Y chromosome microdeletions in infertile Moroccan males: 10 years laboratory experience in AZF deletions

Genetic causes of male infertility are abnormalities in chromosome numbers and/or structures, Y-chromosome deletions and gene mutations. Genetic screening of male infertility is rarely done in our country. The purpose of the study was to investigate the frequencies and types of Y chromosome microdeletions in infertile men, based on studies done in the Human Genetics Laboratory of the Pasteur Institute in Morocco.A total of 543 infertile men were screened for Y chromosome microdeletions.The prevalence of AZF Y-chromosome microdeletions among infertile men range from 3% to 10% depending on patients selected. The most frequent microdeletions were detected in the AZFc region, followed by AZFbc, AZFb, AZFa, AZFab.These results indicate the need for Y chromosome microdeletion screening for better management of infertile patients.We hope to encourage use of genetic diagnosis and also research in this field to initiate collaboration for clinical management and appropriate genetic diagnosis and counselling for male infertility

Relaxin-like peptides in male reproduction: a human perspective

The relaxin family of peptide hormones and their cognate GPCRs are becoming physiologically well-characterized in the cardiovascular system and particularly in female reproductive processes. Much less is known about the physiology and pharmacology of these peptides in male reproduction, particularly as regards humans. H2-relaxin is involved in prostate function and growth, while insulin-like peptide 3 (INSL3) is a major product of the testicular Leydig cells and, in the adult, appears to modulate steroidogenesis and germ cell survival. In the fetus, INSL3 is a key hormone expressed shortly after sex determination and is responsible for the first transabdominal phase of testicular descent. Importantly, INSL3 is becoming a very useful constitutive biomarker reflecting both fetal and post-natal development. Nothing is known about roles for INSL4 in male reproduction and only very little about relaxin-3, which is mostly considered as a brain peptide, or INSL5. The former is expressed at very low levels in the testes, but has no known physiology there, whereas the INSL5 knockout mouse does exhibit a testicular phenotype with mild effects on spermatogenesis,probably due to a disruption of glucose homeostasis. INSL6 is a major product of male germ cells, although it is relatively unexplored with regard to its physiology or pharmacology, except that in mice disruption of the INSL6 gene leads to a disruption of spermatogenesis. Clinically, relaxin analogues may be useful in the control of prostate cancer, and both relaxin and INSL3 have been considered as sperm adjuvants for in vitro fertilization

Association of Spermatogenic Failure with the b2/b3 Partial AZFc Deletion

Infertility affects around 1 in 10 men and in most cases the cause is unknown. The Y chromosome plays an important role in spermatogenesis and specific deletions of this chromosome, the AZF deletions, are associated with spermatogenic failure. Recently partial AZF deletions have been described but their association with spermatogenic failure is unclear. Here we screened a total of 339 men with idiopathic spermatogenic failure, and 256 normozoospermic ancestry-matched men for chromosome microdeletions including AZFa, AZFb, AZFc, and the AZFc partial deletions (gr/gr, b1/b3 and b2/b3)

Association of the MTHFR A1298C Variant with Unexplained Severe Male Infertility

The methylenetetrahydrofolate reductase (MTHFR) gene is one of the main regulatory enzymes involved in folate metabolism, DNA synthesis and remethylation reactions. The influence of MTHFR variants on male infertility is not completely understood. The objective of this study was to analyze the distribution of the MTHFR C677T and A1298C variants using PCR-Restriction Fragment Length Polymorphism (RFLP) in a case group consisting of 344 men with unexplained reduced sperm counts compared to 617 ancestry-matched fertile or normozoospermic controls. The Chi square test was used to analyze the genotype distributions of MTHFR polymorphisms. Our data indicated a lack of association of the C677T variant with infertility. However, the homozygous (C/C) A1298C polymorphism of the MTHFR gene was present at a statistically high significance in severe oligozoospermia group compared with controls (OR = 3.372, 95% confidence interval CI = 1.27–8.238; p = 0.01431). The genotype distribution of the A1298C variants showed significant deviation from the expected Hardy-Weinberg equilibrium, suggesting that purifying selection may be acting on the 1298CC genotype. Further studies are necessary to determine the influence of the environment, especially the consumption of diet folate on sperm counts of men with different MTHFR variants

Sun exposure, dressing habits, and vitamin D status in Morocco

Sunlight is the main source of vitamin D. Almost 80% of vitamin D3 is produced in the skin. The region of Draa Tafilalet benefits from long daily sunshine time. As such, vitamin D deficiency should be low in this region. However, dressing habits can highly influence vitamin D status. This study aimed to evaluate sun exposure and its relation to vitamin D status among the general population in the region of Draa-Tafilalet, Morocco. Clinical, biological, and sociodemographic data were obtained from 331 adults visiting local healthcare units during the summers of 2019 and 2020. Plasma 25(OH)D2/D3 was measured by immunofluorescence. The prevalence of vitamin D deficiency was 37.5%, while Vitamin D insufficiency represented 56.5%. Most of the studied population (76.4%) had restricting dressing habits and exposed only their faces. statistic tests showed a correlation of vitamin D levels with daily sun exposure (r= 0.308, p<0.001), dressing habits (p<0.001), age (r= -0.141, p=0.01), sex (p<0.001), physical activity level (p=0.003), and BMI (r= -0.298, p<0.001). The study showed a high prevalence of vitamin D deficiency in this region. Similarly, it exposed the effects of restricting clothes and low daily sun exposure on vitamin D status

Mutations in the protamine locus: association with spermatogenic failure?

abstract: The protamine locus consists of a 28.5 kb region with a linear array of the protamine (PRM)1, PRM2, PRM3 and transition nuclear protein (TNP)2 genes. Several studies indicate an abnormal expression pattern of protamine genes associated with male infertility, although the molecular mechanism underlying this observation is unclear. Here, we determined the spectrum of DNA variants present in all four genes in men with unexplained infertility compared with an ancestry-matched fertile/normospermic population. A total of 160 control individuals and at least 125 infertile men with either idiopathic azoospermia or oligozoospermia were sequenced for the open reading frame of PRM1, PRM2, PRM3 and TNP2 genes. All individuals carried an apparently intact Y chromosome. Of the 28 variants identified, 21 were previously described in the literature. The novel variants that were observed only in the infertile cohort included the SNP c.65G.A mutation which resulted in an amino acid change at the codon 22 (p.Ser22Asn) in the PRM1 gene, a mutation in the promoter region of PRM2 (267C.T) and a nonsense mutation in the PRM3 gene. These data are consistent with that of previous studies which have indicated that mutations in the protamine locus may be an infrequent cause of male infertility

Y-chromosome AZFc structural architecture and relationship to male fertility

International audienceObjective: To determine if there is a relationship between various forms of partial AZFc deletions and spermatogenic failure.Design: Case-control study.Setting: Infertility clinic (Tenon Hospital, Paris).Patient(s): 557 men, comprising 364 infertile men from mixed ethnic backgrounds, and 193 men with known fertility (n = 84) and/or normospermic (n = 109).Intervention(s): Characterization of 32 partial AZFc deletions.Main outcome measure(s): DAZ gene cluster divided into two families (DAZ1/2 and DAZ3/4), CDY1 gene, and Y-chromosome haplogroups.Result(s): We observed 18 partial AZFc deletions in 364 (4.95%) infertile men compared with 14 out of 193 (7.25%) in the control normospermic/fertile group.Conclusion(s): The analysis of informative Y-chromosome single nucleotide variants combined with Y-chromosome haplogroup definition enabled us to infer seven deletion classes that occur on a minimum of six Y-chromosome parental architectures. We found no relationship between either the presence or the absence of DAZ1/2, DAZ3/4, CDY1a, or CDY1b with spermatogenic failure at least on one Y-chromosome lineage. The DAZ dosage and Southern blot analyses indicated that the majority of individuals tested carried two copies of the DAZ gene, indicating a partial AZFc deletion. Our data are consistent with the hypothesis that, at least in our study populations, partial AZFc deletions may have a limited impact on fertility