Ovaryum Follikül Gelişimi Üzerine Etkili TGF-Β Ailesi Büyüme Faktörleri
Synopsis
Bu derleme, transforme edici büyüme faktörü beta (TGF-β) ailesinin memeli ovaryumlarında follikül gelişimi (follikülogenezis) üzerindeki hücresel ve fizyolojik rollerini incelemektedir. TGF-β ailesi üyeleri; TGF-β, kemik morfogenetik proteini (BMP), büyüme farklılaşma faktörü (GDF) ve aktivin/inhibin gibi alt ailelerden oluşmakta olup otokrin ve parakrin mekanizmalarla etki gösterirler. Primordial folliküllerin aktivasyonu ve gelişiminde BMP-4 ve BMP-7 pozitif bir rol oynarken, antimüllerian hormon (AMH) primordial follikül gelişimini ve FSH duyarlılığını baskılayarak negatif bir düzenleyici olarak görev yapar. Oosit kaynaklı GDF-9 ve BMP-15 (GDF-9b), erken follikül evrelerinde granüloza hücre proliferasyonunu uyarır; bu faktörlerin eksikliği veya mutasyonları türlere bağlı olarak infertiliteye yol açabilmektedir. Erken ve antral evrelerde aktivinler granüloza hücre proliferasyonu ile FSH reseptör ekspresyonunu artırırken, inhibin A tekal androjen üretimini destekler ve oosit matürasyonunu olumsuz etkileyebilir. Follikül gelişiminin yanı sıra ovülasyon, luteinizasyon ve korpus luteum oluşumunda da TGF-β izoformları apoptozisi inhibe ederek ve progesteron sentezini destekleyerek kritik işlevler üstlenir. Sonuç olarak, bu büyüme faktörleri insan ve evcil memelilerde üreme verimliliğini artırmaya yönelik potansiyel önem taşımaktadır.
This review examines the cellular and physiological roles of the transforming growth factor-beta (TGF-β) family in mammalian ovarian follicle development (folliculogenesis). Members of the TGF-β family, which include subfamilies such as TGF-β, bone morphogenetic proteins (BMPs), growth differentiation factors (GDFs), and activins/inhibins, exert their effects via autocrine and paracrine mechanisms. While BMP-4 and BMP-7 play positive roles in the activation and development of primordial follicles, anti-Müllerian hormone (AMH) acts as a negative regulator by suppressing primordial follicle growth and FSH sensitivity. Oocyte-derived GDF-9 and BMP-15 (GDF-9b) stimulate granulosa cell proliferation during early follicular stages, and mutations or deficiencies in these factors can lead to species-dependent infertility. In early and antral stages, activins enhance granulosa cell proliferation and FSH receptor expression, whereas inhibin A supports thecal androgen production and can negatively impact oocyte maturation. Beyond follicular development, TGF-β isoforms play critical roles in ovulation, luteinization, and corpus luteum formation by inhibiting apoptosis and promoting progesterone synthesis. Consequently, these growth factors hold significant potential for enhancing reproductive performance in humans and domestic mammals.
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