Gizem KABASAKAL, Emine TURAL, Murat Serkant ÜNAL

DENEYSEL OVERYAN YETMEZLİKLERDE MEZENKİMAL KÖK HÜCRELERİN OVARYUM DOKUSUNA ETKİSİ

Prematür Overyan Yetmezlik (POY), folikül stimülan hormonun (FSH) yüksek düzeylerinin (40 IU/I ve üzeri) eşliğinde, 40 yaşından küçük bir hastada menstrüel siklusların düzeninin 4-6 aydan uzun bir süre boyunca kesilmesi olarak tanımlanmaktadır. Etyolojisinde genetik nedenler, toksik ajanlar, cerrahi girişimler, otoimmün nedenler, enfeksiyonlar ve kalıtsal problemler bulunabilir. Reprodüktif dönemde kadın hastaların kanser tedavisi için kullandıkları kemoterapik ajanlar, sitotoksik etkilidir. Kemoterapik ajanlar hem oosit hem de oositi çevreleyen granüloza hücrelerinde hasara neden olarak folikül kaybı ve buna bağlı olarak da prematür over yetmezliğine sebep olmaktadır. Primordial folikül aktivasyonunda oluşabilecek bir düzensizlik over rezerv kaybına ve prematür menopoza yol açabilmektedir. Primordial folikülden primer foliküle geçişte, kontrollü aktive edici ve baskılayıcı rol oynayarak folikül havuzunun korunmasında rol alan sinyal yolakları birbirinden bağımsız ancak dengeli bir şekilde çalışır. Dengenin bozulduğu durumlarda, folliküllerin kitlesel aktivasyonu ve folikül havuzunun erkenden tükenmesi meydana gelmektedir. Overyan rezervin değerlendirilmesinde serum FSH, anti-Müllerian hormon (AMH), inhibin B ölçümleri ve ultrasonografi ile over hacmi ölçümü, antral folikül sayımı (AFS) ölçümü yapılır. POY, anovulasyonun yaygın nedenlerinden biridir. Kadınlarda kemoterapiye bağlı POY’nin azaltması, over dokusunun yenilenmesi ve hem endokrin hem de ekzokrin fonksiyonlarını geri kazanılması için birçok tedavi yöntemi araştırılmaktadır. Son zamanlarda birçok çalışmaya konu olan mezenkimal kök hücreler (MKH) stromal kökenli multipotent özellikte erişkin kök hücreleridir. Göbek kordonu, adipoz doku, plasenta, kemik iliği, ovaryum dokusu, amniyotik sıvı, endometriyal doku, karaciğer gibi birçok dokudan izole edilebilirler. MKH’lerin antiapoptotik, anjiojenik, antifibrotik özellikleri bulunmaktadır. Uyguladıkları dokularda immün yanıta neden olma ihtimalleri de düşüktür. Bu özellikleri sayesinde doku hasarı onarımında ve yenilenmesinde önemli roller üstlenirler. Yapılan deneysel çalışmalarda çeşitli kaynaklardan elde edilen MKH’lerin, overyan yetmezlikte foliküler gelişime katkısı ve overyan fonksiyonlara olumlu etkileri araştırılmıştır. Elde edilen sonuçlar, şu an için çözümsüz olan bazı POY olgularının tedavisinde MKH'ler ile ilgili gelecekteki klinik çalışmalara ışık tutabilir. Bu derlemedeki amacımız farklı kaynaklardan izole edilen MKH’lerin POY hastalarının over dokusu üzerindeki özelliklerini araştırmaktır.

Anahtar Kelimeler:

Mezenkimal kök hücre, Folikül, Ovaryum, Kemoterapi

EFFECT OF MESENCHYMAL STEM CELLS ON OVARIUM TISSUE IN EXPEREMENTAL OVARIAN FAILURE CASES

Premature ovarian failure (POF) is defined as the cessation of regular menstrual cycles for more than 4-6 months in woman under 40 years of age, accompanied by high follicle stimulating hormone (FSH) levels (40 IU/I and above). There can be found various etiologies of POF such as; genetic causes, toxic agents, surgical interventions, autoimmune causes, infections and hereditary problems. Chemotherapy agents used by female patients in the reproductive period for cancer treatment are cytotoxic. Chemotherapy agents cause damage to both the oocyte and the granulosa cells surrounding the oocyte, resulting in follicle loss and consequently premature ovarian failure. An irregularity in primordial follicle activation may lead to loss of ovarian reserve and premature menopause. In the transition from the primordial follicle to the primary follicle, the signaling pathways that play a controlled activating and suppressor role in protecting the follicle pool work independently but in a balanced way. In cases where the balance is disturbed, mass activation of the follicles and prematüre depletion of the follicle pool occurs. In the evaluation of ovarian reserve, serum FSH, anti-Müllerian hormone (AMH), inhibin B measurements and ovarian volume measurement by ultrasonography, antral follicle count (AFS) are performed. POF is one of the common causes of anovulation. Many treatment methods are being investigated to reduce the chemotherapy-induced POF in women, to regenerate ovarian tissue and to restore both endocrine and exocrine functions. Mesenchymal stem cells (MSCs), which have been the subject of many studies recently, are adult stem cells of stromal origin with multi-potential properties. MSCs can be isolated from many tissues such as umbilical cord, adipose tissue, placenta, bone marrow, ovarian tissue, amniotic fluid, endometrial tissue, liver. MSCs have properties like that of antiapoptotic, angiogenic, antifibrotic. They are also uncommon to create an immune response in the tissues they are administered. Through these properties, they act an important role in tissue damage repair and renewal. In experimental studies, it has been shown that MSCs obtained from various sources improve ovarian failure follicular development and ovarian functions. The results obtained may shed light on future clinical studies of MSCs in the treatment of some POF cases that are currently unsolved. Our aim in this review is to investigate the properties of MSCs isolated from different sources on ovarian tissue in POF patients.

Keywords:

Mesencymal stem cell, Follicle, Ovary, Chemotherapy,

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