Disease relevance of Oligospermia

• To ascertain if androgen insensitivity causes severe oligospermia or azoospermia we studied three unrelated, phenotypically normal men with long histories of infertility [1].
• CONTEXT: Infertile men with obstructive azoospermia may have mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, many of which are rare in classic cystic fibrosis and not evaluated in most routine mutation screening [2].
• Mice that are nullizygous for Sbf1 exhibit male infertility characterized by azoospermia [3].
• In hyperprolactinemia associated with galactorrhea, amenorrhea, oligospermia, and impotence, bromocriptine reduces prolactin levels to normal and allows for satisfactory return of sexual and reproductive function in 90% of patients [4].
• Sperm analysis of 21 patients taking sulphasalazine for inflammatory bowel disease revealed that 86% had abnormal semen analysis and 72% had oligospermia [5].

Psychiatry related information on Oligospermia

• Two athletes with severe oligospermia were found to have the lowest values of T and FT and significant differences in psychologic stress scores [6].

High impact information on Oligospermia

• BACKGROUND: Some infertile men with azoospermia or severe oligospermia have small deletions in regions of the Y chromosome [7].
• Loss of boule function results in azoospermia; meiotic divisions are blocked, although limited spermatid differentiation occurs [8].
• A candidate gene for the Y-chromosome azoospermia factor (AZF) has been identified and named Deleted in Azoospermia (DAZ) [8].
• Such agents can affect fertility and other aspects of male reproductive function, for example, treatment with anti-cancer drugs such as cyclophosphamide has been associated with oligozoospermia, azoospermia and increased levels of serum follicle-stimulating hormone (FSH) [9].
• Such deletions determine azoospermia more frequently than severe oligozoospermia and involve especially the AZFc region including the DAZ gene family [10].

Chemical compound and disease context of Oligospermia

• Reversible azoospermia induced by the anabolic steroid 19-nortestosterone [11].
• The suspected cause was exposure to the chemical 1,2-dibromo-3-chloropropane (D.B.C.P.). The major effects, seen in 14 of 25 non-vasectomised men, were azoospermia or oligospermia and raised serum-levels of follicle-stimulating hormone and luteinising hormone [12].
• Azoospermia induced by 19-nortestosterone [13].
• In some male patients with findings characteristic of cystic fibrosis, but normal sweat chloride concentrations, the demonstration of obstruction azoospermia has been pivotal in diagnosis [14].
• Although exogenous T or T plus progestin treatments efficiently block gonadotropin secretion and suppress testicular T production, only approximately 60% of treated Caucasian men reach contraceptive azoospermia [15].

Biological context of Oligospermia

• Three different spermatogenesis loci have been mapped on the Y chromosome and named "azoospermia factors" (AZFa, b, and c) [10].
• The Drosophila boule gene is expressed exclusively in the male germline and encodes an RNA binding protein closely related to the mammalian fertility factors encoded by the DAZ (Deleted in Azoospermia) and DAZL (DAZ-like) genes [16].
• These results suggested that neither genetic polymorphisms in the AR gene (CAG and GGC repeats) nor that in hepatic androgen metabolism (CYP3A4 A/G variant) were the major contributors to the within-population variations in susceptibility to T-induced azoospermia [17].
• A phenotypically normal male with azoospermia was found to have a translocation between the short arm of the Y chromosome and the distal long arm of a chromosome 4 [18].
• Progressive dose-dependent testicular atrophy and oligospermia occurred at low and intermediate dosages of doxorubicin (0.1 to 5 mg./kg.). Marked testicular atrophy, oligospermia and germinal aplasia were observed at high dosage of doxorubicin (10 mg./kg.). LD50 for animal mortality at day 56 +/- 2 for doxorubicin appears to be 10 mg./kg [19].

Anatomical context of Oligospermia

• Mean seminal plasma clusterin concentrations were significantly lower in azoospermia caused by obstruction or seminiferous tubule failure than with oligospermia or normospermia [20].
• Mutations in MTMR2, the myotubularin-related 2 gene, cause autosomal recessive Charcot-Marie-Tooth (CMT) type 4B1, a demyelinating neuropathy with myelin outfolding and azoospermia [21].
• The Deleted in AZoospermia (DAZ) genes encode potential RNA-binding proteins that are expressed exclusively in prenatal and postnatal germ cells and are strong candidates for human fertility factors [22].
• Its role in spermatogenesis is supported by its exclusive expression in testis, its deletion in a high percentage of males with azoospermia or severe oligospermia, and its homology with a Drosophila male infertility gene boule [23].
• In fibroblasts from 1 to 4 individuals with severe oligospermia of unknown cause (less than 1 million/ml) and 8 of 18 subjects with idiopathic azoospermia, the androgen receptor Bmax was less than 12 fmol/mg protein [24].

Gene context of Oligospermia

• We investigated the function of DDX3Y, the Y chromosome AZFa region encoding a putative DEAD-box RNA helicase protein, the loss of which results in oligozoospermia or azoospermia in humans [25].
• Y-chromosomal DAZ (deleted in azoospermia) and autosomal DAZ-like (DAZL) comprise a gene family involved in gametogenesis [26].
• HLA-DR antigen and HLA-DRB1 genotyping with nonobstructive azoospermia in Japan [27].
• RESULT(s): All 12 biopsy specimens from patients with obstructive azoospermia were positive for telomerase activity, hTR, and hTERT [28].
• The concentration of S-Tf-R in post-vasectomy samples was lower than that in patients with azoospermia of primary testicular origin (P < 0.05; positive likelihood ration = 7 at value of 8.3 IU/ ml) [29].

Analytical, diagnostic and therapeutic context of Oligospermia

• Extrapolated to humans, it may indicate that only total abolition of testicular androgen action will result in consistent azoospermia, which is necessary for effective male contraception [15].
• Recently, multicenter clinical trials to determine male contraceptive efficacy disclosed that testosterone-induced suppression of spermatogenesis to azoospermia occurred in about 90% of Asian but only 60-70% of white men [30].
• Using fluorescent in situ hybridization, we located DYZ4 and DYZ3 on chromosome 11qter and concluded that a de novo translocation (Y;11) (q11.2;q24) with a deletion of 11q24----qter and a deletion of Yq11.2----Yqter were present; Jacobsen syndrome and azoospermia are associated with these deletions [31].
• Use of electively cryopreserved microsurgically aspirated epididymal sperm with IVF and intracytoplasmic sperm injection for obstructive azoospermia [32].
• Increased sperm count in 25 cases of idiopathic normogonadotropic oligospermia following treatment with tamoxifen [33].

References