Preventive effect of Pueraria mirifica on testosterone‐induced prostatic hyperplasia in Sprague Dawley rats

Pueraria mirifica (PM) extract contains phytoestrogen daidzein and genistein. In this study, we investigated the protective effect of PM extract, daidzein and genistein on a testosterone‐induced prostatic hyperplasia in rats. Testosterone was administered at 3 mg kg^?1 to rats followed by the PM extract, daidzein and genistein for a period of 30 days with finasteride as positive control. The testosterone level was increased, indicating inhibition of 5α‐reductase converting testosterone to dihydrotestosterone. This was confirmed by prostate‐specific antigen level that significantly decreased when treated with PM extract, daidzein and genistein. The PM extract, daidzein and genistein reduced the increase in the prostate/body weight ratio in testosterone‐induced rats. This gives indication that PM extract, daidzein and genistein possessed protective activity for the treatment of benign prostatic hyperplasia. The analysis of histoarchitechture of the prostate has also shown that there was a significant improvement in prostatic cells of the testosterone‐induced rats when treated with PM extract, daidzein and genistein.     

Effects of date seed oil on testicular antioxidant enzymes and epididymal sperm characteristics in male mice

The aim of this study was to evaluate the effect of date seed oil (DSO) on epididymal sperm characteristics and testicular antioxidant enzymes in male mice. DSO was diluted into isotonic saline solution (0.9%) and different doses (5, 10, 15 and 20%) were prepared. Fifty male mice were divided into five groups; in four groups DSO was given by intraperitoneal injection of oil solution for 28 days. The control group was injected by isotonic saline solution without DSO. Body and reproductive organ weights, sperm characteristics (count, motility, viability and morphology) were assessed. In addition, levels of malondialdehyde (MDA), activities of superoxide dismutase (SOD) and catalase (CAT) were investigated in testes. A significant increase in sperm count, motility and viability of all treated animal groups was observed when compared with the control group ( P  < 0.05). Unlike, the percentage of abnormal sperm was significantly lower in all treated groups than in the control group ( P  < 0.05). A significant decrease in MDA levels and marked increase in SOD and CAT activities in mice treated with high doses of DSO (15 and 20%) were also noted. We suggest that DSO can improve the epididymal sperm quality and could ameliorate the testicular strategy defences.     

Effect of kolaviron,a biflavonoid complex from Garcinia kola seeds,on the antioxidant,hormonal and spermatogenic indices of diabetic male rats

The antihyperglycaemic effect of kolaviron (KV), a biflavonoid from Garcinia kola has been established in previous studies. In this study, we investigated the effect of KV (200 mg kg^?1) on the antioxidant, hormonal and spermatogenic indices of alloxan‐diabetic male rats, and metformin hydrochloride (MET) (30 mg kg^?1) served as standard drug. The results showed that KV and MET significantly (P < 0.05) decreased the fasting blood glucose of the diabetic rats. Also, untreated and MET‐treated diabetic groups had significantly (P < 0.05) lower body‐weight gain and relative weights of testes. In addition, epididymal sperm abnormalities were increased, whereas sperm count, motility, testicular protein and sialic acid were decreased in untreated diabetic group. Also, antioxidant parameters, reduced glutathione, catalase, superoxide dismutase, glutathione‐S‐transferase and glutathione peroxidase were significantly (P < 0.05) reduced in the testes with a concomitant increase in lipid peroxidation in untreated diabetic group. Furthermore, untreated diabetic group had significantly (P < 0.05) lower levels of testosterone, luteinising and follicle‐stimulating hormones relative to controls. Treatment with KV restored the relative weights of testes, activities of antioxidant enzymes, sperm and hormonal indices of the diabetic animals. This study demonstrated the role of KV to promote fertility in diabetic male rats by enhancing the hormonal and antioxidant status of the rats.     

Rose oil inhalation protects against formaldehyde-induced testicular damage in rats

In this experimental study, harmful effects of formaldehyde (FA) inhalation on sperm concentration, sperm quality, serum testosterone levels and the rat testes were investigated. In addition, the possible protective effects of rose oil against to these harmful effects were evaluated. For this purpose, 21 albino-Wistar rats were used. The rats in Group I were used as control group. When the rats of Group II were exposed FA (10 ppm/1 h) for 35 days, the rats of Group III inhalated rose oil (1 ml/1 h) after FA. The epididymal tissues were taken for sperm analysing and the testes were removed for histological examination. In addition, testosterone levels were determined from the blood samples. Although the testosterone levels, the epididymal sperm concentration, and the progressive sperm motility significantly decreased, the abnormal sperm rate significantly increased in the Group II when compared to Group I. In the Group III, these damages were seen less. When the rats in the Group II compared with the control group, there were serious histological damages. In the Group III, it was determined that the histological changes were less than group II. It can be expressed that serious damages occurred via formaldehyde exposure in male reproductive system and that the rose oil had protective effects against these damages.     

Exposure to genistein during gestation and lactation demasculinizes the reproductive system in rats

PURPOSE: Exposure to the phytoestrogen genistein (Indofine Chemical Co., Somerville, New Jersey) can disrupt normal male sexual differentiation. To determine if perinatal (that is gestation and lactation) genistein exposure at doses common in human diets alters masculinization we examined the development of the external genitalia, testes, wolffian ducts and sexual behavior in male rats exposed to genistein supplemented diets during early development. MATERIALS AND METHODS: Female rats were fed a phytoestrogen-free diet supplemented with no genistein (free), a low genistein dose (low) or a high genistein dose (high) throughout gestation and lactation. Anogenital distance of male offspring was measured weekly from postnatal days 2 to 21. At puberty (postnatal day 40 to 45) preputial separation, and testis length and width of male offspring were measured. At age 70 days reproductive organ masses, plasma testosterone concentration, sperm counts and sexual behavior were assessed in male offspring.RESULTS Exposure to genistein resulted in temporary, prepubertal urogenital abnormalities at postnatal days 21 and 40. Males exposed to genistein had smaller anogenital distance and testis size, and delayed preputial separation. Perinatal exposure to genistein also caused long-term dysfunction in reproductive behavior, in which adult males exposed to genistein were less likely to mount, intromit and ejaculate during mating tests. Males exposed to genistein also had lower testosterone concentrations in adulthood. CONCLUSIONS: Perinatal genistein exposure results in transient and lasting alterations in masculinization of the reproductive system. These results extend our knowledge of the effects of early genistein exposure on male development and may have implications for human health in terms of potential relationships of endocrine disrupters and urogenital abnormalities thought to be increasing in incidence in boys and men.     

Dose‐ and time‐dependent effects of Garcinia kola seed extract on sexual behaviour and reproductive parameters in male Wistar rats

The aim of the present study was to investigate the effects of a crude extract of Garcinia kola on male sexual function after subchronic and chronic treatment periods at different sublethal doses. Adult male Wistar rats were treated orally with 100, 200 and 400 mg kg^?1 of a 70% ethanolic extract of G. kola daily for 56 days. Sexual behaviour studies were performed on days 28 and 50. At termination on day 56, organ weights, sperm count, reproductive hormone levels and testicular histology were assessed. Subchronic and chronic treatment of normal male rats with G. kola extract resulted in overall increase in components of libido, erection and ejaculation in treated rats – with lower doses being more efficient than the higher dose. There was a slight reduction in some components of sexual behaviour with prolonged time of treatment. G. kola treatment at all doses resulted in increased testicular weights, increased sperm count with no change in motility and increased serum testosterone levels with no change in gonadotropin levels. Gross testicular histology was not affected by treatment. We conclude that G. kola seed extract possesses potent aphrodisiac activity in male albino rats with resultant increase in sperm count and testosterone levels.     

Differences in Prepuberal Neonatally Estrogenized or Androgenized Male Rats

The main objective of this work was to analyze the different effects produced in prepuberal male rats by neonatal androgenization or estrogenization. For this purpose male Wistar rats were injected on day one of life with 500 micrograms of estradiol benzoate (estrogenized animals), 500 micrograms of testosterone propionate (androgenized animals) or olive oil (control animals) and decapitated on day 15. At the moment of decapitation estrogenized animals showed decreases in body, testes, prostate and adrenal weights, increases in pituitary, seminal vesicles and epididymis weights, an increase in prolactin plasma levels and a decrease in those of androgens. Androgenized animals showed only decreased testes and epididymis weights and androgen plasma levels. These results evidence the presence of important qualitative differences in prepuberal neonatally estrogenized or androgenized rats, especially in the accessory sex organs.     

Leptin secretion from the epididymal fat pad is increased by the sexual maturation of the male rat

Although leptin has been implicated as an important factor in triggering the onset of puberty in females, much less is known about the role of this adipose tissue hormone in the sexual maturation of males. Previous work in the rat has suggested that the peripubertal rise in testosterone precedes an increase in leptin secretion, and it has been suggested that the testosterone rise induces the leptin increase. These studies examined some of the interactions between leptin secretion and the peripubertal testosterone rise in male rats. Serum leptin concentrations were significantly elevated in young adult male rats compared with immature rats. Cultured epididymal fat pads obtained from adult animals secreted significantly more leptin than did those obtained from immature rats. Castration of immature rats with or without testosterone replacement for 1 week did not result in a significant change in either the serum leptin concentrations or the ability of the epididymal fat pad to secrete leptin. Exposure of epididymal fat to 5 ng/mL of testosterone in vitro resulted in a significantly enhanced secretion of leptin into the media compared with plain media controls. These results confirmed that there is an increase in serum leptin concentrations with sexual maturation in the male rat. They also suggest that this increase is due to an enhanced ability of adipose tissue to secrete leptin. Within a normal physiologic range, testosterone may play a role in inducing this increased ability to secrete leptin.     

Recovery of lead‐induced suppressed reproduction in male rats by testosterone

The objective of the present study was to investigate the effects of testosterone in recuperation of lead‐induced suppressed reproduction in adult male rats. Lead acetate was administered orally to adult male rats (95 ± 5 days) at dosage level of 0.05 and 0.15% for 55 days through drinking water and injected intraperitoneally with either testoviron depot at a dose of 4.16 mg kg^?1 body weight or vehicle alone on days 1, 7 and 14 respectively. At the end of treatment, control and treated males were cohabited with untreated normal‐cycling females. After cohabitation for 5 days, all the male rats were killed and weights of reproductive organs were determined. Significant increase in the indices of testis, epididymis, seminal vesicles, vas deferens and prostate glands was observed in testosterone (T)‐treated rats when compared to those of lead‐exposed rats. Testosterone treatment significantly increased epididymal sperm count, motile spermatozoa, viable spermatozoa and HOS tail‐coiled spermatozoa and also the activity levels of testicular 3β‐ and 17β‐hydroxysteroid dehydrogenases when compared to those of lead‐exposed males. From the results, it can be hypothesised that supplementation of testosterone mitigated lead‐induced suppressed reproduction in male rats.     

Exposure of juvenile rats to the phytoestrogen daidzein impairs erectile function in a dose-related manner in adulthood

Health benefits of isoflavones such as genistein and daidzein have led to an increasing interest in consuming soybeans or soy-containing food. However, possible adverse effects of such plant estrogens on the male reproductive system, particularly penile erection, have not been sufficiently evaluated. In previous research, we observed that exposure of adult rats to daidzein could attenuate apomorphine-induced erections. To identify the impact of daidzein exposure in early life on erectile function, we evaluated erectile capacity using an apomorphine-induced erectile test and determining intracavernous pressure after exposure of juvenile rats to daidzein at a dose of 2, 20, or 100 mg/kg for 90 days. Meanwhile, the levels of sex hormones, including testosterone, luteinizing hormone, and follicle-stimulating hormone, were determined. Both subtypes of the estrogen receptor (alpha and beta) in the corpora cavernosa were also detected immunohistochemically. When the rats were examined at adulthood, we observed that those animals treated with a medium (20 mg/kg) or high (100 mg/kg) dose of daidzein, but not with a low dose (2 mg/kg), showed lower plasma testosterone levels and attenuated erectile parameters, including apomorphine-induced erections and intracavernous pressure concomitant with markedly decreased expression of estrogen receptor beta in the corpora cavernosa. However, the penis still grew to its normal size, as in controls. Thus, these results suggested that exposure of juvenile rats to daidzein in a relatively large amount could adversely affect penile erection in adulthood.     

Carbamazepine damage to rat spermatogenesis in different sexual developmental phases

Carbamazepine (CBZ) is a first-line antiepileptic drug (AED), although it is also utilized for treatment of psychiatric disorders and neuropathic pain. The utilization of CBZ has been associated with damage to male reproduction including hormonal alterations, sexual dysfunction and reduction of sperm quality. Wide and long-term use of CBZ has been a common schedule for children and adolescents, despite the fact it alters the testosterone level in adult rats and humans. In addition, hypothalamic-pituitary-gonadal (HPG) axis during pre-puberty and puberty is more susceptible to toxic agents than in adult phase. The objective of this work was to evaluate the side effects of CBZ on the spermatogenic process of rats from pre-puberty to puberty and sexual maturation. Damage on the seminiferous epithelium, testicular interstitial oedema, reductions of testosterone levels and an increase in oestradiol levels were observed in rats, which were CBZ-treated since the weaning. The results suggest that CBZ, when administered from pre-puberty, provokes specific side effects on rat testes, resulting in more severe damage in the adult phase.     

Butyl paraben-induced changes in DNA methylation in rat epididymal spermatozoa

Parabens have been shown to affect male rodent reproductive parameters, including testosterone levels and sperm production. In this study, we examined the effect of long-term exposure to butyl paraben (BP) on rat epididymal sperm DNA methylation. Adult male rats were exposed to BP (0, 10, 100 and 1000 mg kg(-1) per day) according to OECD TG407 for a repeated 28-day oral toxicity study. Sperm DNA methylation was examined by differential display random amplification of polymorphic DNA (RAPD) following methylation-specific restriction digestion of DNA. Among the 57 RAPD amplicons, six were methylation specific. Of these, five amplicons increased by 1.4- to 3.8-fold in epididymal sperm DNA at testing dose of BP. This indicates that BP can cause DNA hypermethylation in germ cells from the mitotic through post-meiotic stage in adult rat testes. To our knowledge, this is the first report on the epigenetic modification of sperm DNA by parabens.     

Successful lowering of epididymal carnitine by administration of pivalate to rats

This study was designed to lower the epididymal content of carnitine in male rats and to examine subsequent effects on fertility and sperm motility. As carnitine is transported from serum into the epididymal lumen a method to lower serum carnitine was sought. Administration of 20 mmol/L sodium pivalate in the drinking water for up to 5 weeks substantially lowered serum carnitine (to 20% of control levels within 1 week) and reduced epididymal carnitine content (to 25% of control levels in the proximal and 52% of control in distal regions) within 2 weeks. Carnitine in distal cauda epididymal fluid was also reduced (to 30% of control levels) but no changes were observed in the sperm carnitine content. The percentage motility and kinematic parameters of spermatozoa released from four epididymal regions and diluted into artificial medium were unaltered by the treatment, and all males retained their fertility in mating tests performed at weekly intervals. Increasing the dose of sodium pivalate administered to 60 mmol/L for 2 weeks lowered serum carnitine concentration more but did not further decrease epididymal carnitine content and altered neither sperm motility nor male fertility. The rat epididymis secretes an excessive amount of carnitine into its lumen so that substantially lowering the tissue content does not reduce sperm carnitine or affect their motility or fertilizing ability.     

大豆黄酮对小鼠精子质量、睾丸重量及睾酮水平的影响

目的 :探讨大豆黄酮对小鼠精子质量、睾丸生长和睾酮水平的影响。　方法 :给雄性小鼠饲喂 3个不同剂量的大豆黄酮 ( 5、10 0、10 0 0mg/kg日粮 ) ,2 1d后宰杀 ,睾丸称重 ,伊红丫染色确定精子存活率 ,顶体染色采用姬姆萨染色法 ,睾酮浓度采用放射免疫法测定。　结果 :5mg/kg日粮大豆黄酮能显著提高睾酮分泌水平 (P <0 .0 1) ,睾丸明显增重 (P <0 .0 5 ) ,提高了精液质量 ;10 0 0mg/kg日粮大豆黄酮抑制睾酮的分泌 (P <0 .0 1) ,精液质量变化不明显 ;10 0mg/kg日粮的大豆黄酮对精子质量等指标均无显著影响。　结论 :大豆黄酮能影响小鼠精子质量、睾丸生长及睾酮水平 ,并与剂量有关     

Effects of α-Interferon on Sperm Production, Concentration, and Motility in the Rat

Background :
We evaluated possible effects of α-interferon (α-IFN) on testicular spermatogenesis and epididymal sperm quality in the nude rat.
Methods :
Nude male rats were administered subcutaneous injections of human α-IFN daily for 3 months. The luminal content of the cauda epididymidis was collected by micropuncture. Daily sperm production was determined by Amann's method and sperm concentrations were determined by microassay. Progressive motility was judged by evaluating the linear distance traveled by the sperm in a diluent. Serum levels of testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were also measured at the end of the experiment.
Results :
Daily sperm production and epididymal sperm concentrations were significantly increased after administration of α-IFN, while progressive motility of the spermatozoa was not altered. α-IFN significantly increased serum testosterone levels, while it decreased serum LH levels and left serum FSH levels unchanged.
Conclusion :
α-IFN may improve testicular spermatogenesis and increase the epididymal sperm concentration in the rat. These promising results with α-IFN may pave the way for a new approach to treating male infertility.     

Effect of alcoholic extract of Lepidium meyenii （Maca） on testicular function in male rats

Aim: To evaluate the effect of the alcoholic extract of Lepidium meyenii (Maca) on the spermatogenesisin male rats. Methods: In Holtzman rats, Maca alcoholic extract (5 %) was given by oral route at doses of 48 mg/day or 96 mg/day for 7 days, 14 days and 21 days. Testicular function was assessed by measurements of lengths of different stages of seminiferous epithelia and by epididymal sperm count. Results: Ethanolic extract of Maca increased the length of stages IX-XI of seminiferous epithelium at treatment day 7, day 14 and day 21. Progression of spermatogenesis was evident only after day 21 when lengths of stages XII-XIV of seminiferous epithelium were increased; at day 7 and day 14, no important change in spermatogenesis was observed. Epididymal sperm count was increased with 48 mg/day at all times. With 96 mg/day an increase in sperm count was observed at day 7, but it was reduced at day 14 and day 21 of treatment. Serum testosterone levels were not affected. Conclusion: The alcoholic extract of Maca activates onset ant progression of spermatogenesis at 48 mg/day or 96 mg/day in rats.     

Combination of running exercise and high dose of anabolic androgenic steroid,nandrolone decanoate,increases protamine deficiency and DNA damage in rat spermatozoa

High doses of anabolic‐androgenic steroids (AAS) are used by some athletes to increase muscle mass, that is often associated with male infertility. The aim of this study was to investigate the possible cause/s of male infertility using a rat model by analysing sperm quality, including its protamine content and DNA integrity, as well as pregnancy rate. Five groups of male Wistar rats were treated for 10 weeks as follows: nandrolone decanoate (10 mg kg^?1 per week) (ND); running exercise (50 min per day, 5 days a week) (EX); Combination of ND and exercise (ND‐EX); nandrolone decanoate solvent (Sham); and control without any injection or exercise (CO). Deterioration in sperm quantity was observed in all test groups (P ≤ 0.01). The frequency of fertile rats was decreased in the ND‐EX and ND groups (P ≤ 0.05). Chromomycin‐A3 staining showed a protamine deficiency in the epididymal spermatozoa in the ND‐EX rats (P ≤ 0.05). Chromatin analysis indicated an abnormal maturation of the sperm nuclei in all test groups compared with the controls (P ≤ 0.05). TUNEL analyses showed a highly significant increase in apoptosis in the EX, ND, and ND‐EX groups (P ≤ 0.01). Our data show that a combination of exercise and high doses of nandrolone decanoate negatively influences the DNA integrity and protamine content resulting in lower sperm quality and reduced pregnancy rate.     

Ablation of the inferior mesenteric plexus in the rat: alteration of sperm storage in the epididymis and vas deferens

The involvement of the sympathetic nervous system in the transport and storage of spermatozoa in the male reproductive tract was examined by surgically ablating the inferior mesenteric plexus (IMP). One to eight weeks after ablation of the IMP, epididymal weight and the total number of spermatozoa present in the cauda epididymidis were significantly greater in IMP-ablated rats than in sham-operated rats. By contrast, the number of spermatozoa present in the initial segment of the vas deferens was significantly greater than in sham operated controls one week after IMP ablation but returned to control levels at two, four, six and eight weeks. Throughout the experiment, no differences were observed between IMP-ablated and control rats in the percentage of motile cauda epididymal spermatozoa, testicular weight, testicular sperm number or serum testosterone. These data demonstrate that the sympathetic nervous system differentially regulates sperm transport and storage in the male reproductive tract and suggest that the IMP may influence the epididymal maturation of spermatozoa.     

Serum levels and metabolic clearance of the isoflavones genistein and daidzein in hemodialysis patients

Genistein and daidzein are biologically active isoflavones that are especially abundant in soybeans. After intestinal absorption, circulating genistein and daidzein are eliminated primarily by the kidneys. This study was undertaken to assess the metabolism of genistein and daidzein in patients with end-stage renal disease (ESRD) on hemodialysis therapy, and to test whether this treatment modality can replace the lack of kidney function, with respect to the elimination of the isoflavones. Twenty-three hemodialysis patients and 10 healthy subjects were studied. While consuming a self-selected low isoflavone diet, baseline blood levels were undetectable in eight of 10 healthy subjects and in 14 of 23 dialysis patients. The remaining participants had detectable levels, with the nine dialysis patients displaying much higher blood concentrations than the two healthy control subjects. After the evening intake of one dose of an isoflavone-rich soy protein isolate drink, the early morning blood levels of genistein and daidzein were higher in seven dialysis patients than in eight healthy subjects (genistein 1271+/-321 versus 425+/-104, P<0.05; daidzein 1304+/-352 versus 292+/-78, P<0.05). The blood clearance of the isoflavones was studied in two healthy subjects and in three dialysis patients. Genistein and daidzein were eliminated within 2 d in the healthy subjects, but had not returned to baseline in two of three ESRD patients, 7 d after intake. The half-life of both compounds was estimated to be 10-fold longer in the ESRD patients than in the healthy subjects. Finally, genistein and daidzein levels were measured before and after dialysis in five patients, both while on their regular diet and after one dose of a soy protein isolate drink. In both instances, the dialysis treatment did not affect the blood isoflavone levels. In conclusion, approximately one-third of hemodialysis patients eating the standard American renal diet experience high blood levels of the isoflavones genistein and daidzein, while the remaining two-thirds have undetectable levels. After ingestion of isoflavone-rich food such as soy products, all patients have detectable levels that remain very high for several days due to lack of renal excretion.     

Gallic acid protects against cyclophosphamide‐induced toxicity in testis and epididymis of rats

The protective role of gallic acid (GA) on reproductive toxicity induced by cyclophosphamide (CPA), an antineoplastic drug, was investigated in male Wistar rats. Sixty rats were grouped into 10 rats per group. Group 1 (control) received distilled water. Rats in groups 2 and 3 received GA alone at 60 and 120 mg kg^?1 for 14 consecutive days, respectively. Group 4 received a single intraperitoneal dose of CPA at 200 mg kg^?1 on day 1. Groups 5 and 6 received a single dose of CPA (200 mg kg^?1) intraperitoneally on day 1 followed by treatment with GA at 60 and 120 mg kg^?1 for 14 consecutive days, respectively. In testes and epididymis of the treated rats, CPA administration resulted in significant elevation (P < 0.05) in malondialdehyde (MDA), nitrite and hydrogen peroxide levels. There was a significant decrease in the activities of superoxide dismutase and glutathione‐S‐transferase. Furthermore, there were significant reductions in plasma luteinising hormone (LH), follicle stimulation hormone (FSH) and testosterone levels, which were accompanied by significant decrease in sperm motility and viability in CPA‐treated rats. Histological examination revealed marked testicular and epididymal atrophy in CPA alone treated rats and these aberrations were reversed by GA. In conclusion, GA has capacity to protect against reproductive toxicity induced by cyclophosphamide.