), and 5-mC (p<0.05) levels as compared to that from lean men. Importantly, there were no statistically significant correlations between these molecular parameters and the percentages of morphologically normal motile spermatozoa. Regarding embryo morphokinetics, the CC1 (p<0.05) and CC3 (p<0.05) embryonic cell cycles were significantly delayed in the cleavage embryos of the obese group as compared to the embryos of the lean group. Our data is of particular interest because, besides demonstrating the negative impacts of obesity on motile spermatozoa molecular composition, it also highlights the possible risk of disturbing early embryonic cell cycles kinetics in the context of paternal obesity.
Obesity, as defined by excessive accumulation of adipose tissue, is a worldwide public health crisis [1–4]. It is one of the risk factors leading to the development of several pathologies, such as type 2 diabetes mellitus (T2DM), cardiovascular diseases, respiratory diseases and hypertension [5, 6]. Furthermore, several studies have documented the possible association between paternal obesity and male infertility [7, 8]. This is especially alarming given the high prevalence of obesity among young men of reproductive age [9, 10].
Our work showed that paternal obesity (as measured by BMI and WC) is associated with alterations in the molecular composition of the motile sperm-enriched fraction as well as in pre-implantation embryo morphokinetics.
Our data indicate that male obesity is associated with various epigenetic modifications in the motile sperm and with distinct morphokinetic changes in the preimplantation embryos. Further studies are needed to validate on one hand whether a high BMI-induced sperm epigenetic signature modifications are associated with abnormal embryonic development, and on another hand whether embryo morphokinetics alterations cause long-term health hazards on neonates. Considering the interplay between obesity, molecular sperm quality and embryonic development, our data suggest that the time-lapse imaging technology might be considered in a future as an important tool enabling a better selection embryo in the context of pathologies known to alter the sperm quality.