Role In Human Infertility Research Articles

Spermatogonial depletion and a spermatogenesis defect in the Dp(16)1Yey mouse model of Down syndrome

In brief Little is known about the mechanism responsible for male infertility in Down syndrome. Duplication of Mmu16 chromosome (an orthologue of Hsa21, bearing Dyrk1A) in Dp(16)1Yey mice is responsible for impaired spermatogenesis through spermatogonial depletion and hypogonadotropic hypogonadism. Abstract Down syndrome (DS), or trisomy 21, is the most common chromosomal disorder in humans. Men with DS are infertile. The DYRK1A gene on Hsa21 is involved in several features of DS. Overexpression of the homolog dyrk1A disrupts primordial germ cell migration in zebrafish, and overexpression of Dyrk1A impairs gonadotropic axis function and the early stages of spermatogenesis in the mouse. Other genes on Hsa21 might be involved in the pathogenesis of infertility in DS. We investigated the Dp(16)1Yey mouse model of DS, which features segmental duplication of chromosome Mmu16 (orthologous to a large part of Hsa21 and carrying Dyrk1A and 112 other genes). Using an immunohistochemical assay for the spermatogonial marker STRA8, we observed spermatogonial depletion in the Dp(16)1Yey mouse. This was correlated with low mRNA expression of GFRα1 (a marker of the self-renewal stem cell pool) in an RT-qPCR assay and low protein expression of PLZF (a marker of differentiating stem cells) in a slot-blot assay. Spermatogenesis was present but impaired, with a low sperm count, low protamine-1 expression, a low testis weight, and a low seminiferous tubule diameter. Low circulating luteinizing hormone and follicle-stimulating hormone levels and an elevated testis anti-Müllerian hormone level (as measured in ELISAs) revealed the presence of hypogonadotropic hypogonadism. The Dp(16)1Yey mouse model of DS recapitulates observations made in zebrafish and mice overexpressing DYRK1A homologs. The presence of an excess of Mmu16 material perturbs spermatogenesis and the gonadotropic axis. More generally, DYRK1A’s role in human infertility (outside DS) remains to be characterized.

Zearalenone, an abandoned mycoestrogen toxin, and its possible role in human infertility.

This is a Letter to the Editor and does not have an abstract. Please download the PDF or view the article HTML.

Improvement of laboratory diagnostics of urogenital chlamydial infection in patients with impaired reproductive functions found to be infected with Chlamydia trachomatis

The dominant role in human infertility has been attributed to sexually transmitted infections (STIs) with a leading contribution of urogenital chlamydial infection (UGCI) caused by Chlamydia trachomatis (CT). the two variants of this pathogen are represented by the wild-type (wtCT) and new Swedish (nvCT) strains containing 377 bp deletion within the cryptic plasmid orf1 gene. Objective. The purpose of the study was investigation of the clinical specimens obtained from the urogenital tract of couples coping with infertility for the presence of genetic material of wtCT and nvCT. Material and methods. Clinical samples (scrapings from the urethra and cervix) obtained from 25 to 41 years old couples (n = 14) were tested for the presence of identifiable wtCT and nvCT chlamydia DNA by monoplex and duplex PCR, specific antigens C. trachomatis in elementary bodies by using immunofluorescence analysis (IFA), while detection of anti-chlamydia antibodies in sera was determined by immunoenzymatic assay (IEA). Results. The nvCT variant with typical deletion of 377 bp within the orf1 gene that belongs to the genovar e subtype E1 was detected in 100% of couples with infertility. The negative results of DNA testing for wtcT were registered in 87.5% of patients from this group, while one individual (12.5%) was likely coinfected with nvCT and wtCT of E1 and D genovars, respectively. The wtCT strains of genovar E (subtypes E1, E2, E6), g (subtypes G1, G2), F (subtypes F1), and K were identified in control group among patients with UGCI. The study revealed difficulties in detection of nvCT by nucleic acid amplification test (NAAT), IFA, and IEA; data on comparison of the efficacy of these methods are presented. Conclusion. Chronic UGCI in patients with reproductive dysfunctions can be caused by nvCT alone or as result of co-infection with nvCT and wtCT. The negative results in NAAT may not 100% correlate with the absence of UGCI that requires further confirmation in tests allowing detection of all known variants of C. trachomatis.

Trichomonas vaginalis: pathogenicity and potential role in human reproductive failure.

Trichomonas vaginalis, which colonizes the genitourinary tract of men and women, is a sexually transmitted parasite causing symptomatic or asymptomatic trichomoniasis. The host-parasite relationship is very complex, and clinical symptoms cannot likely be attributed to a single pathogenic effect. Among the many factors responsible for interactions between T. vaginalis and host tissues, contact-dependent and contact-independent mechanisms are important in pathogenicity, as is the immune response. This review focuses on the potential virulence properties of T. vaginalis and its role in female and male infertility. It highlights the association between T. vaginalis infection and serious adverse health consequences experienced by women, including infertility, preterm birth and low-birth-weight infants. Long-term clinical observations and results of in vitro experimental studies indicate that in men, trichomoniasis has been also associated with infertility through inflammatory damage to the genitourinary tract or interference with sperm function. These results contribute significantly to improving our knowledge of the role of parasitic virulence factors in the development of infection and its role in human infertility.

Clastogenic effects of different Ureaplasma urealyticum serovars on human chromosomes.

The possibility that Ureaplasma urealyticum might play an important role in human infertility was first raised more than 20 years ago, but this association remains speculative. Considering the hypothesis that the pathogenicity of Ureaplasma urealyticum may depend on its serotypes, the clastogenic effects of different strains of Ureaplasma urealyticum, at concentrations of 10(3) CCU (color changing units)/ml, 10(4) CCU/ml and 10(5) CCU/ml, were evaluated in vitro in short-term cultures of human lymphocytes. Total or partial mitotic inhibition was produced by Ureaplasma urealyticum serotypes 2, 3 and 10 independent of the concentration (10(3) CCU/ml, 10(4) CCU/ml or 10(5) CCU/ml) of the microorganisms employed. In contrast, the clastogenic effects observed with serotypes 1, 7 and 12 varied according to the concentration employed in the test. Mitotic alterations were observed in Ureaplasma urealyticum serotypes 5, 6, 7, 8, 9, 11 and 12. Chromatid gaps (53.0%) and chromatid breaks (13.9%) were the most frequent types of alterations observed. The results of this in vitro assay demonstrated that the clastogenic effects varied with the Ureaplasma urealyticum serotypes evaluated.

Uterine Receptivity

Reduced uterine receptivity can play a major role in human infertility, particularly following ovarian stimulation as occurs during ovulation induction and IVF. Many of the conventional histological and morphological markers used to identify normal progestational changes in the human uterus are inadequate as markers of uterine receptivity for implantation, and new techniques including ultrasound and morphometric measurement will be required. At the same time, a'better understanding of the cellular processes involved in human implantation is required if we are to identify markers of uterine receptivity. Recent observations suggest that the uterus is normally a barrier to embryo implantation and that uterine receptivity is in fact the loss of this barrier function, rather than the acquisition of new structural or functional capabilities.