Association of Y chromosome AZF region microdeletions with recurrent miscarriage in Iranian couples: A case-control study

Mol Genet Genomic Med. 2024 Feb;12(2):e2392. doi: 10.1002/mgg3.2392.

Abstract

Background: Recent studies have linked recurrent pregnancy loss (RPL) to abnormalities in the sperm genome, specifically microdeletions in the azoospermia factor (AZF) region. This study investigated the potential association between Y chromosome microdeletions in the AZF region and RPL in Iranian couples.

Methods: The research presents a case-control study of 240 men: 120 whose partners experienced recurrent miscarriage, and 120 who had successful pregnancies without history of miscarriage. The study used semen parameters, hormone analyses, and microdeletion analysis via multiplex PCR and the YChromStrip kit. Thus, the sequence-tagged site (STS) markers of AZFa (sY84, sY86), AZFb (sY127, sY134), and AZFc (sY254, sY255) regions were examined.

Results: The variations in semen parameters and sex hormone levels between cases and controls are suggest impaired testicular function in men whose partners had recurrent miscarriages (p < 0.05). Furthermore, the study revealed a negative correlation between sperm count and follicle-stimulating hormone (FSH) level, and a positive one between sperm motility and testosterone concentration. There were no microdeletions in the control group, while the RPL group showed 20 deletions in AZFb (sY134) (16.66%) and 10 deletions each in AZFb (sY127) (8.33%) and AZFc (sY254) (8.33%).

Conclusion: Microdeletions in sY134 (AZFb) were significantly associated with RPL in Iranian men (p = 0.03). AZF microdeletion screening in couples with RPL can provide valuable information for ethnical genetic counseling and management of recurrent miscarriage. Further studies on larger populations or across various ethnic groups, conclusions and the inclusion of other factors like epigenetic changes explain the role of AZF microdeletions in RPL.

Keywords: azoospermia; microdeletions; multiplex PCR; recurrent miscarriage.

MeSH terms

  • Abortion, Habitual* / genetics
  • Case-Control Studies
  • Chromosome Deletion*
  • Chromosomes, Human, Y
  • Female
  • Humans
  • Infertility, Male*
  • Iran
  • Male
  • Pregnancy
  • Semen*
  • Sex Chromosome Aberrations*
  • Sex Chromosome Disorders of Sex Development*
  • Sperm Motility
  • Y Chromosome

Supplementary concepts

  • Male sterility due to Y-chromosome deletions