F.W. Bansode

Erratum to “Next Generation Sequencing: Potential and Application in Drug Discovery”

Through this erratum the authors declare that two coauthors were missing in the article entitled “Next generation sequencing: potential and application in drug discovery”. The correct list of the authors and their affiliations are as shown above.

Uterine luminal epithelial alkaline phosphatase activity and pinopod development in relation to endometrial sensitivity in the rat

The period of maximal endometrial sensitivity in the rat was characterized by high alkaline phosphatase activity in uterine luminal and glandular epithelium and endometrial stroma. The activity in endometrial stroma increased following decidualization. Pinopod development on the endometrial surface was first observed during the presensitivity period. Their number increased, apparently more so on the antimesometrial rather than the mesometrial segment of the uterus, on the day of maximal sensitivity. Inhibition in endometrial sensitivity by single anti-implantation (1.25 mg/kg, po) dose of centchroman on day 1 post-coitum (p.c.), although it did not affect alkaline phosphatase activity on days 2 and 3 p.c., caused complete inhibition in its activity in uterine luminal and glandular epithelium and pinopod development on days 4 and 5-coinciding, respectively, with time of entry of preimplantation embryos into the uterus and period of maximal endometrial sensitivity in this species. Significant decrease in enzyme activity was also evident in the entire endometrial stroma and myometrium, except blood capillaries, on these days. In comparison, prevention of entry of native embryos into the uterus by placing a ligature at the utero-tubal junction had no effect on pinopod development, but caused marked decrease in enzyme activity in luminal and glandular epithelium only during the immediate postimplantation period. The uterine lumen on the day of maximal sensitivity in centchroman-treated rats appeared highly distended and was lined with tall columnar epithelium, in comparison to low cuboidal epithelium in controls. The findings demonstrate: (a) a correlation between uterine luminal epithelial alkaline phosphatase activity and endometrial sensitivity; (b) complete inhibition in enzyme activity in luminal and glandular epithelium following centchroman treatment might be related to altered permeability characteristics of epithelial cells, which together with the absence of pinopods and highly distended uterine lumen on the day of maximal sensitivity, suggest inhibition of endocytosis/pinocytosis of luminal fluid, luminal closure, apposition of blastocyst trophoblast to luminal epithelium, and secretory activity of glandular epithelium; (c) pinopod development on the endometrial surface was independent of presence of viable blastocysts in utero; and (d) complete absence of pinopods suggests lack of endometrial sensitivity, but their presence might not necessarily indicate a sensitized endometrium in the rat.

Inhibition of hyaluronidase activity of human and rat spermatozoa in vitro and antispermatogenic activity in rats in vivo by Terminalia chebula, a flavonoid rich plant ☆

Our interest in development of hyaluronidase inhibitors as male antifertility agents led to identification of Terminalia chebula (T. chebula) plant with hyaluronidase (HAase) inhibitory activity of human spermatozoa ( approximately 93% inhibition) and rat caudal epididymal spermatozoa ( approximately 86% inhibition) in vitro at 30 mg/ml. We further demonstrated inhibition of hyaluronidase activity of testis and epididymal spermatozoa in vivo coincident with antispermatogenic activity and contraceptive efficacy of TC extract administered at 50 and 100mg/kg/day orally for 60 days in male albino rats. The significant decrease in motility, count and increase in morphological abnormalities of epididymal spermatozoa and severe reduction in fertility (-100%) of male rats treated with T. chebula fruit extract at 100mg/kg dose could be attributed to either direct effect on testis or direct or indirect interference with sperm maturation in epididymis, and/or inhibition of testicular and epididymal sperm hyaluronidase enzyme in vivo probably caused by flavonoids like tannins present in T. chebula.

Seasonal changes in the seminiferous epithelium of rhesus and bonnet monkeys.

Abstract: With a view to elucidate seasonal variations in testicular spermatogenesis, quantitative analysis of spermatogenic cells was carried out in non‐human primate species viz. rhesus (Macaca mulatta) and bonnet (M. radiata) monkeys during breeding (October–December) and non‐breeding (May–June) seasons. The results revealed significant inhibition of testicular germ cell population during non‐breeding compared with the breeding period in both the species. Quantitative determination of Sertoli cell–germ cell ratio showed a marked decrease in the number of type A‐spermatogonia, spermatocytes (non‐pachytene and pachytene) and spermatids (in steps 1–12 of spermiogenesis) in rhesus monkey during the non‐breeding period. Bonnet monkeys exhibited the significant decline in the number of primary spermatocytes and spermatids during the non‐breeding phase. In addition, average diameter of round seminiferous tubules and nuclear diameter of Leydig cells also decreased significantly in rhesus monkeys. However, bonnet monkeys did not show any significant change in nuclear diameter/morphology of Leydig cells, testicular tubular diameter and number of type A‐spermatogoniae. Sertoli cell number did not show any significant change during both breeding and non‐breeding periods in both the species. The results of this study indicate a prominent seasonal variation in testicular spermatogenic/Leydig cells in rhesus monkeys than those observed in bonnet monkeys.

Quantitative analysis of spermatogenesis in rats made azoospermic with compound CDRI 84/35

Abstract Compound CDRI 84/35 (1-formyl-4-dichloroacetamidopiperazine) was reported to exert its effect on seminiferous epithelium without affecting Leydig cells and accessory sex organs. Adult rats administered CDRI 84/35 (100 mg/kg body weight for 15 days followed by 25 mg/kg) showed a significant atrophy of testis indicating 21.8 ± 4.4, 79.6 ± 5.3, 94.8 ± 2.1 and 79.5 ± 2.1% abnormal tubules at 22, 41, 54, and 64 days following treatment at the time of autopsy). The Sertoli cell-germ cell ratio showed a significant reduction in number of primary spermatocytes and spermatids during the treatment. Marked decrease in pachytene spermatocytes and in stages of spermatogenesis was observed on day 54. In contrast, the testes in estradiol benzoate (EB; 5 g/rat/day) treated rats showed 64.6% ± 21.85% abnormal tubules at day 22 and almost all affected tubules on from day 41 onwards, exhibiting a significant decline in number of spermatocytes and spermatids, while spermatogonia were affected only at 64 days of treatment. Reversibility studies showed 76.5% ± 2.1% normal tubules with significant inhibition in spermatogenesis following 60 days cessation of CDRI 84/35. At 120 days recovery, 74.7% ± 18.8% testicular tubules revealed quantitatively normal spermatogenesis, whereas 25.3% ± 18.8% tubules showed incomplete recovery of spermatogenesis until 120 days. The present study revealed a marked inhibition of spermatogenesis at the pachytene spermatocyte stage by CDRI 84/35 compared to EB in the seminiferous epithelium of rat. Its antispermatogenic effect was found to be irreversible up to 120 days.

Development of a Nanotechnology Based Biomedicine RISUG-M as a Female Contraceptive in India

Background and objectives: The aim of this study was to assess the toxic effect of the newly developed contraceptive RISUG-M in female Charles Foster rats. Methods: Young, healthy and nulliporus female rats of Charles Foster strain were employed in the study. They were randomly assigned to two groups, control and treated each consisting of female animals. The contraceptive RISUG-M was injected in the fallopian tube of the treated group rats while only vehicle was injected in control group rats’ fallopian tube and observed for a period of 14 days. Initial and final body weights and food/water consumption of the animals were recorded. The haematological and biochemical parameters were analyzed. At the end of the study all the animals were sacrificed and necropsied, the organ weight was taken and their histopathological slides were prepared for microscopic examination. Results: Body weight, food and water consumption, haematology, biochemistry, absolute and relative organ weights did not show any significant change and were well within the limit of normalcy. General health check-up, mortality, gross and microscopic examination of organs and tissues also did not reveal any sign of toxicity. Interpretation and conclusions: From the toxicity point of view this newly developed injectable contraceptive RISUG-M does not have any adverse effect and is safe to use.

Dose-dependent effects of Asparagus adscendens root (AARR) extract on the anabolic, reproductive, and sexual behavioral activity in rats.

Abstract Context: Asparagus adscendens Roxb (Liliaceae) has a promising role in modulation of various disorders such as leucorrhea, diarrhea, dysentery, diabetes, senile pruritus, asthma, fatigue antifilarial, antifungal, spermatorrhea, and sexual debility/seminal weakness. Objective: To investigate dose-dependent effects of Asparagus adscendens root (AARR) extract on anabolic, reproductive, and sexual behavioral activities with a view to emphasize the pharmacological basis. Materials and methods: Rats were divided into five groups: Group I (control), Groups II–IV (AARR treated, 100, 200, and 300 mg/kg body weight, respectively, orally for 30 d) and Group V (standard control treated with sildenafil citrate, 5 mg/kg body weight). On day 31, copulatory and potency tests were carried out and an autopsy was done to study the reproductive function, namely, organ weights, spermatogenesis, daily sperm production rate (DSP), and epididymal sperm counts (ESC). Results: AARR extract (200 and 300 mg/kg doses) caused a significant increase in body (p < 0.02 and p < 0.001) and testes (p < 0.01 and p < 0.001, control versus treated) weights. Reproductive activity showed significant a increase in testicular tubular diameter (p < 0.005–0.001), the number of round/elongated spermatids (p < 0.02–0.001), DSP, and ESC (p < 0.05–0.001). The sexual behavioral parameters including mounting/intromission frequency (13.0 ± 0.32/11.8 ± 0.37 and 18.2 ± 2.12/14.8 ± 1.15 versus 11.2 ± 0.66/8.2 ± 1.16), ejaculation latency (187.4 ± 1.91 and 191.4 ± 1.72 versus 180.0 ± 3.47), and penile erections (13.5 ± 0.3 and 14.5 ± 0.5 versus 8.5 ± 0.2) showed a significant increase at 200 and 300 mg/kg doses (ED50 300 mg/kg), but less than a standard control. In contrast, 100 mg/kg dose caused an increase (p < 0.005) in mounting latency only. Conclusion: These results indicate increased anabolic, reproductive, and sexual activities by AARR treatment. Thus, the data provide scientific rationale for its traditional use as an aphrodisiac or for sexual disorders.

Dose-dependent effects of ethanol extract of Salvia haematodes Wall roots on reproductive function and copulatory behaviour in male rats

This study was aimed to investigate the dose‐dependent effects of Salvia haematodes Wall roots (SHW) extract on male reproductive function and copulatory behaviour in rats. Sexually mature males were assigned to four groups: control and treated (5, 50 and 300 mg kg−1 day−1 for 30 days). At the end of treatment regimes, the reproductive activity viz. body/organ weights, testicular spermatogenesis, daily sperm production rate (DSP) and epididymal sperm counts, and sexual behaviour including mounting latency (ML), mounting frequency (MF), intromission latency (IL), intromission frequency (IF), ejaculation latency (EL), post‐ejaculatory interval (PEI) and penile reflexes (PE) were assessed. Results showed significant increase in body weight (at 300 mg kg−1), testis/epididymis weights (at 50 and 300 mg kg−1), testicular spermatids, DSP, tubular diameter and epididymal sperm counts (at 50 and 300 mg kg−1doses) in treated compared with control rats. It also produced dose‐dependant changes in sexual behaviour. The 5 mg kg−1 dose of extract increased MF and PE, whereas 50 and 300 kg−1 doses caused significant increase in MF, IF, PE, EL (but less than sildenafil citrate treatment), hit rate and seminal plug weight. It is concluded that SHW extract enhances anabolic activity, testicular function and sexual behavioural performance in a dose‐dependant manner.