I. INTRODUCTION TO REPRODUCTIVE GENETICS
Reproductive genetics studies genetic factors that affect:
- fertility in males and females,
- embryonic and fetal viability,
- pregnancy maintenance and outcome.
Infertility and pregnancy loss often result from chromosomal abnormalities, single-gene disorders, or complex genetic–environmental interactions.
Definitions
- Infertility: failure to achieve pregnancy after 12 months of regular unprotected intercourse.
- Primary infertility: no prior pregnancies.
- Secondary infertility: infertility after a previous pregnancy.
- Spontaneous pregnancy loss (miscarriage): loss before 20–22 weeks of gestation.
- Stillbirth: fetal death after 20–22 weeks (definitions may vary by country).
II. GENETIC CAUSES OF MALE INFERTILITY
Genetic causes account for a significant proportion of severe male factor infertility, especially in:
- azoospermia,
- severe oligozoospermia,
- abnormal spermatogenesis.
A. Chromosomal Abnormalities
Numerical Abnormalities
- Klinefelter syndrome (47,XXY)
- Most common chromosomal cause of male infertility
- Testicular failure → azoospermia
Structural Abnormalities
- Balanced translocations
- Inversions
Effect:
- Abnormal meiosis
- Production of genetically unbalanced sperm
- Infertility or recurrent pregnancy loss in partner
B. Y Chromosome Microdeletions
AZF Region Deletions
- Located on Yq11
- Regions: AZFa, AZFb, AZFc
Pathogenesis
- Deletion of genes required for spermatogenesis.
- Arrest of sperm production at different stages.
- Severity depends on deleted region.
Clinical Correlation
- AZFa → Sertoli cell–only syndrome
- AZFb → spermatogenic arrest
- AZFc → variable oligozoospermia or azoospermia
C. Monogenic Disorders
CFTR Gene Mutations
- Cause congenital bilateral absence of the vas deferens (CBAVD)
- Sperm production normal, but transport absent
Other Genetic Causes
- Mutations affecting hormone receptors
- Disorders of sex development (DSD)