Clinical studies of human Xlinked genes and infertility

Few studies have examined mutations in X-linked genes in male infertility patients (Table 10.4). In a study of 56 infertile men with low or no sperm counts, Raverot et al. observed mutations in the SOX3 gene (sex-determining region Y box 3) (Raverot et al., 2004). The mouse homolog of this gene is found in the developing gonad and brain and, when disrupted, causes hypogonadism with loss of germ cells. Mutations in the human fetal and adult testis-expressed (FATE) gene (Xp28) have also been studied in infertile men (Olesen et al., 2003). This gene encodes a polypeptide of 21kDa that is not related to any known proteins. The FATE message is testis specific in fetal life soon after sex-determination and is co-expressed with SRY in the 7-week-old testis. Among 144 random chosen infertile men and 100 proven fertile men, a study of the FATE gene revealed 6 nucleotide substitutions, 4 of which were not amino acid altering, and 2 mutations. Each mutation was found only once in the experimental group, and neither was found in the controls. Neither affected patient had a karyotype abnormality nor a Y chromosome microdeletion. However, in one affected patient, a maternal uncle also carried the mutation and was fertile. The authors concluded that FATE gene mutations may be contributory but not necessarily common or important causes of male infertility.

There is also speculation that the ZFX gene in humans, a zinc finger protein located on the X chromosome that appears to be a transcriptional activator, may function in sex differentiation or spermatogenesis (Mardon and Page, 1989). To study this hypothesis, Luoh et al. used a reverse genetic strategy, mutagenized the mouse homolog ZFX and noted organismal effects that might suggest a role of this gene in reproductive development or function (Luoh et al., 1997). The ZFX mutant had an impressive decrease in primordial germ cell number during the embryonic period before testicular differentiation. After birth, the mutant mice were smaller, had smaller testes and epididymides, and had sperm counts reduced by one half compared to wild type mice.

Pregnancy Guide

Pregnancy Guide

A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.

Get My Free Ebook


Post a comment