Coordinated transcriptional regulation patterns associated with infertility phenotypes in men

Abstract

Introduction: Microarray gene-expression profiling is a powerful tool for global analysis of the transcriptional consequences of disease phenotypes. Understanding the genetic correlates of particular pathological states is important for more accurate diagnosis and screening of patients, and thus for suggesting appropriate avenues of treatment. As yet, there has been little research describing gene-expression profiling of infertile and subfertile men, and thus the underlying transcriptional events involved in loss of spermatogenesis remain unclear. Here we present the results of an initial screen of 33 patients with differing spermatogenic phenotypes. Methods: Oligonucleotide array expression profiling was performed on testis biopsies for 33 patients presenting for testicular sperm extraction. Significantly regulated genes were selected using a mixed model analysis of variance. Principle components analysis and hierarchical clustering were used to interpret the resulting dataset with reference to the patient history, clinical findings and histological composition of the biopsies. Results: Striking patterns of coordinated gene expression were found. The most significant contains multiple germ cell-specific genes and corresponds to the degree of successful spermatogenesis in each patient, whereas a second pattern corresponds to inflammatory activity within the testis. Smaller-scale patterns were also observed, relating to unique features of the individual biopsies.

Semen analysis: update on clinical value, current needs and future perspectives

“…A different approach, focussing on the RAS oncogene RAP1A as a possible specific marker for fertility (Yang et al 2004), found that although mRNA expression was higher in azoospermic compared with normozoospermic patients, this was accompanied by variations in 127 other genes. A similar outcome was reported by Ellis et al (2007) in different human infertility phenotypes, namely distinct expression patterns, some germ cell-specific, but large variations in numerous genes of 'unknown' function. (A partial list of identified genes shown to have some relevance to male reproductive function is provided in Supplementary Table 1, see section on supplementary data given at the end of this article.…”

Altered gene expression signature of early stages of the germ line supports the pre‐meiotic origin of human spermatogenic failure

“…Some recent microarray studies have assessed global gene expression analysis in testicular biopsies from infertile men to identify the genes critical for spermatogenesis (Fox et al, 2003;Rockett et al, 2004;Ellis et al, 2007;Feig et al, 2007;von Kopylow et al, 2010;Chalmel et al, 2012). In these studies specific germ cell transcription patterns are inferred from infertile testicular phenotypes in men and a pattern of significantly decreased regulated genes has been attributed to the degree of spermatogenic failure and the loss of specific stages of germ cells.…”

The genetic causes of male factor infertility: A review

“…Genomic analysis can also be used to determine differentially transcribed genes (157). An enhanced understanding of transcription regulation could help geneticists discover how different expression patterns impact a patient's fertility (155). Additionally, microarrays can be used to study the effect of hormones or growth factors on gene expression profiles.…”

“…Microarrays are valuable tools for the identification of gene expression profiles of infertile phenotypes (155). Examining the simultaneous expression of genes allows geneticists to determine molecular signatures related to infertile phenotypes (156).…”