Lack of effects on fertility and developmental toxicity of a quadrivalent HPV vaccine in Sprague‐Dawley rats

Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases, with approximately half of the HPV‐infected people being adolescents and young adults. A recently developed quadrivalent HPV vaccine, GARDASIL^®, has been shown to be highly effective in the prevention of a number of HPV‐mediated diseases. The objective of the present study was to evaluate the potential effects of the vaccine on female fertility and F1 development, growth, behavior, and reproductive performance. In addition, anti‐HPV antibodies in the F0 females and F1 offspring were measured during the study. Two groups of 65 virgin Sprague‐Dawley rats were administered two or four intramuscular injections of the vaccine (full human dose of 0.5 mL at 5 and 2 weeks prior to mating, on Gestation Day [GD] 6, and Lactation Day [LD] 7; or GD 6 and LD 7 only). Additional groups of rats were administered phosphate‐buffered saline or Merck Aluminum Adjuvant (MAA) at the same four times. All females were mated to males of the same stock. Cesarean sections were performed on 22/group on GD 21, 22/group were allowed to deliver, and remaining females used for blood collections or replacements. F0 female fertility parameters were evaluated. An extensive number of prenatal, perinatal, and postnatal parameters were evaluated in the F1 generation. There were no unscheduled deaths during the study. There was no evidence of toxicity in the F0 females given either MAA or vaccine. There were no effects on the fertility or reproductive performance of the F0 females. There was no evidence of developmental toxicity to the F1 generation, including fetal body weight and morphology, postnatal growth and development, behavior, and reproductive performance. The quadrivalent vaccine induced a specific antibody response to the four HPV types in the F0 female rats following one or multiple injections. Antibodies against all four HPV types were transferred to the F1 generation during gestation and/or lactation, likely via the placenta and milk, respectively. The passively transferred antibodies persisted up to Postnatal Day 77 when they were last measured. These results demonstrate that this quadrivalent HPV vaccine had no detectable adverse effects in either the treated F0 female rats or the F1 generation. Birth Defects Res (Part B) 83:561–572, 2008. © 2008 Wiley‐Liss, Inc.     

Reproductive toxicity assessment of lasofoxifene, a selective estrogen receptor modulator (SERM), in male rats

BACKGROUND: Lasofoxifene is a nonsteroidal selective estrogen receptor modulator (SERM) with greater than 100-fold selectivity against all other steroid receptors and is a potentially superior treatment for postmenopausal osteoporosis. The purpose of this study was to evaluate the effects of lasofoxifene on male reproduction in rats in light of the known effects of estrogen modulating compounds on male reproductive ability. METHODS: Lasofoxifene was administered to adult male rats at doses of 0.1, 1, 10, and 100 mg/kg for 66-70 consecutive days. After 28 days of dosing, male rats were cohabited with untreated female rats. Female rats were euthanized on gestation day 14 and a uterine examination was carried out for evaluation of reproductive parameters and embryo viability. Male rats were euthanized after 66-70 days of dosing and epididymal sperm motility and concentration were assayed. The testes, epididymides, prostate, and seminal vesicles were weighed and microscopically examined. RESULTS: The duration of cohabitation was increased for 100 mg/kg males by 0.7 days. The number of males copulating and the number of implantation sites produced per copulation were reduced in the 10 and 100 mg/kg groups. Weights of the seminal vesicles and epididymides were reduced for all groups, although the testes weight and epididymal sperm motility and concentration were not affected by treatment. There were no microscopic findings in the male reproductive tissues. CONCLUSION: The changes in male fertility and reproductive tissue weights after exposure to lasofoxifene are consistent with those previously described for estrogen receptor-modulating compounds.     

Assessment of female and male fertility in Sprague-Dawley rats administered vorinostat, a histone deacetylase inhibitor

BACKGROUND: Histone deacetylase (HDAC) inhibitors have been shown to mediate the regulation of gene expression, induce cell growth, cell differentiation, and apoptosis of tumor cells. These compounds are now marketed or are in clinical development. One such HDAC inhibitor, vorinostat (suberoylanilide hydroxamic acid [SAHA], Zolinza), was assessed for its potential effects on fertility in Sprague–Dawley rats. METHODS: Female rats were administered oral dose levels of 0 (vehicle only), 15, 50, or 150 mg/kg/day of vorinostat for 14 days before cohabitation, during cohabitation, and through Gestation Day (GD) 7. In a separate study, male rats were administered oral dose levels of 0 (vehicle only), 20, 50, or 150 mg/kg/day for 10 weeks before cohabitation, during cohabitation, and until the day before scheduled sacrifice (approximately 14 weeks total). In both studies, % peri‐implantation loss and % postimplantation loss were evaluated on GD 15–17. Testicular weight and histomorphology, cauda epididymal sperm count, and sperm motility were evaluated in the male rat study at termination. RESULTS: There were treatment‐related decreases in body weight gain at 150 mg/kg/day in both studies. There were no effects on mating or fertility indices in either study. In the female study there were increased numbers of corpora lutea in all drug‐treated groups (only 1 or 2 affected dams in low and mid‐dose groups), and a marked increase in percent postimplantation loss only in the high‐dose group. No treatment‐related effects were observed on litter or sperm parameters of the male study. CONCLUSIONS: Vorinostat had no effects on mating or fertility in rats up to 150 mg/kg/day. There were no indications of reproductive toxicity in drug‐treated male rats. Increases in corpora lutea or resorptions were observed in treated female rats. Birth Defects Res (Part B) 80:1–8, 2007. © 2007 Wiley‐Liss, Inc.     

Effect of Filgrastim on adult male rats’ fertility and reproductive performance

Filgrastim is a recombinant protein used in treatment neutropenia caused by myelosuppressive medications for patients with non-myeloid cancer. However, its effect in male fertility is not clear. So, the current work aims to clarify the effect of Filgrastim on the reproductive state in Wistar rats. Eighteen (18) male Wistar rats were divided into three groups (6/each). Group (I) where the rats were injected with 0.5 ml/kg/day of distilled water and served as Control Group. The Group (II) animals received intraperitoneal injection of therapeutic dose of 30.83 mcg/kg/day of Filgrastim for one week. The Group (III) rats received the same dose by the same route of Filgrastim for two weeks. Sera of blood samples were processed for serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (TS). Semen analysis and resazurine reduction test (RRT) were performed. Assaying for malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) was done. The testes were retrieved for histopathological and immunohistochemical studies for caspase-3 detection. Our results revealed that filgrastim affects sperm morphology, significantly decreased the RRT and the reproductive hormones level, elevated the oxidative stress status and induced several histopathological changes in testes with an increased in immunoexpression of caspase-3 in testes tissues. The results of this work demonstrated that Filgrastim may had a deleterious effect on male fertility.     

Diethylstilbestrol-treated adult rats with altered epididymal sperm numbers and sperm motility parameters, but without alterations in sperm production and sperm morphology

In this study, we characterized estrogenic effects of diethylstilbestrol (DES) on reproductive parameters in male rats to identify a minimal dose level that alters epididymal and sperm functions but has little or no effect on sperm production and/or spermatogenesis. Adult rats (five animals/group) received s.c. injections of 0.2 ml of corn oil containing DES at a rate of 1.0 mg, 200 microg, 40 microg, 8 microg, 1.6 microg, or 320 ng x rat(-1) x day(-1) for 12 days. The control group received corn oil only. DES effects were similar in the 8-microg group and higher dose groups and included significant (P < or = 0.05) reductions in 1) absolute and relative weights of the head and body of the epididymis (EP), tail of the EP, and seminal vesicle, 2) numbers of sperm in both regions of the EP, and 3) motility characteristics in sperm collected from the tail of the EP. Conversely, no significant changes were observed in relative testis weight, daily sperm production, spermatogenesis, seminiferous epithelial height in stage VII, and sperm morphology. All of the above parameters in the 1.6-microg group (except seminal vesicle weight) and 320-ng group were comparable to those of controls. Plasma testosterone (T) level was reduced to an almost undetectable level in the > or = 8-microg groups and to a very low level in the 1.6-microg group (0.35 vs. 2.36 ng/ml in controls or 320-ng group), but LH level was unaltered. In a parallel fertility study, males received DES at a rate of 40, 8, or 1.6 microg x rat(-1) x day(-1) for 12 days prior to and 12 days during cohabitation (1:1) with untreated females. Of the 15 females cohabited with treated males (5 females/dose), none in the 40-microg and 8-microg groups and 1 in the 1.6-microg group formed a copulatory plug and delivered 8 pups, in contrast to 5/5 copulatory plugs and 13-15 pups/litter in the controls. DES at a rate of 8 microg x rat(-1) x day(-1) for 12 days reduced EP weights, sperm numbers in the EP, and sperm motility patterns but caused minimal to no alterations in daily sperm production, spermatogenesis, or sperm morphology. Factors other than T, or in addition to lower T, may be responsible for DES-induced reproductive disorders (despite lower T, sperm contents and sperm motility patterns in the EP were normal in the 1.6-microg group). Deficits in EP sperm functions and/or sexual behavior (as evident from absence of copulatory plugs) probably accounted for reduced fertility in treated males.     

Effects of seminal vesicle removal on fertility and uterine sperm motility in the house mouse

The relative significance of the accessory glands of the male reproductive tract in fertility is unclear. To clarify the role of the seminal vesicles, fertility and uterine sperm motility were determined before and after removal of seminal vesicles in the house mouse. After removal of seminal vesicles, the pregnancy rate (number of females pregnant/number of females X 100) was reduced and the time to birth was increased, while the average litter size was not changed. Fertilization, determined by examining the oocytes 30 h after mating, was highly variable after matings with males whose seminal vesicles were removed; in some cases none of the oocytes were fertilized. The motility of sperm recovered from the uterus 1 h after matings with males before and after seminal vesicle removal and sham operations was analyzed using a videomicrographic system. The motility of uterine sperm was less progressive with more lateral displacement of the head about the trajectory and a less linear trajectory after removal of the seminal vesicles. Sham-operated animals showed no consistent changes in motility of uterine sperm. The changes in sperm motility could contribute to the reduction in fertilization since sperm motility is necessary for transport in the female reproductive tract and interaction with the oocytes.     

Impact of experimental diabetes and insulin replacement on epididymal secretory products and sperm maturation in albino rats

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. J. Cell. Biochem. 108: 1094–1101, 2009. © 2009 Wiley‐Liss, Inc.     

Male reproductive maturity and diapause termination in the leaf beetle Gastrophysa atrocyanea

Male reproductive potential and growth of testes are studied in the leaf beetle Gastrophysa atrocyanea Motschulsky (Coleoptera: Chrysomelidae) that is exposed to mild temperatures after imaginal ecdysis. Continuous administration of the Juvenile Hormone (JH) in artificial diet is highly effective with respect to stimulating testes growth and mating behaviour. Female reproductive diapause can be induced under standard rearing conditions, although optimum reproductive maturity of males is achieved at 15 °C. Treatment of males with a JH analogue accelerates testes development up to the stage of spermiogenesis (the bundling of spermatozoa) but does not promote the formation of cysts with mature sperm. Treatment with 20‐hydroxyecdysone has no influence on diapause termination and testes function. These results suggest that male reproductive maturation in G. atrocyanea is independent of JH, and moderate temperatures may induce an unknown factor that is responsible for the maturation of sperm cysts.     

Ameliorating effects of agomelatine on testicular and epididymal damage induced by methotrexate in rats

The aim of this study was to investigate the possible prophylactic effects of agomelatine (AGO) against testicular and epididymal damage induced by methotrexate (MTX) in rats. Twenty‐four male Wistar albino rats were divided into three groups: Group I (control group), Group II (MTX group: 20 mg/kg MTX, i.p, single dose), and Group III (MTX+AGO group: 20 mg/kg MTX, i.p, single dose+40 mg/kg AGO; gavage, 7 days). The rats were killed under anesthesia 24 hours after the last AGO application. Testicular and epididymal tissues were bilaterally removed for morphometric, biochemical, pathological, and immunohistochemical analyses. Body, testicular, and epididymal weights were measured. Malondialdehyde (MDA), superoxide dismutase, catalase, and glutathione peroxidase levels were measured in testes. Sperm count, hyperemia, edema, inflammatory reaction, degenerated and necrotic cells were evaluated by histopathological analysis. In addition, inducible nitric oxide synthase (iNOS), granulocyte colony‐stimulating factor (G‐CSF), osteopontin (OPN), and heat shock protein‐70 (HSP70) immune reactions were analyzed in testes and epididymides. Decreased epididymal weights, increased MDA levels, decreased sperm count, hyperemia, edema, inflammatory reaction, and degenerated and necrotic cells were observed in the MTX group. In addition, iNOS, HSP70, G‐CSF, and OPN immune reactions were increased. AGO improved morphometric, biochemical, histopathological, and immunohistochemical findings. The present study confirms that MTX induces testicular and epididymal damage both biochemically and immunohistochemically. However, AGO demonstrated ameliorative effects on both biochemical and pathological findings of the current study.     

Clock-controlled rhythm of ecdysteroid levels in the haemolymph and testes, and its relation to sperm release in the Egyptian cotton leafworm, Spodoptera littoralis

In Spodoptera littoralis, testicular sperm release occurs in a daily rhythm, which is controlled by endogenous circadian oscillator located in the male reproductive system. Although this rhythm is essential for male fertility, factors that initiate and maintain daily sperm release are not understood. In this study, we investigated a modulatory role for ecdysteroids in the sperm release rhythm and identified the source of ecdysteroids in adult males. We found that the onset of sperm release occurs two days pre-eclosion and coincides with a significant decrease in haemolymph ecdysteroids levels. 20-HE injection into the pupae prior to the first sperm release delayed its initiation and disrupted the developing rhythm in a dose dependent manner. 20-HE injection into adults depressed the number of sperm bundles leaving the testes. A day before the initial sperm release, ecdysteroid levels in the haemolymph and testes begin to oscillate in a circadian fashion. Ecdysteroid rhythms continue throughout imaginal life and correlate with the rhythm of sperm release. In each cycle, testicular sperm release coincides with a trough in testicular ecdysteroid concentration. Rhythmic changes in ecdysteroid levels are regulated by an endogenous circadian oscillator that continues to function in decapitated males. The generation of a complete cycle of ecdysteroid release by testes cultured in vitro indicates that this oscillator is located in the gonads. The haemolymph ecdysteroid levels are significantly lower and arrhythmic in males with removed testes, indicating that the testes are an important ecdysteroid source that may contribute to oscillations in haemolymph ecdysteroid levels.     

α‐Lipoic acid inhibits testicular and epididymal oxidative damage and improves fertility efficacy in arsenic‐intoxicated rats

The present study evaluates the protective effect of α‐lipoic acid (LA) against arsenic‐induced testicular and epididymal oxidative damage in rats. Arsenic caused significant reduction in the reproductive organ weights, serum testosterone levels, testicular daily sperm count, epididymal sperm count, sperm motility, sperm viability, and sperm membrane integrity. Significant reduction in the activity levels of superoxide dismutase, catalase, and glutathione levels with a concomitant increase in the lipid peroxidation and protein carbonyl content in the testis and the cauda epididymis of arsenic‐exposed rats. Arsenic intoxication also enhanced the testicular caspase‐3 mRNA levels, disorganization of testicular and cauda epididymal architecture as well as increased arsenic content in the testis and the cauda epididymis of rats. Arsenic exposure also deteriorated fertility ability in male rats over controls. Conversely, α‐LA negated the testicular and cauda epididymal oxidative stress and restored the male reproductive health in arsenic‐exposed rats.     

Effect of apoptosis‐associated speck‐like protein containing a caspase recruitment domain on vaccine efficacy: Overcoming the effects of its deficiency with aluminum hydroxide adjuvant

Host factors such as nutritional status and immune cell state are important for vaccine efficacy. Inflammasome activation may be important for triggering vaccine‐induced humoral and cell‐mediated immune responses. Formulations with alum as a typical adjuvant to overcome the effects of host factors have recently been shown to induce inflammasome activation, which augments vaccine efficacy. Apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC) is one of the main components of inflammasomes, but it is not clear whether ASC affects the vaccine‐induced immune response. Herein, we used two types of vaccines: inactivated influenza vaccine not formulated with alum, and HPV vaccine formulated with alum. We gave the vaccines to ASC knockout (ASC^?/?) mice to investigate the role of ASC in vaccine efficacy. Influenza vaccine‐immunized ASC^?/? mice did not show antibody titers in week 2 after the first vaccination. After boosting, the antibody titer in ASC^?/? mice was about half that in wild type (WT) mice. Furthermore, a cytotoxic T‐lymphocyte response against influenza vaccine was not induced in ASC^?/? mice. Therefore, vaccinated ASC^?/? mice did not show effective protection against viral challenge. ASC^?/? mice immunized with alum‐formulated HPV vaccine showed similar antibody titers and T‐cell proliferation compared with immunized WT mice. However, the HPV vaccine without alum induced up to threefold lower titers of HPV‐specific antibody titers in ASC^?/? mice compared with those in WT mice. These findings suggest that alum in vaccine can overcome the ASC‐deficient condition.

     

ZNF185‐derived peptide induces fertility suppression in mice

Zinc finger protein 185 (ZNF185) belongs to the ZNF family and is involved in male reproduction. However, it is unclear whether ZNF185 may be a target candidate for contraceptive vaccines. In this study, antigenic peptides derived from ZNF185 were prepared, and their immune contraceptive effects were investigated using mice. Results from enzyme‐linked immunosorbent assay (ELISAs) showed that peptide immunization induced an antibody titre increase that reached a peak in week 12. Peptide‐3 and peptide‐4 were then chosen for subsequent experiments. The results of the fertility assays showed that peptide immunization inhibited the mating and fertility rates of the mice, whereas there were no obvious changes in the number of pups per litter. Subsequently, epididymal sperm was analysed. The results demonstrated that the sperm count and sperm motility were significantly decreased in the peptide group, while the amount of abnormal sperm was significantly increased in the peptide‐3 group. The male reproductive organs were also evaluated. There were no obvious differences in testis or epididymal weights, in the diameters of the seminiferous tubules, or in the thicknesses of the seminiferous epithelium between the peptide group and the phosphate buffer saline (PBS) group. In addition, histological analysis indicated that there were no obvious pathologic changes in testis and epididymal histology in the peptide group; however, the number of spermatozoa present in the epididymal lumen of the peptide group was significantly decreased when compared with the PBS group. Our study demonstrates for the first time that peptides derived from ZNF185 may induce fertility suppression in mice without damaging reproductive organs. These peptides have the potential to be used as a male contraceptive vaccine.     

Mutation of cyp19a1b results in sterile males due to efferent duct obstruction in Nile tilapia

The involvement of estrogen in male fertility has been well established in mammals. However, less is known about the role of estrogen in fish male reproduction. Our recent study revealed that Cyp19a1a deficiency had no effect on fertility in male fish. In this study, expression of Cyp19a1b, but not Cyp19a1a, was detected by immunohistochemistry in Leydig cells of tilapia testes. cyp19a1b mutation resulted in a significant decrease in the concentration of 17β‐estradiol in serum and sterility in XY fish, as no offspring were obtained when crossed with control XX fish at 240 days after hatching (dah). No sperm was obtained from the mature mutants by in vitro extrusion. Further examination of the mutant gonads revealed excessive semen accumulation and testicular hypertrophy. Semen collected from the mutant testes during autopsy contained sperm with a normal morphology that showed no significant differences in motility, VCL, BCF, STR, or fertility compared with control sperm. Efferent ducts from the mutant testes, which had low‐convolution levels, fewer branches, and no blood vessels observed inside the walls, were significantly smaller in size. qRT‐PCR analyses showed downregulated expression of ion exchange genes. There was increased apoptosis in the epithelial cells of the efferent ducts and other somatic cells of the testes as revealed by TUNEL staining, as well as upregulation of apoptosis gene expression in the mutants. At 360 dah, mutant fish showed testicular atrophy and efferent duct fibrosis. These results demonstrated that estrogen deficiency caused by Cyp19a1b mutation resulted in male sterility due to efferent duct obstruction.     

Effect of overdose zinc on mouse testis and its relation with sperm count and motility

The purpose of this study was to investigate the effects of excessive zinc intake on the testes and on sperm count and motility in mice. Thirty Balb c mice were divided randomly into 3 groups of 10 animals in each. Group I acted as controls; group II was supplied with drinking water containing 1.5 g/100 mL Zn, and group III was supplied with drinking water containing 2.5 g/100 mL Zn. The animals were sacrificed after 3 wk supplementation and the epididymis and testis were quickly excised. A negative correlation between Zn dose and sperm count and motility was found. The sperm count in group III was significantly lower than in groups II and I (p<0.05). The sperm motility in group III was significantly lower than in the controls (p<0.05). Degenerative changes, including spermatic arrest, degeneration of seminiferous tubules, and fibrosis in interstitial tissue, were observed in group III animals. These results show that high doses of zinc significantly alter sperm motility.     

度他雄胺对大鼠附睾精子成熟和生育的影响

目的通过度他雄胺对大鼠附睾精子和生育的影响,探索调节雄性生育的睾丸后作用靶点。方法使用度他雄胺20和40 mg/(kg.d)大鼠灌胃给药,连续2周。给药结束后雄雌鼠按1∶2合笼,计算生殖指数;采用计算机辅助精子分析系统分析精子活力和形态;采用SYBR-14和PI双重荧光染色计算精子存活率;采用Elisa法测定大鼠睾酮(T)和双氢睾酮(DHT)血清浓度;采用HE染色法对各组睾丸、附睾进行组织学分析。结果度他雄胺低、高剂量组双氢睾酮浓度均显著下降,分别为0.54和0.28 nmol/L(P<0.01),精子活力明显降低,分别为39.0%和28.7%(P<0.01),畸形率分别增加为10.3%和15.6%(P<0.05),最后受孕率分别降为62.5%和38.4%。而睾酮水平和交配指数均无明显变化(P>0.05),睾丸和附睾亦无明显病理学改变。结论度他雄胺通过抑制DHT生成,影响附睾精子成熟而导致大鼠不育,为今后男性避孕和不育药物研发提供了新思路。     

Effect of aging on male reproduction in zebrafish (Danio rerio)

The study was designed to test the hypothesis that male aging is associated with a change in reproductive function in the zebrafish. Young (290 ± 37 d) and older (911 ± 48 d) males were combined with females (604 ± 24 d) to test the effect of male age on the number and fertility of eggs laid by their mates. 48% of breeding trials with young males and 25% of the trails with older males resulted in egg deposition. Although young males were associated with significantly more successful breeding attempts than older males, number of eggs laid per clutch, number and percent of fertilized eggs and the number and percent living embryos were not statistically different between young and older males. These data suggest that male aging is associated with altered reproductive behavior and/or female response but not in sperm quality per se. Consistent with this interpretation were the findings that percent motility and sperm motility characteristics did not differ between sperm from young and older males as assessed by computer-assisted sperm analysis. However, older males contained higher quantities of extractable sperm than did young males, perhaps associated with fewer successful breeding attempts. Age-related effects on male reproductive in the zebrafish may therefore be a consequence of behavioral or morphological features that play a role in female mate choice and/ or male sexual response.     

Effectiveness of bivalent and quadrivalent human papillomavirus vaccination in Luxembourg

BackgroundIn Luxembourg, the human papillomavirus (HPV) vaccination program introduced in 2008, provided either bivalent (BV) or quadrivalent (QV) vaccines to girls aged 12–17 years. Here, we estimate the effectiveness of BV and QV vaccines combined and separately in reducing type-specific HPV prevalence eight years after the introduction of the vaccination program.MethodsA cross-sectional prevalence study was conducted among women aged 18–29 years in 2015-2017. Seven hundred sixteen participants were recruited at family planning centres or private gynaecology practices in Luxembourg. Vaccination records were verified in the social security database. Cervical samples were tested using the Anyplex II HPV28 assay. Vaccine effectiveness was estimated using logistic regression.ResultsIn total, 363/716 (50.7%) participants were HPV positive with any HPV and 209/716 (29.2%) with carcinogenic HPV genotypes. HPV vaccination offered high protection against HPV16/18 (adjusted odds ratio (AOR) = 0.13; 95% CI 0.03-0.63), HPV6/11 (AOR = 0.16; 95% CI 0.05-0.48) and cross-protection against HPV31/33/45 (AOR = 0.41; 95% CI 0.18-0.94). The AORs were generally enhanced when only considering vaccination before sexual debut corresponding to AORs: 0.05 (95% CI 0.00-0.88), 0.08 (95% CI 0.02-0.36) and 0.20 (0.06-0.65) against HPV16/18, HPV6/11 and HPV31/33/45, respectively. We observed significant protection against carcinogenic genotypes included in nonavalent vaccine for BV (AOR = 0.29; 95% CI 0.13-0.67), but not for QV (AOR = 0.81; 95% CI 0.47–1.40) (heterogeneity Chi² P = 0.04).ConclusionsOur study suggests high effectiveness of HPV vaccination against HPV6/11, HPV16/18 and a cross-protection against HPV31/33/45. Vaccination effectiveness was slightly higher for women vaccinated before sexual debut.     

Prevention of chronic alcohol and nicotine-induced azospermia,sterility and decreased libido,by a novel tri-substituted benzoflavone moiety from Passiflora incarnata Linneaus in healthy male rats

Excessive long term consumption of alcohol and nicotine have serious detrimental effects upon the libido, fertility, and sperm count in male species. The present work describes the beneficial effects of a novel tri-substituted benzoflavone moiety (BZF) isolated from Passiflora incarnata Linneaus, the phyto-chemical isolation, spectroscopic elucidation, and multifarious biological activities of which have recently been reported by the authors. The BZF moiety has been reported to increase libido, sperm count, and sexual fertility in 2 years old male rats at 10 mg/kg, po dose, in the one of our previous studies. Presently, the BZF moiety has been evaluated against chronic ethanol- and nicotine-induced decrease in libido, sexual fertility and mating efficiency in healthy male rats. The male rats were given ethanol (3 g/kg, po) A, nicotine (2 mg/kg, sc) N, alcohol-nicotine combinations (AN) alone, and also with 10 mg/kg po dose of BZF (concurrent administrations). These treatments were given for 30 days. At the end of treatments, it was observed that rat groups A, N, and AN had no libido (evaluated by mounting behaviour), declined sperm count, and consequently no mating efficiency or fertility (upon pairing with pro-estrus female rats). However, the rats which were given 10 mg/kg BZF along-with nicotine (NP group), alcohol (AP group), and alcohol-nicotine combination (ANP) exhibited significant libido-oriented mounting behaviour, increased sperm count (significantly comparable to the control group), and increased fertilization potential. The rats having decreased sperm count, libido and fertilization potential due to chronic administration of alcohol, nicotine and alcohol-nicotine combinations, i.e., rats of A, N, and AN groups were again subdivided and were given 10 mg/kg BZF for 7 days. This treatment confirmed that BZF speeds up the restoration of sexuality in rats upon cessation of the administration of substances like alcohol, nicotine and alcohol-nicotine combinations, which have severe detrimental effects upon male sexuality, fertility and vigour. BZF, the strongest inhibitor of aromatase enzyme, when administered concurrently with substances like alcohol and nicotine restores sexual virility, libido and vigour in male rats by maintaining the blood-testosterone levels to be high.     

Effects of plumieride, an iridoid on spermatogenesis in male albino rats.

Oral feeding of male rats with plumieride (15 mg/rat/day) for the period of 60 days did not cause any significant change in the body weight of treated rats. However, the weights of testes, epididymides, seminal vesicle and ventral prostate were significantly reduced when compared to control values. The production of step-19 spermatids was reduced by 87.26% in plumieride treated rats. The population of preleptotene and pachytene spermatocytes were decreased by 64.26% and 55.13% respectively. Spermatogonia and sertoli cell population was also affected. Plumieride treatment resulted in an arrest of spermatogenesis without any systemic side effect. Sperm motility as well as sperm density was reduced significantly. The number of mature Leydig cells was decreased and complete suppression of fertility was observed. A significant fall in the protein and sialic acid contents of the testes, epididymides, seminal vesicle and ventral prostate as well as glycogen content of testes was also noticed. Fructose in seminal vesicle was lowered whereas testicular cholesterol was elevated. There was no significant change in RBC and WBC count, haemoglobin, haematocrit and sugar in the whole blood and total protein, cholesterol, phospholipid and triglycerides in the serum. Conclusion: Plumieride administration arrests spermatogenesis in male rats without noticeable side effects. For the clinical use more experiments should be carried out in a phased programme.