İNTRASEREBROVENTRİKÜLER SPEXIN İNFÜZYONUNUN HİPOTALAMUS-HİPOFİZ-TESTİS AKSI ÜZERİNE ETKİLERİ
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2023-08
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info:eu-repo/semantics/openAccess
Özet
İnfertilite, dünya genelinde yaklaşık 70 milyon insanı etkileyen önemli bir durumdur. Erkek infertilitesinin bozulmuş spermatogenez, düşük sperm sayısı, anormal sperm morfolojisi, beslenme ve endokrin bozukluklar, alkol ve sigara kullanımı gibi birçok sebebi bulunmaktadır. İnfertiliteyi etkileyen tüm bu sebeplerin erkek üreme fizyolojisinde önemli bir role sahip olan hipotalamus–hipofiz–testiküler (HHT) aksın yapısını da bozduğu ve bunun sonucunda da gonadların fizyolojik seviyede testosteron ve sperm üretememesine neden olduğu bilinmektedir. Spexin (SPX); kemirgenlerin ve insanların merkezi sinir sisteminde, karaciğerinde, gonadlarında ve böbrek gibi birçok periferik dokularında yaygın olarak eksprese edilen bir peptid hormondur. SPX’in insülin salınımında, yağ metabolizmasında, beslenme davranışında ve üreme fonksiyonlarının düzenlenmesinde etkin bir nöromodülatör olarak rol oynadığı yapılan birçok çalışmada gösterilmiştir. Son yıllarda ise esas olarak SPX’in üremenin düzenlemesindeki rolüne odaklanılmıştır. Bu çalışmada SPX’in intraserebroventriküler (icv) infüzyonunun hypothalamus’ta GnRH mRNA seviyesi, serum LH, FSH ve testosteron seviyesi ve testis dokularında da histopatolojik değişiklikler üzerine olan etkileri incelenmiştir. Bu amaçla 40 adet Wistar albino sıçan kontrol, sham, Spexin 30 nmol ve Spexin 100 nmol olmak üzere dört gruba ayrıldı. Spexin 30 nmol grubundaki sıçanlara 7 gün boyuncu icv olarak 30 nmol/1 µl/saat SPX verilirken spexin 100 nmol grubundaki sıçanlara ise 100 nmol/1 µl/saat SPX verildi. Sham grubundaki sıçanlara ise 7 gün boyunca spexin çözücüsü olarak yBOS verildi. 7. günün sonunda sıçanlar dekapite edilerek kan ve doku örnekleri alındı. Elde edilen kan örnekleri serumlara ayrıldı ve LH, FSH ve testosterone hormon seviyeleri ELISA yöntemiyle belirlendi. Hypothalamus dokusunda GnRH mRNA ifade seviyesi RT-PCR yöntemiyle belirlenirken testis dokularında ise hematoksilen-eozin boyama yöntemiyle seminifer tübül çapı ve epital kalınlığı değerlendirildi. SPX uygulamasının hypothalamus dokusunda GnRH mRNA ifade seviyesini dozdan bağımsız olarak arttırdığı görüldü (p<0.05). Bunun yanı sıra yine SPX uygulanan gruplarda dozdan bağımsız olarak serum LH, FSH ve testosteron hormon seviyelerininin kontrol ve sham gruplarına göre istatistiksel olarak artış gösterdiği belirlendi (p<0.05). Histolojik değerlendirmeler sonucunda SPX uygulamasının seminifer epitel kalınlığı üzerinde gruplar arasında herhangi bir değişikliğe neden olmadığı görülürken tübül çapının SPX uygulanan gruplarda artış gösterdiği görüldü (p<0.05). Çalışmamız sonucunda elde edilen veriler, SPX’in hipotalamus-hipofiz-testis aksı aracılığıyla üreme fonksiyonlarının düzenlenmesinde önemli roller oynayabileceğini düşündürmektedir.
Infertility is an important condition affecting approximately 70 million people worldwide. Male infertility has many causes such as impaired spermatogenesis, low sperm count, abnormal sperm morphology, nutrition and endocrine disorders, alcohol and smoking. It is known that all these factors affecting infertility also disrupt the structure of the hypothalamus-pituitary-testicular (HHT) axis, which has an important role in male reproductive physiology, and as a result, the gonads cannot produce testosterone and sperm at physiological level. Spexin (SPX); It is a peptide hormone widely expressed in the central nervous system, liver, gonads and many peripheral tissues of rodents and humans. It has been shown in many studies that Spexin plays a role as an effective neuromodulator in insulin secretion, fat metabolism, nutritional behavior and regulation of reproductive functions. In recent years, the focus has been mainly on the role of spexin in the regulation of reproduction. In this study, the effects of intracerebroventricular (icv) infusion of spexin on GnRH mRNA level in hypothalamus, serum LH, FSH and testosterone levels and histopathological changes in testis tissues were investigated. For this purpose, 40 Wistar albino rats were divided into four groups as control, sham, Spexin 30 nmol and Spexin 100 nmol. The rats in the spexin 30 nmol group were given 30 nmol/1 µl/hour SPX icv for 7 days, while the rats in the spexin 100 nmol group were given 100 nmol/1 µl/hour SPX. The rats in the sham group were given yBOS as spexin solvent for 7 days. At the end of the 7th day, the rats were decapitated, and blood and tissue samples were taken. Obtained blood samples were separated into sera and LH, FSH and testosterone hormone levels were determined by ELISA method. While the level of GnRH mRNA expression in hypothalamus tissue was determined by RT-PCR method, seminiferous tubule diameter and epithelial thickness were evaluated in testicular tissues by hematoxylin-eosin staining method. It was observed that SPX application increased the level of GnRH mRNA expression in the hypothalamus tissue independently of the dose (p<0.05). In addition, serum LH, FSH and testosterone hormone levels were statistically increased in the SPX applied groups compared to the control and sham groups, regardless of the dose (p<0.05). As a result of histological evaluations, it was observed that SPX application did not cause any change in seminiferous epithelial thickness between groups, while tubule diameter increased in SPX applied groups (p<0.05). The data obtained as a result of our study suggest that SPX may play important roles in the regulation of reproductive functions through the hypothalamus-pituitary-testis axis."
Infertility is an important condition affecting approximately 70 million people worldwide. Male infertility has many causes such as impaired spermatogenesis, low sperm count, abnormal sperm morphology, nutrition and endocrine disorders, alcohol and smoking. It is known that all these factors affecting infertility also disrupt the structure of the hypothalamus-pituitary-testicular (HHT) axis, which has an important role in male reproductive physiology, and as a result, the gonads cannot produce testosterone and sperm at physiological level. Spexin (SPX); It is a peptide hormone widely expressed in the central nervous system, liver, gonads and many peripheral tissues of rodents and humans. It has been shown in many studies that Spexin plays a role as an effective neuromodulator in insulin secretion, fat metabolism, nutritional behavior and regulation of reproductive functions. In recent years, the focus has been mainly on the role of spexin in the regulation of reproduction. In this study, the effects of intracerebroventricular (icv) infusion of spexin on GnRH mRNA level in hypothalamus, serum LH, FSH and testosterone levels and histopathological changes in testis tissues were investigated. For this purpose, 40 Wistar albino rats were divided into four groups as control, sham, Spexin 30 nmol and Spexin 100 nmol. The rats in the spexin 30 nmol group were given 30 nmol/1 µl/hour SPX icv for 7 days, while the rats in the spexin 100 nmol group were given 100 nmol/1 µl/hour SPX. The rats in the sham group were given yBOS as spexin solvent for 7 days. At the end of the 7th day, the rats were decapitated, and blood and tissue samples were taken. Obtained blood samples were separated into sera and LH, FSH and testosterone hormone levels were determined by ELISA method. While the level of GnRH mRNA expression in hypothalamus tissue was determined by RT-PCR method, seminiferous tubule diameter and epithelial thickness were evaluated in testicular tissues by hematoxylin-eosin staining method. It was observed that SPX application increased the level of GnRH mRNA expression in the hypothalamus tissue independently of the dose (p<0.05). In addition, serum LH, FSH and testosterone hormone levels were statistically increased in the SPX applied groups compared to the control and sham groups, regardless of the dose (p<0.05). As a result of histological evaluations, it was observed that SPX application did not cause any change in seminiferous epithelial thickness between groups, while tubule diameter increased in SPX applied groups (p<0.05). The data obtained as a result of our study suggest that SPX may play important roles in the regulation of reproductive functions through the hypothalamus-pituitary-testis axis."
Açıklama
Anahtar Kelimeler
İntraserebroventriküler, Spexin, FSH, LH, GnRH, histopatoloji, Intracerebroventricular, Spexin, FSH, LH, GnRH, histopathology