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The present study is aimed to explore the impact of experimental diabetes and insulin replacement on epididymal secretory products, sperm count, motility, and fertilizing ability in albino rats. Prepubertal and adult male Wistar strain rats were made diabetic with a single intraperitoneal injection of streptozotocin (STZ), at 120 and 65 mg/kg body weight for prepubertal and adult rats, respectively. After 3 days of STZ administration, insulin was given to a group of diabetic rats at a dose of 3 U/100 g body weight, subcutaneously and killed after 20 days of treatment. STZ-diabetes significantly reduced the epididymal tissue concentrations of testosterone, androgen-binding protein, sialic acid, glycerylphosphoryl choline, and carnitine, suggesting its adverse effects on the secretory activity and concentrating capacity of epididymal epithelium. Impaired cauda epididymidal sperm motility and fertility (in vivo) of STZ-diabetic rats imply the defective sperm maturation. Insulin replacement prevented these changes either partially or completely. From the above findings, it is evident that STZ-diabetes has an adverse effect on sperm maturation, which may be due to the decrease in the bioavailability of testosterone and epididymal secretory products.
The present study is aimed to explore the impact of experimental diabetes and insulin replacement on epididymal secretory products, sperm count, motility, and fertilizing ability in albino rats. Prepubertal and adult male Wistar strain rats were made diabetic with a single intraperitoneal injection of streptozotocin (STZ), at 120 and 65 mg/kg body weight for prepubertal and adult rats, respectively. After 3 days of STZ administration, insulin was given to a group of diabetic rats at a dose of 3 U/100 g body weight, subcutaneously and killed after 20 days of treatment. STZ-diabetes significantly reduced the epididymal tissue concentrations of testosterone, androgen-binding protein, sialic acid, glycerylphosphoryl choline, and carnitine, suggesting its adverse effects on the secretory activity and concentrating capacity of epididymal epithelium. Impaired cauda epididymidal sperm motility and fertility (in vivo) of STZ-diabetic rats imply the defective sperm maturation. Insulin replacement prevented these changes either partially or completely. From the above findings, it is evident that STZ-diabetes has an adverse effect on sperm maturation, which may be due to the decrease in the bioavailability of testosterone and epididymal secretory products.
Follicle stimulating hormone (FSH) interacts with its cognate receptor (R) on Sertoli cells within the testis and plays an important role in the maintenance of spermatogenesis. Male FSH-R knockout (FORKO) mice show fewer Sertoli cells and many that are structurally abnormal and as a consequence fewer germ cells. Lower levels of serum testosterone (T) and androgen binding protein (ABP) also occur, along with reduced fertility. To assess the effects of FSH-R depletion as an outcome of testicular abnormalities, sperm from the cauda epididymidis were counted and examined ultrastructurally. As reduced fertility may also reflect changes to the epididymis, the secondary responses of the epididymis to lower T and ABP levels were also examined by comparing differences in sizes of epididymal tubules in various regions of FORKO and wild type (WT) mice. Sperm motility was evaluated in FORKO mice and compared to that of WT mice by computer assisted sperm analysis (CASA). Quantitatively, the data revealed that epithelial areas of the caput and corpus epididymidis were significantly smaller in FORKO mice compared to WT mice. Cauda epididymal sperm counts in FORKO mice were also much lower than in WT mice. This resulted in changes to 9 out of 14 sperm motility parameters, related mostly to velocity measures, which were significantly lower in the FORKO mice. The greatest change was observed relative to the percent static sperm, which was elevated by 20% in FORKO mice compared to controls. EM analyses revealed major changes to the structure of the heads and tails of cauda luminal sperm in FORKO mice. Taken together these data suggest a key role for the FSH receptor in maintaining Sertoli cells to sustain normal sperm numbers and proper shapes of their heads and tails. In addition, the shrinkage in epididymal epithelial areas observed in FORKO mice likely reflect direct and/or indirect changes in the functions of these cells and their role in promoting sperm motility, which is noticeably altered in FORKO mice.
The mechanisms underlying the antifertility effects of hyperprolactinemia have yet to be established in an appropriate experimental model. Hyperprolactinemia is a known side effect of fluphenazine, a broad spectrum, long-acting phenothiazine known to be dopamine type-D2 receptor antagonist. In our earlier study in adult male rats, we reported that fluphenazine at a dose of 3 mg/kg/day suppressed serum FSH but not testosterone (T) through increasing dopamine (DA) metabolism in the pituitary gland, within 60 days. Fluphenazine treatment affected sperm quality and male rats treated with fluphenazine sired fewer litters. The effects of fluphenazine-induced hyperprolactinemia on sperm quality appeared to be related to reduced FSH. We now report that FSH suppression enhanced the uptake of acridine orange (AO), a DNA intercalating, fluorescent dye by the fluphenazine-treated caput epididymal sperms with concomitant reduction in the uptake of thiol-specific monobromobimane (mBBr) fluorescent dye in vitro, suggesting greater accessibility of DNA intercalating dye to sperm chromatin and reduction in free sperm protein thiols. The concomitant increase in AO and decrease in mBBr fluorescence was suggestive of loose chromatin packaging in caput epididymal sperms after treatment with fluphenazine at 3 mg/kg/day for 60 days. The suppression in levels of protamine (P1) in caput epididymal sperms suggested that chromatin hypocompaction was due to reduced deposition of protamines in sperm chromatin. Reduction in testicular levels of cyclic adenosyl 3', 5' monophosphate response element modulator (CREMtau) and P1 further suggested that reduced deposition was indeed due to reduced synthesis. The concomitant reduction in testicular levels of transition protein 1 (TP1) and transition protein 2 (TP2) also suggested that hypoprotamination was due to reduced synthesis of these proteins crucial for facilitating P1 deposition. The effect appeared to have occurred at the level of translation of CREMtau, since its transcript levels were unaffected whereas those of TP1, TP2 and P1 and protamine were upregulated. The study led to the view that the effects of FSH suppression were manifest on the posttranscriptional modifications of CREMtau, as also on transcript repression of TP1, TP2, P1, which do the RNA- binding proteins bring about. Reduction in FSH did not decrease ABP expression in the testis, which has recently been implicated in the expression of transition protein 1 in vitro. However, a significant reduction was evident after fluphenazine treatment, in the immunoexpression of testicular cAMP, the mediator of FSH effects in the Sertoli cells and putative mediator of ABP effects in the spermatids. The study suggests that fluphenazine-induced hyperprolactinemia suppressed FSH and affected a putative cAMP-dependent mechanism underlying posttranscriptional modification of spermatidal genes involved in chromatin condensation, presumably by reducing the availability/secretion of ABP, a paracrine regulator of spermiogenesis in vitro.
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