Mutational analysis of the human FATE gene in 144 infertile men

Abstract

The FATE gene maps to Xq28 where one case of a translocation breakpoint has been found in an infertile man. Moreover, the FATE promoter contains a putative SF-1-binding site, and FATE has been proposed as representing a target gene of SF-1 in testicular development or germ cell differentiation. This study presents a complete mutational screening of the FATE gene in a random group of 144 infertile males. Four polymorphisms and two mutations were found. Three of the polymorphisms, viz., 741C-->T, 905A-->C, and 3985C-->T, occurred in exon 5 and intron 2 and did not alter the deduced polypeptide. One polymorphism resulted in the conservative amino acid exchange, A10 V, in 16.0% of the patients. This substitution occurred with similar frequencies in the control groups, indicating that the mutation does not affect fertility in men or women. The two mutations caused the non-conservative amino acid substitutions S125R (patient 1) and I34T (patient 2). A family study (patient 1) revealed, however, that S125R was inherited and that a fertile male family member carried the mutation. Patient 2 did not have relevant family members who could be examined. Thus, this study has shown that only 1.4% of infertile men have mutations in the FATE gene, and that some of these mutations do not singly cause infertility. Hence, FATE may not play an important role in the disease-state of infertile men attending fertility clinics. However, FATE mutations cannot be excluded as being a contributing factor in some cases of male infertility.

Single-Cell RNA Sequencing Analysis Reveals Sequential Cell Fate Transition during Human Spermatogenesis

“…In detail, we have identified several interesting DEGs in Sertoli cells ( including INHA, BEX1, GSTA1, DEFB119, and FATE1) and MIX (including CD63, TIMP1, PTGDS, and INSL3) from this NOA patient as compared with those in donors with normal spermatogenesis (Figures 7E and 7F). Many of these genes were potentially associated with male reproduction (Olesen et al, 2003;Yang et al, 2002). And GO terms, such as ''response to oxidative stress'' and ''DNA damage response,'' were enriched in the upregulated genes of the testicular somatic cells from this NOA patient ( Figure 7G).…”

Mitochondrial dynamics during spermatogenesis

“…There is no evidence that MFF or other mitochondrial fission factors are important for male fertility in humans. Fetal and adult testis-expressed 1 (FATE1) is a testis-specific protein with some sequence similarity to MFF (Olesen et al, 2001), but its role in human fertility remains inconclusive (Olesen et al, 2003).…”

The X chromosome and male infertility

“…FATE1 belongs to the CTA family, and in 2003 it was sequenced in a cohort of 144 randomly selected infertile patients (Olesen et al 2003). The authors reported two missense variants in two unrelated asthenozoospermic men.…”