Genital Psoriasis: Impact on Quality of Life and Treatment Options.

Psoriasis involving the genital skin occurs in up to two-thirds of psoriasis patients but is often overlooked by physicians. Furthermore, psoriasis objective and subjective severity indexes for common plaque psoriasis often neglect the impact this small area of psoriasis can have on a patient. It can have a significant impact on patients' psychosocial function due to intrusive physical symptoms such as genital itch and pain, and a detrimental impact on sexual health and impaired relationships. The mainstay of treatment is topical therapy. In patients with genital psoriasis refractory to traditional topical treatment, biologic treatments may greatly improve patient outcomes.

Potential of hyperbaric oxygen in urological diseases.

Hyperbaric oxygen therapy is a promising medical technology that delivers oxygen to targeted tissues at high pressure to increase the amount of dissolved oxygen in the blood. Over the past three decades, hyperbaric oxygen has been used in a variety of conditions, including radiation-induced tissue injuries, non-healing states with ischemia and malignant neoplasms. In the field of urology, hyperbaric oxygen has also been applied to some pathological conditions (e.g. radiation-induced hemorrhagic cystitis, Fournier gangrene, interstitial cystitis, male infertility, acute kidney injury and urological cancers). In normal and injured tissues, hyperoxia from hyperbaric oxygen therapy contributes to anti-inflammation, angiogenesis through endothelial proliferation, enhanced fibroblastic activity, increased lymphocyte and macrophage activity, and bactericidal effects with the aim of wound repair. In cancerous tissues, the enhanced supply of oxygen into the hypoxic cancer cells can exert inhibitory effects on factors that contribute to their aggressiveness (e.g. cell survival, escape from apoptosis, epithelial-to-mesenchymal transition and tumor immunotolerance), and sensitize the tumor to radiation therapy and chemotherapy. However, further research, including multicenter clinical studies, is essential for determining the role of hyperbaric oxygen therapy in refractory urological diseases that are resistant to conventional therapies.

CBLB502, a Toll-like receptor 5 agonist, offers protection against radiation-induced male reproductive system damage in mice.

CBLB502, a Toll-like receptor (TLR)5 agonist derived from Salmonella flagellin, was shown to protect mammalian hematopoietic and gastrointestinal systems from acute irradiation syndrome and to stimulate regeneration. To explore whether CBLB502 can improve testicular injuries caused by irradiation, mice were intraperitoneally injected with 0.2 mg/kg CBLB502 or vehicle control 30 min prior to applying 5.0 Gy ionizing radiation (IR). We observed these mice for the following 120 days and determined that CBLB502 pretreatment alleviated IR-induced oxidative stress, alleviated the distorted architecture of seminiferous tubules, reversed the decline of sperm quantity and quality, and helped recover male mouse fertility. Additionally, CBLB502 efficiently reduced DNA damage and chromosomal aberrations in IR-treated mice and their offspring. Due to the suppression of p53-dependent apoptosis, in IR-treated mice, CBLB502 was shown to significantly activate the nuclear factor kappa B (NFκB) pathway and reduce the apoptotic rate in association with an increase in anti-apoptotic B-cell lymphoma 2 levels and a decrease in the levels of DNA repair protein and proliferating cell nuclear antigen. Moreover, an IR-induced reduction in serum testosterone and superoxide dismutase levels and an increase in malondialdehyde levels were considerably reversed in CBLB502-pretreated mice. No significant reverse effects were found in Tlr5 knockout mice, suggesting that protection of the testis against IR by CBLB502 is primarily dependent on the TLR5 signaling pathway. Our results may help further investigations into potential CBLB502 applications for the protection of the male reproductive system during radiotherapy.

Protective effect of Nigella sativa oil against acetamiprid induced reproductive toxicity in male rats.

The present study was designed to investigate the adverse reproductive effects of acetamiprid, besides the possible protective role of Nigella sativa oil (NSO), as a potential antioxidant agent. Thirty-two male Wistar rats were allocated into four equal groups of eight, control (CRL), acetamiprid (ACMP, 27 mg/kg), Nigella sativa oil (NSO, 0.5 ml/kg) and in combination (ACMP + NSO). The experimental animals were dosed by gavage (5 days per week) for 45 consecutive days. Body weight gain, reproductive organs weights, sperm characteristics, testosterone, and thiobarbutiric acid-reactive substances (TBARS) levels were investigated. The obtained results showed that ACMP decreased significantly (p < 0.001) the body weight gain and the absolute weights of reproductive organs (testes, epididymis, and seminal vesicles). Furthermore, significant alterations at least (p < 0.01) in semen characteristics were noted in ACMP group as evidenced by a decline in spermatids number, sperm count, sperm motility, and testosterone level with an increase in abnormal and dead sperm and TBARS level. Treatment with NSO alone may stimulate spermatogenesis, increased significantly (p < 0.001) spermatids number and the weight of seminal vesicles. On the other hand, the co-administration of NSO along with ACMP can mitigate more efficiently and modulate in certain cases the adverse effects induced by ACMP on reproductive organs weights, semen quality, testosterone, and TBARS levels (at least p < 0.001). This obvious protective role of NSO against ACMP induced reproductive toxicity may be due to its antioxidant properties and ability to reduce TBARS levels as shown in this work.

Momordica cochinchinensis (L. ) spreng: aril extract prevents adverse reproductive parameters of male rats Induced with valproic acid / El extracto del arilo Momordica cochinchinensis (L. ) Spreng previene los parámetros reproductivos adversos inducidos con ácido valproico en ratas macho

This study aimed to investigate protective effect of Momordica cochinchinensis (MC) aril extract on adverse reproductive parameters of male rat induced with valproic acid (VPA) commonly used in treatment for antiepileptic diseases. Male Wistar rats were divided into 6 groups (control, VPA, 200 mg/kg BW of PE only, and 50, 100, 200 mg/kg BW MC+VPA, respectively). Animals were pretreated with aqueous MC extract for 23 days before co-administered with VPA induction for 10 days. At the end of experiment, all male reproductive parameters and testicular histology were examined. The results showed all doses of PE significantly protect the decrease the weights of epididymis and seminal vesicle but not of body and testicular weights. MC extract also increased sperm concentration and seminiferous tubular diameters in MC+VPA co-administrative groups. Moreover, testicular histology of MC+VPA groups showed significant declining of testicular histopathologies as compared to VPA group. It was concluded that M. Cochinchinensis aril extract can prevent adverse male reproductive parameters and testicular damage induced with VPA.

El objetivo fue investigar el efecto protector del extracto de arilo de Momordica cochinchinensis (MC) sobre los parámetros reproductivos adversos de la rata macho inducida con ácido valproico (AV) que se utiliza comúnmente en el tratamiento de enfermedades epilépticas. Las ratas se dividieron en 6 grupos (control, AV, 200 mg/kg por peso corporal de PE solamente, y 50, 100, 200 mg/kg por peso corporal MC+AV, respectivamente). Los animales fueron tratados previamente con extracto acuoso MC durante 23 días, antes de la administración de AV durante 10 días. Al término del experimento, se examinaron todos los parámetros reproductivos masculinos y la histología testicular. Los resultados indicaron que todas las dosis de PE protegen de manera significativa la disminución de los pesos de epidídimo y vesículas seminales, pero no de peso corporal y testicular. El extracto de MC también aumentó la concentración de espermatozoides y los diámetros de los túbulos seminíferos en los grupos de administración con MC+AV. Por otra parte, la histología testicular de los grupos MC+AV mostró una disminución significativa de histopatologías testiculares en comparación con el grupo AV. En conclusión, el extracto de arilo M. cochinchinensis puede prevenir la aparición de parámetros reproductivos masculinos negativos y los daños testiculares inducidos con AV.

Biphasic effect of Syzygium aromaticum flower bud on reproductive physiology of male mice.

The flower buds of Syzygium aromaticum (clove) have been used for the treatment of male sexual disorders in indigenous medicines of Indian subcontinent. Therefore to evaluate the efficacy of Syzygium aromaticum on the male reproductive health, chronic oral exposure of aqueous extract of flower buds of Syzygium in three doses (15 mg, 30 mg and 60 mg kg-1 BW) were studied for a single spermatogenic cycle (35 days) in Parkes (P) strain mice. Lower dose (15 mg) of Syzygium aromaticum flower buds increased serum testosterone level and testicular hydroxysteroid dehydrogenase (HSD) activities and improved sperm motility, sperm morphology, secretory activity of epididymis and seminal vesicle, and number of litters per female. On the other hand, higher doses (30 and 60 mg) of the treatment adversely affected above parameters. Further, higher doses of the extract also had adverse effects on daily sperm production, 1C cell population and on histology of testis. In conclusion, Syzygium aromaticum flower buds extract exhibits biphasic effect on reproductive physiology of male mice. Lower dose of Syzygium aromaticum flower bud extract is androgenic in nature and may have a viable future as an indigenous sexual rejuvenator, while higher doses adversely affected functional physiology of reproductive organs.

Cuerpos extraños en pene / Penile foreign bodies

No disponible

Effect of honey on the reproductive system of male rat offspring exposed to prenatal restraint stress.

Exposure to prenatal stress is associated with impaired reproductive function in male rat offspring. Honey is traditionally used by the Malays for enhancement of fertility. The aim of this study was to determine the effect of honey on reproductive system of male rat offspring exposed to prenatal restraint stress. Dams were divided into four groups (n = 10/group): control, honey, stress and honey + stress groups. Dams from honey and honey + stress groups received oral honey (1.2 g kg(-1) body weight) daily from day 1 of pregnancy, meanwhile dams from stress and honey + stress groups were subjected to restraint stress (three times per day) from day 11 of pregnancy until delivery. At 10 weeks old, each male rat offspring was mated with a regular oestrus cycle female. Male sexual behaviour and reproductive performance were evaluated. Then, male rats were euthanised for assessment on reproductive parameters. Honey supplementation during prenatal restraint stress significantly increased testis and epididymis weights as well as improved the percentages of abnormal spermatozoa and sperm motility in male rat offspring. In conclusion, this study might suggest that supplementation of honey during pregnancy seems to reduce the adverse effects of restraint stress on reproductive organs weight and sperm parameters in male rat offspring.

GnRH Neuron-Specific Ablation of Gαq/11 Results in Only Partial Inactivation of the Neuroendocrine-Reproductive Axis in Both Male and Female Mice: In Vivo Evidence for Kiss1r-Coupled Gαq/11-Independent GnRH Secretion.

The gonadotropin-releasing hormone (GnRH) is the master regulator of fertility and kisspeptin (KP) is a potent trigger of GnRH secretion from GnRH neurons. KP signals via KISS1R, a Gαq/11-coupled receptor, and mice bearing a global deletion of Kiss1r (Kiss1r(-/-)) or a GnRH neuron-specific deletion of Kiss1r (Kiss1r(d/d)) display hypogonadotropic hypogonadism and infertility. KISS1R also signals via ß-arrestin, and in mice lacking ß-arrestin-1 or -2, KP-triggered GnRH secretion is significantly diminished. Based on these findings, we hypothesized that ablation of Gαq/11 in GnRH neurons would diminish but not completely block KP-triggered GnRH secretion and that Gαq/11-independent GnRH secretion would be sufficient to maintain fertility. To test this, Gnaq (encodes Gαq) was selectively inactivated in the GnRH neurons of global Gna11 (encodes Gα11)-null mice by crossing Gnrh-Cre and Gnaq(fl/fl);Gna11(-/-) mice. Experimental Gnaq(fl/fl);Gna11(-/-);Gnrh-Cre (Gnaq(d/d)) and control Gnaq(fl/fl);Gna11(-/-) (Gnaq(fl/fl)) littermate mice were generated and subjected to reproductive profiling. This process revealed that testicular development and spermatogenesis, preputial separation, and anogenital distance in males and day of vaginal opening and of first estrus in females were significantly less affected in Gnaq(d/d) mice than in previously characterized Kiss1r(-/-) or Kiss1r(d/d) mice. Additionally, Gnaq(d/d) males were subfertile, and although Gnaq(d/d) females did not ovulate spontaneously, they responded efficiently to a single dose of gonadotropins. Finally, KP stimulation triggered a significant increase in gonadotropins and testosterone levels in Gnaq(d/d) mice. We therefore conclude that the milder reproductive phenotypes and maintained responsiveness to KP and gonadotropins reflect Gαq/11-independent GnRH secretion and activation of the neuroendocrine-reproductive axis in Gnaq(d/d) mice. SIGNIFICANCE STATEMENT: The gonadotropin-releasing hormone (GnRH) is the master regulator of fertility. Over the last decade, several studies have established that the KISS1 receptor, KISS1R, is a potent trigger of GnRH secretion and inactivation of KISS1R on the GnRH neuron results in infertility. While KISS1R is best understood as a Gαq/11-coupled receptor, we previously demonstrated that it could couple to and signal via non-Gαq/11-coupled pathways. The present study confirms these findings and, more importantly, while it establishes Gαq/11-coupled signaling as a major conduit of GnRH secretion, it also uncovers a significant role for non-Gαq/11-coupled signaling in potentiating reproductive development and function. This study further suggests that by augmenting signaling via these pathways, GnRH secretion can be enhanced to treat some forms of infertility.

The effect of Lycium barbarum polysaccharides on the male rats׳ reproductive system and spermatogenic cell apoptosis exposed to low-dose ionizing irradiation.

ETHNOPHARMACOLOGICAL RELEVANCE: Lycium barbarum, a Solanaceous defoliated shrubbery, has been used as a kind of traditional Chinese herbal medicines for thousands of years. Lycium barbarum polysaccharide (LBP) is the main bioactive component of Lycium barbarum. The aim of this study was to investigate the radioresistant effect of LBP on the damage of male rats' reproductive system and spermatogenic cells caused by low-dose (60)Co-γ irradiation. MATERIALS AND METHODS: Male rats were randomly divided into 7 groups and treated with irradiation and/or LBP: normal control group, irradiation control group 1, irradiation control group 2, irradiation control group 3, LBP + irradiation group 1, LBP + irradiation group 2, and LBP + irradiation group 3. RESULTS: It is found that mating function and testis organ coefficient in LBP + irradiation groups were significantly better than that of the corresponding irradiation control groups. LBP significantly up-regulates the expression of Bcl-2 while down-regulating the expression of Bax. And LBP also plays an important role in prevention mitochondrial membrane potential decrease. In addition, LBP can significantly reduce spermatogenic cells apoptosis. CONCLUSION: LBP has obvious protective effect on the male rats' reproductive function and spermatogenic dysfunction induced by irradiation.

Protective effect of vitamin E and selenium combination on deltamethrin-induced reproductive toxicity in male rats.

The current study was performed to assess the adverse effect of deltamethrin (DLM) on reproductive organs and fertility in male rats and to evaluate the protective role of vitamin E (VE) and selenium (Se) combination in alleviating the detrimental effect of DLM on male fertility. The lethal dose 50 (LD(50)) of DLM for male rats was estimated at 6 mg/kg bwt. Thirty male albino rats (10-weeks-old) were divided into three groups (10 rats each): Control group was injected subcutaneously with 2 ml/kg bwt saline twice weekly and was daily administered 2 ml distilled water intra-gastrically; DLM-treated group received 0.6 mg/kg bwt (1/10 LD(50)) DLM intra-gastrically once daily; DLM+VE/Se-treated group was injected subcutaneously with 1.2 mg/kg bwt Viteselen(®)15 (VE/Se) twice weekly with concurrent daily administration of 0.6 mg/kg bwt (1/10 LD(50)) DLM intra-gastrically. The experiment was conducted for 60 consecutive days. DLM caused a significant reduction in reproductive organs weights, sperm count, sperm motility percent, alive sperm percent, serum testosterone level and testicular reduced glutathione concentration (GSH). DLM-treated group showed a significant increase in sperm abnormalities and testicular malondialdehyde (MDA) concentrations. Histopathologically, DLM caused impairments in testes, epididymes and accessory sex glands. Conversely, treatment with VE/Se combination improved the reduction in the reproductive organs weights, sperm characteristics, DLM-induced oxidative damage of testes and the histopathological alterations of reproductive organs. Results indicate that DLM exerts significant harmful effects on male reproductive system and that the concurrent administration of VE/Se partly reduced the detrimental effects of DLM on male fertility.

The effect of Laminaria japonica polysaccharides on the recovery of the male rat reproductive system and mating function damaged by multiple mini-doses of ionizing radiations.

To evaluate the radiation-protect effects of Laminaria japonica polysaccharides (LJP) on male reproductive system damage and mating dysfunction induced by multiple mini-dose ionizing radiations, male rats were administrated with radiation and/or LJP. Results showed that mating function (such as erection, mount and ejaculation), sperm count and survival rate in LJP group were significantly better than the corresponding model group after the radiation. The testis organ coefficient, GSH (glutathione) content, serum sex hormones (luteinizing hormone, follicle-stimulating hormone, testosterone and estradiol) levels improved while MDA (malondialdehyde) content decreased. In addition, SOD (superoxide dismutase), GSH-PX (glutathione peroxidase), LDH (lactate dehydrogenase) activities were enhanced while testicular tissue damage was reduced, 14 days after the cessation of radiation; all indicators in the LJP group were similar to the control group. Our results suggest that, LJP has some promoting effects on the recovery of the reproductive system and mating dysfunction induced by radiation.

The interactive effect of dietary fat-soluble vitamin levels on the depression of gonadal development in growing male rats kept under disturbed daily rhythm. Investigations based on the L16(2¹5) type orthogonal array.

The purpose of this study was to clarify the effects of nutrients on the gonadal development of male rats kept under constant darkness as a model of disturbed daily rhythm. In the present study we examined fat-soluble vitamins and their interactions in this test population. Four fat-soluble vitamins (vitamin A (V.A), vitamin D (V.D), vitamin E (V.E) and vitamin K (V.K)) were selected as experimental factors, and the dietary content of these vitamins was normal (AIN-93G) or three times the normal content. Lighting conditions (constant darkness or normal lighting) were also added as a factor. Four-week-old rats (Fischer 344 strain) were kept under constant darkness or normal lighting (12-h light/dark cycle) for 4 wk. The lighting condition and V.E, and the interactions between the lighting condition and V.E and between V.A and V.D were observed to affect the testes and epididymides weights. There was an influence of the lighting condition only on the seminal vesicles and prostate weights and the serum testosterone concentration. Among the constant darkness groups (D-groups), the highest value for testes weight was observed under the normal-V.A, normal-V.D and high-V.E diet. The interaction between lighting condition and V.E showed the testes weight increased slightly in response to changing to a high-V.E diet from a normal-V.E diet under normal lighting (N-group) but was greatly increased in response to this change in the D-group. It became clear that the amount of dietary V.E necessary for the gonadal development of rats increases when rats are kept under constant darkness.

The effect of dietary supplementation with limonene or myo-inositol on the induction of neoplasia and matrix metalloproteinase and plasminogen activator activities in accessory sex organs of male Lobund-Wistar rats.

Prostate cancer, the most prevalent non-cutaneous cancer in men, is associated with increased age. This suggests that dietary chemopreventive measures could be effective in delaying the onset or decreasing the severity of the disease. We utilized the Lobund-Wistar rat nitrosomethylurea induced, testosterone promoted (NMU-T) model of male sex accessory gland cancer to test the potential chemopreventive effects of myo-inositol and limonene on tumor incidence and associated protease activities. Tumors were found to arise in the seminal vesicles and dorsal and anterior prostate lobes. There were also some tumors that appeared to arise in both the seminal vesicles and anterior prostate, and in some cases the tissue of origin was not clear. The distribution of tumors as to site of origin in limonene or myo-inositol treated animals did not vary from that of the starch fed control animals, and the number of animals presenting with metastases did not vary significantly between treatment groups. There was a statistically significant delay in onset of tumors in myo-inositol, but not limonene fed rats, at 10 months post-induction of carcinogenesis; however, at 12 and 15 months this was not significant. The ventral prostate and seminal vesicles expressed pro-MMP-2 and plasminogen activator (PA) activities. Based on sensitivity to amiloride, the PA activities were predominately urokinase (uPA) in the ventral prostate and a mixture of tissue-type activator (tPA) and uPA in the seminal vesicles of non-treated rats. Sex accessory gland tumors, and metastases, expressed increased levels PA and pro- and active forms of MMP-2 and -9. The PA activities of the tumors were a mixture of uPA and tPA. There was no difference in the levels of these protease activities based on the tissue of tumor origin, nor in tumor vs metastasis. These studies indicate that MMP and PA activities play a role in sex accessory gland tumor biology and that dietary supplementation with myo-inositol can delay but not ultimately prevent the development of such tumors.

Disruption of testosterone homeostasis as a mode of action for the reproductive toxicity of triazole fungicides in the male rat.

Triazole fungicides associated with a range of reported male reproductive effects in experimental animals were selected to assess potential toxic modes of action. Wistar Han rats were fed myclobutanil (M: 100, 500, or 2000 ppm), propiconazole (P: 100, 500, or 2500 ppm), or triadimefon (T: 100, 500, or 1800 ppm) from gestation day 6 to postnatal day (PND) 120. One male per litter was necropsied on PND1, 22, 50, or 92. Measurements included anogenital distance (AGD) at PND0, body and organ weights, serum hormone levels, age at preputial separation (PPS), sperm morphology and motility, and fertility and fecundity. AGD was increased by the high dose of all three triazoles, indicating hypervirilization. Triadimefon delayed PPS, consistent with delayed puberty, at 1800 ppm. Relative liver weights were increased at PND1, 50, and 92 by all three triazoles. Hepatocellular hypertrophy was present at PND50 from propiconazole and triadimefon and at PND92 from all three high-dose triazole treatments. Relative pituitary weights were decreased at PND92 by middle- and high-dose myclobutanil treatment. Absolute testis weights were increased at PND1 by myclobutanil, at PND22 by myclobutanil and triadimefon, and at PND50 by propiconazole and triadimefon treatment. Relative ventral prostate weights were increased at PND92 by myclobutanil and triadimefon treatment. Serum testosterone was increased at PND50 by triadimefon and at PND92/99 by all three triazole treatments. Insemination and fertility were impaired by myclobutanil and triadimefon treatment. In addition to the reproductive system effects, total serum thyroxine levels were decreased at PND92 by high-dose triadimefon. These reproductive effects are consistent with the disruption of testosterone homeostasis as a key event in the mode of action for triazole-induced reproductive toxicity.

Induction of antifertility with lupeol acetate in male albino rats.

The present study was undertaken to evaluate the antifertility activity of the active principle, i.e. lupeol acetate, isolated from benzene extract of Alstonia scholaris in male albino rats. The treatment with lupeol acetate at the dose level of 10 mg/rat/day did not cause any significant change in the body weights, but significant reduction in the weight of reproductive organs, i.e. testes, epididymides, seminal vesicle and ventral prostate, was observed. Testicular sperm count, epididymal sperm count and motility were found significantly declined when compared with controls, which resulted in reduction of male fertility by 100%. Arrest of spermatogenesis was noted at various stages with production of primary spermatocytes (preleptotene and pachytene), secondary spermatocytes and step-19 spermatids were decreased by 52.36, 54.91, 55.67 and 69.65%, respectively. The seminiferous tubules appeared reduced in size by 24.62%. Cross-sectional surface area of Sertoli cells as well as their counts were found to be significantly depleted. Leydig cell nuclear area and number of mature Leydig cells were decreased by 27.65 and 35.47%. Biochemical parameters of tissues i.e. protein, sialic acid, glycogen and cholesterol content of testes and seminal vesicular fructose also showed significant reduction.

Subchronic and chronic safety studies with genistein in dogs.

Genistein is a phytoestrogen that occurs naturally in the diet, especially in soy-based foods. There is widespread interest in phytoestrogens as chemopreventive agents for a variety of diseases and cancers based on epidemiologic evidence. Although soy and its constituents, such as genistein, have been consumed at high levels in several Asian populations without apparent adverse effects, concern has been raised about potential adverse effects due to estrogenic and other activities. The subchronic and chronic safety of genistein were evaluated in the beagle dog including a 4-week study and a 52-week safety study with a 13 week interim sacrifice and a 4 week recovery period. In both studies at doses of 50, 150 and 500 mg/kg/day, genistein was well tolerated. In the 4 week study, except for an increase in uterine weights in female dogs at 500 mg/kg/day, there were no other treatment related findings. In the 52-week study, the primary effects of genistein were observed on the reproductive tract, which included for male dogs: reduced size and/or weight of the testes, epididymus and prostate of 2/2 dogs after 13 weeks of treatment and in 1/4 dogs after 52 weeks of treatment at 500 mg/kg/day. The histological changes observed in the affected dogs at 500 mg/kg/day indicated atrophy of the testes and prostate gland and absent spermatozoa in the epididymus. At the mid-dose of 150 mg/kg/day, although there was a reduction to a lesser extent in testes weight after 13, but not 52 weeks, there were no histopathological changes. In female dogs, the reproductive tract effects included increased uterine weight at 500 mg/kg/day after 13 weeks of treatment, but not after 52 weeks of treatment. There was also a small decrease in ovarian weights at 150 and 500 mg/kg/day after 13 weeks and at 500 mg/kg/day after 52 weeks of treatment. There were no histopathological correlates to the changes in organ weights in female dogs. In the 4-week recovery group dogs, no changes were observed in dogs previously treated for 52 weeks with 500 mg/kg/day of genistein. It is concluded that the administration of genistein to dogs for a period of 4-52 weeks was well tolerated and did not result in systemic toxicity. Effects of genistein on the reproductive tract at very high doses were functional in nature and are of a type that would be expected in view of the relatively weak estrogenic activity of genistein and were considered not adverse effects. In the 4-week study, the no observed adverse effect level (NOAEL) for genistein was considered to be >500 mg/kg/day and the no observed effect level (NOEL) was considered to be 150 mg/kg/day. For the 52-week study, the NOAEL is considered to be >500 mg/kg/day and the NOEL is considered to be 50 mg/kg/day.

Efficacy trial on the purified compounds of the seeds of Carica papaya for male contraception in albino rat.

The contraceptive efficacy and toxicological screening of the two principal compounds, MCP I and ECP I, isolated from the seeds of Carica papaya, in male albino rats at the standardized dose regimen, at 50 mg/kg b.w./day, for a period of 360 days and up to 90 days of treatment withdrawal have been reported. The body and organ weights, cauda epididymal sperm characteristics, androgen sensitive tissue biochemistry, reactive oxygen species and anti-oxidant defense system in the cauda epididymal microenvironment, histology and ultrastructure of testis and cauda epididymis, histology of seminal vesicle and prostate, toxicological investigations through routine hematology and serum clinical chemistry, sexual behaviour and fertility index have been studied. The results revealed that oral administration of MCP I and ECP I were equally effective, exhibiting complete inhibition of sperm motility following 90 days of treatment that coincided with a gradual and significant decline in cauda epididymal sperm density, percent viable spermatozoa and significant increase in sperm anomalies. Histology of testis of treated animals revealed degenerated germinal epithelium, vacuolization in Sertoli cells and proliferating germ cells and disturbances in spermatid differentiation. Spermatogonial stem cell reserves and Leydig cells appeared normal. Ultrastructure of the testis revealed vacuolization in the Sertoli cells and germ cells, loss of cytoplasmic characteristics in the Sertoli cells, nuclear degeneration and mitochondrial vacuolization in spermatocytes and spermatids. Leydig cells exhibited steroidogenic features. Cauda epididymis showed normal epithelial cell function. Absence of spermatozoa or disruption of spermatozoa clusters in the lumen were evident. Ultrastructure of cauda epididymis revealed normal secretory activity. Morphology of seminal vesicle and prostate of the treated animals were comparable to control animals. Serum testosterone, tissue biochemical and toxicological parameters remained unaffected. Fertility test revealed 100% efficacy. All the altered parameters showed sign of recovery following 90 days of treatment withdrawal. It is concluded that both MCP I and ECP I are equally effective in terms of contraceptive efficacy which is likely reversible and without adverse side effects.

Age-induced apoptosis in the male genital tract of the mouse.

We have examined the effects of ageing on the increase in apoptotic cells numbers in the male genital tract of the house mouse (Mus musculus). We have found that not all organs have the same response. There is an induction of apoptosis in both the epididymis and ventral prostate. However, seminal vesicles and other prostatic lobes remain unaffected. Apoptosis was assessed by several methods: TUNEL, detection of the active fragment of caspase-3 and the pattern of DNA fragmentation on agarose gels. This increase in apoptosis is related to the fall in testosterone levels, although there is only a partial decrease in androgen receptor (AR). AR is still present in all tissues and only moderately reduced in the epididymis and ventral prostate. A more intense increase of lipofuscin granules, which may be indicative of oxidative stress, occurred in these tissues. Finally, testosterone supplementation reverses the changes (both in apoptosis and lipofuscin content in the tissue), suggesting a role of androgens in these processes.

Effects of dietary isoflavone aglycones on the reproductive tract of male and female mice.

We assessed the effects of dietary consumption of soy isoflavone aglycones on the reproductive tract of sexually mature male and female mice. Isoflavone concentrates with a ratio of 10:1, 2:1 or 1:10 genistein:daidzein (G:D) were added to provide 120 mg total isoflavones/1800 Calories (approximately 40 mg/kg body weight) to diets having either casein/lactalbumin or soy protein isolate as the source of protein. After 16 weeks, mice were necropsied and gross and histopathologic assessments of uterus, vagina, testes and accessory sex glands were completed. Effects of the 10G:1D isoflavone concentrates were absent or minimal in females but in males included atrophy of accessory sex glands. In contrast, the 2G:1D and 1G:10D concentrates caused dramatic estrogenic effects in both male and female mice. Effects in females included endometritis and effects typical of estrogenic stimulation (i.e., uterine enlargement, keratinization of vaginal epithelium, increased height of endometrial surface epithelial cells, and uterine squamous metaplasia). Effects in males included reduced plasma testosterone concentrations, atrophy of seminiferous epithelium, atrophy of accessory sex glands, and squamous metaplasia of seminal vesicles. Some effects varied with protein source. We conclude that a diet containing approximately 40 mg/kg soy isoflavone aglycones with a genistein:daidzein ratio of 2:1 or less has marked estrogenic effects on the reproductive system of male and female mice.