Fertility implication of paternally imprinted genes in Sertoli and Leydig cells : characterization, interaction and sensitivity to environmental insults

Abstract

The HPG axis interacts with the Sertoli and Leydig cells to ensure the proper functioning of the male reproductive system. Environmental insults, which are becoming increasingly more common, affect the sensitive male reproductive system in harmful ways. Therefore, the aim of this thesis was to, analyze a network of the paternally imprinted infertility genes shared between the HPG axis and the Sertoli and Leydig cells. With this network in place, we aimed to develop a cell culture system that would allow the evaluation of the effects of certain environmental contaminants such as mycotoxins on Sertoli and Leydig cells. Results showed that 27 paternally imprinted genes were commonly expressed in Sertoli, Leydig cells, and the HPG axis, while 65 genes were present in both Sertoli and Leydig cells, only 1 in both Leydig cells and HPG and 1 common between Sertoli cells and HPG. Moreover, 42 genes were found to be expressed only in the Sertoli cell, 30 only in the Leydig cell, and 5 only in the HPG axis. Then, several networks with each of these groups of genes was constructed, and a Venn diagram showing the commonalities and uniqueness of these genes was constructed. The cell culture system developed was composed of a mechanical digestion step where testicular tissue was minced followed by enzymatic digestion with collagenase or trypsin. Unfortunately, the Sertoli and Leydig cell culture system could not be maintained in culture, possibly because of such factors as stress associated with digestion conditions, inappropriate incubation temperature, and little information to base the culture protocol on. The bioinformatics analysis of the paternally imprinted infertility genes paves the way for new avenues in discussing infertility and the interplay between Sertoli, Leydig cells and the HPG axis.