Exposure of male Albino Swiss rats to the nonsteroidal antiandrogen flutamide during the period from gestational day (d) 10 to birth resulted in feminisation of the external genitalia and the suppression of growth of the male reproductive tract. In adulthood, testes were found to be located in diverse positions. True cryptorchidism occurred in 10 % of cases, whereas 50 % of testes descended to the scrotum and 40 % were located in a suprainguinal ectopic region. Varying degrees of tubule abnormality were seen in the testes of flutamide-treated animals, ranging from completely normal tubules with full spermatogenesis (and the expected frequency of the stages of spermatogenesis) to severely abnormal tubules lined with Sertoli cells only. For each individual testis, the overall severity of tubule damage was strongly correlated with its adult location, with intra-abdominal testes worst affected and scrotally-located testes least ; only the latter contained normal tubules. Similarly, intra-abdominal testes were the smallest in weight and contained the least testosterone. By contrast, postnatal treatment of male rats with flutamide from birth to postnatal d 14 did not impair development of the external genitalia, the process of testicular descent or adult spermatogenesis. These findings confirm that androgen blockade during embryonic development interferes with testicular descent but also demonstrate that (1) prenatal flutamide treatment per se has a detrimental effect on adult testis morphology but (2) the degree of abnormality of the testes is strongly influenced by location.

BackgroundOxidative stress due to abnormal induction of reactive oxygen species (ROS) molecules is believed to be involved in the etiology of many diseases. Evidences suggest that ROS is involved in nephrotoxicity through frequent exposure to industrial toxic agents such as thioacetamide (TAA). The current investigation was designed to explore the possible protective effects of the leaves of Vitex negundo(VN) extract against TAA-induced nephrotoxicity in rats.MethodsTwenty four Sprague Dawleyrats were divided into four groups: (A) Normal control, (B) TAA (0.03% w/v in drinking water), (C) VN100 (VN 100 mg/kg + TAA) and (D) VN300 (VN 300 mg/kg + TAA). Blood urea and serum creatinine levels were measured,supraoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels of renal tissue were assayed. Histopathological analysis together with the oxidative stress nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox in kidney sections were examined in all experimental groups.ResultsBlood urea and serum creatinine levels were increased in TAA group as a result of the nephrotoxicity compared to the VN100 and VN300 groups where, the levels were significantly decreased (p < 0.05). Renal MDA level was significantly decreased (p < 0.05) in the VN-treated groups with increased CAT and SOD activities compared to the TAA group. Light microscopic examination of renal tissues stained by H&E stain and Masson’s Trichrome for TAA-treated groups revealed severe histopathological changes, whereas specimens obtained from VN-treated groups showed only mild changes. These findings were supported by immunohistochemical results.ConclusionsVN extract acts as a natural potent antioxidant to prevent ongoing TAA-induced nephrotoxicity in rats, both biochemically and morphologically.

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OBJECTIVES:Genistein is known to influence reproductive system development through its binding affinity for estrogen receptors. The present study aimed to further explore the effect of Genistein on the development of the reproductive system of experimental rats.METHODS:Eighteen post-weaning female Sprague Dawley rats were divided into the following groups: (i) a control group that received vehicle (distilled water and Tween 80); (ii) a group treated with 10 mg/kg body weight (BW) of Genistein (Gen 10); and (iii) a group treated with a higher dose of Genistein (Gen 100). The rats were treated daily for three weeks from postnatal day 22 (P22) to P42. After the animals were sacrificed, blood samples were collected, and the uteri and ovaries were harvested and subjected to light microscopy and immunohistochemical study.RESULTS:A reduction of the mean weekly BW gain and organ weights (uteri and ovaries) were observed in the Gen 10 group compared to the control group; these findings were reversed in the Gen 100 group. Follicle stimulating hormone and estrogen levels were increased in the Gen 10 group and reduced in the Gen 100 group. Luteinizing hormone was reduced in both groups of Genistein-treated animals, and there was a significant difference between the Gen 10 and control groups (p<0.05). These findings were consistent with increased atretic follicular count, a decreased number of corpus luteum and down-regulation of estrogen receptors-α in the uterine tissues of the Genistein-treated animals compared to the control animals.CONCLUSION:Post-weaning exposure to Genistein could affect the development of the reproductive system of ovarian-intact experimental rats because of its action on the hypothalamic-pituitary-gonadal axis by regulating hormones and estrogen receptors.

BackgroundTo investigate the potential protective effects of Tualang honey against the toxicity effects induced by Bisphenol A (BPA) on pubertal development of ovaries.MethodsThis study was conducted on pre-pubertal female Sprague Dawley rats. Animals were divided into four groups (n = 8 in each group). Group I was administered with vehicle 0.2 ml of corn oil (Sigma-Aldrich, USA) using oral gavage daily for six weeks; these animals served as negative control (CO group), Group II was administered with BPA suspended in corn oil at 10 mg/kg body weight and served as positive control (PC group), Group III was administered with 200 mg/kg body weight of Tualang honey 30 min before the administration of BPA at 10 mg/kg (TH group) while Group IV was administered with 200 mg/kg body weight of Tualang honey 30 min before the administration of corn oil (THC group). Body weight of all animals were monitored weekly.ResultsThe BPA-exposed animals exhibited disruption of their estrus cycle, while those animals treated with BPA together with Tualang honey, exhibited an improvement in percentage of normal estrous cycle. Their ovaries had lower numbers of atretic follicles compared to the PC group but higher than the CO group.ConclusionsTualang honey has a potential role in reducing BPA-induced ovarian toxicity by reducing the morphological abnormalities of the ovarian follicles and improving the normal estrous cycle.

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The cranial suspensory ligament (CSL) is a fibromuscular structure anchoring the embryonic gonad to the posterior abdominal wall in male and female mammals. Its persistence in females is believed to be responsible for retaining the ovaries within the abdomen, while its regression in males permits testis descent. Embryonic loss of the CSL in males is believed to be an androgen-dependent event, and failure of this process has been proposed as a cause of cryptorchidism. The present study demonstrates that the nuclei of mesenchymal cells in the caudal part of the CSL are immunoreactively positive for androgen receptor. We examined the effects of exposure of the non-steroidal antiandrogen flutamide during the period from gestational day 10 to birth on the development of the CSL and on testis descent. Exposure of male Albino Swiss rats to the antiandrogen flutamide during this period resulted in feminization of the external genitalia and the suppression of growth of the testes and male reproductive tracts. In adulthood, testes were found to be located in diverse positions including normal scrotal (50%), intra-abdominal (10%) and ectopic suprainguinal (40%). The CSL of the testis persisted into adulthood in all flutamide-treated males, regardless of testis location. In all cases, the ligament consisted of bundles of smooth muscle fibres in the retroperitoneal fat of the posterior abdominal wall. These findings suggest that androgen blockade during embryonic development interferes with testicular descent, but that maldescent cannot be correlated with either the persistence of the CSL of the testis or its structure.

The antifibrotic effects of traditional medicinal herb Caesalpinia sappan (CS) extract on liver fibrosis induced by thioacetamide (TAA) and the expression of transforming growth factor β1 (TGF-β1), α-smooth muscle actin (αSMA), and proliferating cell nuclear antigen (PCNA) in rats were studied. A computer-aided prediction of antioxidant and hepatoprotective activities was primarily performed with the Prediction Activity Spectra of the Substance (PASS) Program. Liver fibrosis was induced in male Sprague Dawley rats by TAA administration (0.03% w/v) in drinking water for a period of 12 weeks. Rats were divided into seven groups: control, TAA, Silymarin (SY), and CS 300 mg/kg body weight and 100 mg/kg groups. The effect of CS on liver fibrogenesis was determined by Masson's trichrome staining, immunohistochemical analysis, and western blotting. In vivo determination of hepatic antioxidant activities, cytochrome P450 2E1 (CYP2E1), and matrix metalloproteinases (MPPS) was employed. CS treatment had significantly increased hepatic antioxidant enzymes activity in the TAA-treated rats. Liver fibrosis was greatly alleviated in rats when treated with CS extract. CS treatment was noted to normalize the expression of TGF-β1, αSMA, PCNA, MMPs, and TIMP1 proteins. PASS-predicted plant activity could efficiently guide in selecting a promising pharmaceutical lead with high accuracy and required antioxidant and hepatoprotective properties.