Androgen levels and apoptosis in the testis during postnatal development of finasteride-treated male rat offspring

Abstract

Introduction. The hormone-dependent events that occur throughout the first wave of spermatogenesis, such as the establishment of the number of Sertoli cells (SCs) and spermatogonial stem cells (SSCs) within the seminiferous cords and the setting up of the blood-testis barrier, are important for adult male fertility. Any changes in the T/DHT ratio can result in male subfertility or even infertility. In this study we aimed to evaluate effects of paternal exposure to 5-alpha reductase type 2 inhibitor, finasteride on litter size, androgen levels and germ cell apoptosis in male offspring during postnatal development. Material and methods. The subjects of the study were 7, 14, 21/22, 28, and 90-day-old Wistar male rats (F1:Fin) born from females fertilized by finasteride-treated rats. Offspring born from untreated parental animals were used as a control group (F1:Control). Animals and the collected testes were weighed, blood and intratesticular levels of T and DHT were measured by ELISA, and the apoptotic index of testicular cells was evaluated by TUNEL technique. Results. We observed difficulties in obtaining male newborns from female rats fertilized by finasteride-treated male rats. In the F1:Fin rats, changes in the body and testes weights occurred, and a lower number of apoptotic cells was found during postnatal maturation of the seminiferous epithelium. Changes in androgen concentrations during the first spermatogenesis wave and adult life were also evident. Conclusion. Finasteride treatment of male adult rats may not only cause a decrease in the fertility of parental rats, but also could lead to incorrect, androgen-sensitive course of spermatogenesis in their offspring.

Knockdown of Sucla2 decreases the viability of mouse spermatocytes by inducing apoptosis through injury of the mitochondrial function of cells

“…Mitochondria are multitasking organelles [28], and many environmental and stress stimuli can cause mitochondrial dysfunction [29,30], thereby affecting spermatogenesis [31][32][33][34]. The present study is a follow-up to our previous works, which showed that Sucla2 expression decreased in testes and GC1 cells with increasing apoptotic cells after exposure to endocrine disruptor BDE47 [8].…”

Impaired expression of testicular androgen receptor and collagen fibers in the testis of diabetic rats under HAART: the role of Hypoxis hemerocallidea

“…Male mice lacking SCARs were reported to be associated with infertility, as spermatogenesis rarely progress beyond meiosis [55,56]. Several spermatogenic disorders are associated with impaired androgenic stimulation of Sertoli cells; thus, low levels of the AR are likely to be involved in spermatogenic disorders [57] or incorrect androgen-sensitive course of spermatogenesis [58].…”

Antioxidant enzyme expression of mRNA and protein in the epididymis of finasteride-treated male rat offspring during postnatal development

“…The objective of the experiment was to sample the epididymis from both the treated and untreated offspring (F1) at 7, 14, 21, 28, and 90 postnatal days (PND) of life. Detailed information on the design of the animal treatment, mating, and collection of newborn offspring has been presented in our previous report [38]. After thiopental anesthesia (120 mg/kg bw, i.p., Biochemie GmbH, Vienna, Austria), the epididymides were weighed and the right epididymides (5 animals per age group in the F1 generation) used for immunohistochemical (IHC) reactions, and the left epididymides frozen and used for qRT-PCR analysis.…”

“…During the first 2 weeks of life (Figures 8 F, G) GR was expressed across the cell cytoplasm (white asterisk), in particular at the cell apex (red arrows). At PND 21 immunostaining in the F1:Fin group became low (Figure 8 H) Table III shows the blood serum level of androgens presented in our previous study [38], which was used to make correlations with the levels of antioxidant enzyme mRNA.…”

“…In our previous study we showed that treatment with finasteride (an inhibitor of 5α-reductase type 2) in adult male rats influenced the patterns of E-SOD, GPX5, and Cu/ZnSOD expression; that change was region-dependent and the expression was up-or down-regulated compared to control animals [37]. Recently, we also found that finasteride treatment of paternal rats resulted in altered serum and intratesticular levels of testosterone (T) and dihydrotestosterone (DHT) in their male offspring [38,39]. Consequently, it can be speculated that finasteride, a drug that modulates the activity of the key enzyme involved in the metabolism of T, can act in a similar fashion to endocrine disruptors (EDs), and can negatively influence epididymal protection of spermatozoa against oxidative stress.…”