nfertilite Testleri 1 Semende veya TESEde haploidi paneli

İnfertilite Testleri 1. Semende veya TESE’de haploidi paneli § Sperm FISH § Spermatogenez Marker Tayini 2. Sperm DNA Hasar Paneli § Semende Oksidatif Stres Tayini ( ROS) § Semende Apoptozis Tayini § Sperm DNA Hasar 3. Erkek/ Kadın Infertilite Paneli >25 gende mutasyon taraması ( örn : CFTR, FSHR, AR, DMC 0, TEX 101)

Testislerde Sperm Var mı? TESE Öncesi Yol Gösterebilecek Markerlar : PCNA, Lim 15, ESX 1 ve TEX 101 Referans : • PCNA FSH tedavisinde marker olarak kullanılan mitoz ile ilişkili bir proteindir. • Lim 15 geni ekspresyon analizi testis dokusu içinde sperm yapımını sağlayan mayoz bölünmenin olup olmadığını veya olma potansiyelini (olabileceğini) gösteren önemli bir belirteçtir. • ESX 1 testis gelişiminde görev alır ve sperm kök hücrelerinden sırasıyla spermatosit (preleptoten), spermatidler ve olgun sperm hücrelerinin (spermatozoa) gelişmesini indükler. • Sperm üretiminin olduğu ve sperm tahlilinde normal düzeyde sperm çıkan olgularda TEX 101 miktarı anlamlı derecede yüksek bulunur. Oysa sperm üretiminin hiç olmadığı Sertli Cell Only (SCO) sendromu olgularında bunun miktarı sıfıra yaklaşır. • Bu dört genin Real Time PCR ile semen veya dokuda ekspresyon seyiyelerine bakmak ve sperm pozitif örnekler ile karşılaştırmak hasta tedavisinde bilgi verici olacaktır. Foresta C, Selice R, Ferlin A, Garolla A. Recombinant FSH in the treatment of oligozoospermia. Expert Opin Biol Ther. 2009 May; 9(5): 659 -66. Hamada FN et al. (2007): Proliferating cell nuclear antigen (PCNA) interacts with a meiosis-specific Rec. A homologues, Lim 15/Dmc 1, but does not stimulate its strand transfer activity. Biochemical and Biophysical Research Communications 352: 836– 842 Shinjo E, Shiraishi K, Matsuyama H. The effect of human chorionic gonadotropin-based hormonal therapy on intratesticular testosterone levels and spermatogonial DNA synthesis in men with non-obstructive azoospermia. Andrology. 2013 Nov; 1(6): 929 -35 Shiraishi K, Ohmi C, Shimabukuro T, Matsuyama H. Human chorionic gonadotrophin treatment prior to microdissection testicular sperm extraction in non-obstructive azoospermia. Hum Reprod. 2012 Feb; 27(2): 331 -9.

Semende Apoptozis Tayini v Testin amacı infertil/subfertil erkek hasta grubunda özellikle erken apoptotik ve geç apoptotik (nekrotik) sperm oranlarını tespit ederek infertilite tedavisinin ve takibinin yapılmasına kılavuzluk etmektir.

Semende Oksidatif Stres Tayini ROS SONUÇU 0, 235 Mv/(milyonsperm/ml). Düşük oksidatif stres tespit edilmiştir. Cut-off değeri <1, 42 Mv/(milyonsperm/ml) v Oksidatif stres nükleotid degredasyonu ile DNA fragmentasyonuna yol açmaktadır ve proteinlerin üç boyutlu yapısının bozulmasına neden olmaktadır. Bu durum erkeklerde fertilitenin düşmesine neden olmaktadır.

ERKEK İNFERTİLİTE PANELİ Spermatogenesis Failure / Arrest GENLERİ TFF ( ion channels) GENLERİ HORMONES/ RECEPTORS GENLERİ Meiotic Expression FUNCTION Geneticmaleinfertilityandmutation of CATSPER ionchannels. PLCZ 1 may control cell cycle-dependent Ca(2+) oscillations in early embryogenesis FUNCTION Inactivatingmutations of thehumanluteinizinghormonereceptor in bothsexes. The FSH receptor (FSHR) gene is also being studied for involvement in spermatogenesis. deliveringsexhormonestotargettissuesandcontrollingtheconcentration of androgens Hypogonadotropic hypogonadism Longerlengths of the CAG polymorphismareassociatedwithdecreasedtranscriptionalactivity of the AR gene in infertile men, suggestingthatlongerpolyglutaminetractsarerelatedtomalefactorinfertility GRTH/DDX 25), a negative regulator of luteinizing/chorionic gonadotropin hormone-induced steroidogenesis in Leydig cells Studies have found an association between abnormal spermatogenesis ande strogenin sufficiency, prompting th einvestigation of the ESR genes Studies have found an association between abnormal spermatogenesi san destrogenin sufficiency, prompting the investigation of the ESR genes ABSENCE OF VAS DEFERANS GENLERİ congenital bilateral absence of the vas deferens( CRYPTORCHıDıSM GENLERİ HYPOGONADISM GENLERİ CILIARY DYSKINESIA GENLERİ SPERM PROTAMINE GENLERİ FUNCTION Cryptorchidism FUNCTION protamines, the major DNA-binding proteins in the nucleus of sperm in most vertebrates,

KADIN İNFERTİLİTE PANELİ Ovarian Dysgenesis Genleri Receptor follicle stimulating hormone and functions in gonad development Involved in oocyte maturation and follicular development Co-activates ligand-driven transcription mediated by estrogen, androgen, glucocorticoid, progesterone, and thyroid nuclear receptors Required for eukaryotic DNA replication initiation and the early stage of elongation LH Resistance Genleri Receptor for both luteinizing hormone and choriogonadotropin Premature Ovarian Failure Genleri Involved in m. RNA trafficking from the nucleus to the cytoplasm Plays a role in the development and normal function of the ovaries May play a role in the etiology of premature ovarian failure Essential for ovary differentiation and maintenance, and repression of the genetic program for somatic testis determination Essential for folliculogenesis and regulation of oocyte-specific genes Plays a key regulatory role in the expression of multiple oocyte-specific genes, including those that initiate folliculogenesis and those that encode the zona pellucida (ZP 1, ZP 2 and ZP 3) required for fertilization and early embryonic survival Binds the core motif AGGTCA and regulates many genes involved in reproduction, steroidogenesis, and sexual differentiation Essential for proper pairing and segregation of chromosomes during meiosis Functions in genome integrity in germline tissue Involved in homologous recombination repair following DNA interstrand cross-links and plays a key role during gametogenesis

KADIN İNFERTİLİTE PANELİ Hypogonadotropic Hypogonadism Genleri Promotes spermatogenesis and ovulation by stimulating the testes and ovaries to synthesize steroids Low Functional Ovarian Reserve Genleri Catalyzes the 3 -prime-phosphoadenosine 5 -prime-phosulfate-dependent sulfation of a wide variety of steroids in human liver and adrenal tissue and is responsible for sulfation of bile acids in human liver Catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone (DHT) Converts testosterone (T) into 5 -alpha-dihydrotestosterone (DHT) and progesterone or corticosterone into their corresponding 5 -alpha-3 -oxosteroids. It plays a central role in sexual differentiation androgen physiology Oocyte Meiosis I Arrest Genleri Expressed exclusively in the oocyte and early embryo, where it accounts for almost all of the expressed beta-tubulin Ovarian dysfunction, hypergonadotrophic hypogonadism and acromesomelic chondrodysplasia Autosomal 46, XY, male-to-female sex reversal (phenotypically perfect females) CHARGE syndrome and Kallmann syndrome (KAL 5) Normosmic hypogonadotrophic hypogonadism and Kallmann syndrome (KAL 6) Kallmann syndrome (KAL 2) Premature ovarian failure (POF 1) associated with premutations Normosmic hypogonadotrophic hypogonadism Hypogonadotrophic hypogonadism and insomnia, X-linked Kallmann syndrome (KAL 1) Hypogonadotrophic hypogonadism Hypergonadotrophic hypogonadism (luteinizing hormone resistance) X-linked congenital adrenal hypoplasia with hypogonadotrophic hypogonadism; dosage-sensitive male-to-female sex reversal Normosmic hypogonadotrophic hypogonadism and Kallmann syndrome (KAL 4) Kallmann syndrome (KAL 3) 46, XX, female-to-male sex reversal (individuals contain testes) Mutations lead to 46, XY females; translocations lead to 46, XX males Autosomal 46, XY male-to-female sex reversal (campomelic dysplasia) Normosmic hypogonadotrophic hypogonadism Dysfunctional zona pellucida formation