İnfertilitenin Genetik Nedenleri
Özet
İnfertilite, erkek ve kadın faktörlerinin yanı sıra idiyopatik nedenlerden de kaynaklanan, genetik ve genomik kusurların önemli rol oynadığı karmaşık bir hastalıktır. Genetik anomaliler; kromozomal sayısal ve yapısal kusurlar, tek gen mutasyonları ve epigenetik düzensizlikler yoluyla spermatogenez ile oogenezi bozarak kısırlığa yol açar. Erkek infertilitesinde azospermi hastaları en yüksek genetik risk grubundadır; Klinefelter sendromu, 46,XX erkek sendromu, 47,XYY sendromu, Y kromozomu mikrodelesyonları (AZF) ve CFTR mutasyonları gibi faktörler öne çıkar. Kadın infertilitesinde ise ileri anne yaşına bağlı anöploidiler, Turner sendromu, trizomi X, Swyer sendromu gibi gonadal diseneziler ve X-kromozomu yapısal düzenlenmeleri etkilidir. Ayrıca endometriozis, polikistik over sendromu (PCOS) ve erken over yetmezliği (POI) gibi durumların da belirgin genetik ve ailesel temelleri bulunmaktadır. Yeni nesil dizileme (NGS) gibi yüksek çözünürlüklü teknikler bu kusurların tanımlanmasını kolaylaştırarak yardımcı üreme teknolojilerinde (ART) üreme ve çocuk sağlığı açısından kritik prognostik değer sunmaktadır.
Infertility is a complex disease arising from male, female, or idiopathic factors, where genetic and genomic defects play a significant role. Genetic abnormalities cause infertility by disrupting spermatogenesis and oogenesis through chromosomal numerical and structural defects, single-gene mutations, and epigenetic irregularities. In male infertility, patients with azoospermia carry the highest genetic risk, with prominent factors including Klinefelter syndrome, 46,XX male syndrome, 47,XYY syndrome, Y chromosome microdeletions (AZF), and CFTR mutations. In female infertility, aneuploidies related to advanced maternal age, Turner syndrome, trisomy X, gonadal dysgeneses like Swyer syndrome, and X-chromosome structural rearrangements are influential. Additionally, conditions such as endometriosis, polycystic ovary syndrome (PCOS), and premature ovarian insufficiency (POI) possess distinct genetic and familial bases. High-resolution techniques like next-generation sequencing (NGS) facilitate the identification of these defects, offering critical prognostic value for reproductive and child health in assisted reproductive technologies (ART).
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