title: Post-fertilization effect of bilateral primary testicular damage induced by unilateral cryptorchidism in the rat model.
abstract: Cryptorchidism, a common anomaly of the male genitalia, affects 2-4% of male infants. The post-fertilization effects of unilateral cryptorchidism model in the rat and the effects of antioxidant treatment were investigated. Six-week-old male Wistar rats were randomly separated into four groups. Unilateral cryptorchidism was induced in the right testis of three groups. One group was treated with saline intraperitoneally (i.p.) (Crypto), one group was treated with taurine (500 mg/kg, i.p.; Tau), and another group was treated with sivelestat (15 mg/kg i.p.; Siv). The control group was treated with saline i.p. The treatment was daily for 8 weeks. Five days before sacrifice, mating studies were performed. Body, testicular, and epididymal weights were recorded. Malondialdehyde (MDA) levels in the seminal vesicular fluid (SVF) were measured. Testicular levels of MDA and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined bilaterally. TUNEL assay was used to examine DNA fragmentation bilaterally. Histological examination and the Johnsen score were used to evaluate morphological testicular alterations. The Crypto group demonstrated significantly lower right testicular and epididymal weights, significantly increased SVF-MDA levels, testicular MDA and 8-OHdG levels, and the apoptotic score bilaterally compared to the controls. Furthermore, histological evaluation revealed significantly reduced spermatogenesis and mild injury to the cryptorchid testes compared to the control. Treatment with both taurine and sivelestat significantly reduced SVF-MDA levels, testicular MDA, 8-OHdG, and apoptosis bilaterally compared to the Crypto group. Antioxidant treatment was unable to ameliorate spermatogenesis. Newborns delivered by females that mated with Crypto-males had significantly lower body weight compared with the respective animals from the control, Tau and Siv groups. The present study demonstrated that unilateral cryptorchidism-induced testicular damage can significantly affect the contralateral testis as well having further deleterious post-fertilization effect on the development of newborns. Treatment with antioxidants can partially improve the testicular damage bilaterally with beneficial effects for the newborns.
authors.affiliation: Division of Urology, Department of Surgery, Tottori University School of Medicine, Yonago, Japan.
authors.forename: P
authors.identifier: http://orcid.org/0000-0002-6202-8653
authors.initials: P
authors.lastname: Tsounapi
authors.affiliation: Division of Urology, Department of Surgery, Tottori University School of Medicine, Yonago, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.affiliation: Department of Urology, School of Medicine, University of Ioannina, Ioannina, Greece.
authors.forename: F
authors.initials: F
authors.lastname: Dimitriadis
authors.affiliation: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Division of Urology, Department of Surgery, Tottori University School of Medicine, Yonago, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hikita
authors.affiliation: Division of Urology, Department of Surgery, Tottori University School of Medicine, Yonago, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Muraoka
authors.affiliation: Division of Urology, Department of Surgery, Tottori University School of Medicine, Yonago, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sejima
authors.affiliation: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.affiliation: Division of Molecular Pharmacology, Department of Pathophysiological and Therapeutic Science, Tottori University School of Medicine, Yonago, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tomita
authors.affiliation: Department of Urology, School of Medicine, University of Ioannina, Ioannina, Greece.
authors.forename: N
authors.initials: N
authors.lastname: Sofikitis
authors.affiliation: Division of Urology, Department of Surgery, Tottori University School of Medicine, Yonago, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Takenaka
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000627:therapeutic use*; D003456:Cryptorchidism / Q000188:drug therapy / Q000473:pathology*; D047108:Embryonic Development; D005260:Female; D005298:Fertility; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000627:therapeutic use*; D013654:Taurine / Q000627:therapeutic use*; D013737:Testis / Q000187:drug effects / Q000473:pathology*
chemical_list: D000975:Antioxidants; D013449:Sulfonamides; D013654:Taurine; C069195:sivelestat; D005998:Glycine
keywords: DNA oxidative damage; antioxidant treatment; cryptorchidism; germ cell apoptosis; oxidative stress; postnatal development; seminal vesicular fluid; testis