FGFR2 inhibition could suppress spermatogenesis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15659-e15659
Author(s):  
Ilya Tsimafeyeu ◽  
Nataliya Lapina ◽  
Mikhail Byakhov ◽  
Nadezhda Dragun ◽  
Evgenia Gavrilova ◽  
...  
Keyword(s):  
Reproductive Tract ◽  
Giant Cells ◽  
Reproductive Age ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Control Group ◽  
Sprague Dawley ◽  
The People ◽  
High Doses ◽  
The Impact

e15659 Background: The incidence of cancer among the people of reproductive age is constantly increasing. Although FGF2/FGFR2 expression in the male reproductive tract has been reported, there is no evidence of the impact of FGFRs inhibitors on sperm function. Therefore, the objective of this large study was to determine the effects of alofanib, selective FGFR2 allosteric extracellular inhibitor on the regulation of sperm physiology using the rat and rabbit models. Methods: Two-hundred forty Sprague-Dawley rats and 30 Chinchilla white rabbits received alofanib (0–40.5 and 0–21.6 mg/kg/day, respectively) intravenously on a consecutive daily dosing schedule for six months. Eighty rats and 8 rabbits were in the control group. The subchronic study evaluated high doses (300 mg/kg/day) of alofanib for 2 months in 15 male rats. Necropsy was conducted following treatment/recovery periods, and histologic examinations were performed. Results: Animals were active. After injections of a dose equivalent to a human therapeutic dose during 6 months, most of the seminiferous tubules were empty, the elements of spermatogenesis were not classified, and altered primary spermatogonia and spermatocytes were distinguished in male rats. After injections of a five-fold dose, all seminiferous tubules were empty and expelled by a cylindrical epithelium. Very similar changes in sperm physiology were founded in rabbits. Most of the seminiferous tubules were blank, and some tubules contained eosinophilic amorphous masses. High doses of alofanib resulted in pronounced atrophy of the spermatogenic tubule epithelium. Multinucleated giant cells were observed in the lumen of a part of the tubules. There were no changes in untreated animals. Conclusions: FGFR2 inhibition led to the suppression of spermatogenesis. Male cancer patients should be informed of this potential adverse event before treatment with FGFR2 inhibitors.

scholarly journals High Doses of Caffeine during the Peripubertal Period in the Rat Impair the Growth and Function of the Testis

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Minji Park ◽  
Yuri Choi ◽  
Hyeonhae Choi ◽  
Ju-Yearn Yim ◽  
Jaesook Roh
Keyword(s):  
Leydig Cells ◽  
Ex Vivo ◽  
Body Weight Gain ◽  
Male Rats ◽  
Male Rat ◽  
Control Group ◽  
High Doses ◽  
And Function ◽  
The Impact ◽  
Caffeine Exposure

Prenatal caffeine exposure adversely affects the development of the reproductive organs of male rat offspring. Thus, it is conceivable that peripubertal caffeine exposure would also influence physiologic gonadal changes and function during this critical period for sexual maturation. This study investigated the impact of high doses of caffeine on the testes of prepubertal male rats. A total of 45 immature male rats were divided randomly into three groups: a control group and 2 groups fed 120 and 180 mg/kg/day of caffeine, respectively, via the stomach for 4 weeks. Caffeine caused a significant decrease in body weight gain, accompanied by proportional decreases in lean body mass and body fat. The caffeine-fed animals had smaller and lighter testes than those of the control that were accompanied by negative influences on the histologic parameters of the testes. In addition, stimulated-testosterone ex vivo production was reduced in Leydig cells retrieved from the caffeine-fed animals. Our results demonstrate that peripubertal caffeine consumption can interfere with the maturation and function of the testis, possibly by interrupting endogenous testosterone secretion and reducing the sensitivity of Leydig cells to gonadotrophic stimulation. In addition, we confirmed that pubertal administration of caffeine reduced testis growth and altered testis histomorphology.

scholarly journals The Impact of Dust and Salt Aerosols of the Aral Sea on the Tissues of Rat Testes in the Experiment

2020 ◽  
Vol 8 (A) ◽  
pp. 452-456
Author(s):  
Assylgul Suleimen ◽  
Roza Yesimova ◽  
Bibigul Rakhimova ◽  
Gulnaz Suleimen ◽  
Aidana Yerubay ◽  
...  
Keyword(s):  
Climate Change ◽  
Reproductive Function ◽  
Aral Sea ◽  
Male Rats ◽  
Chemical Pollution ◽  
Seminiferous Tubules ◽  
Control Group ◽  
Negative Effect ◽  
Histological Characteristics ◽  
The Impact

BACKGROUND: The Aral Sea crisis is recognized as one of the global environmental problems of our time. The extreme environmental situation in the region is caused by massive chemical pollution of the territory for several decades by high doses of pesticides, herbicides, dumping of industrial waste into the rivers that feed the Aral Sea. As a result of the Aral Sea desiccation, aridization of the territory, climate change, and salinization of soil and water occurred. This led to increased mineralization of precipitation, climate change, the spread and deposition of dust on an area of about 25 million hectares. One of the factors in reducing fertile activity in humans is a decrease in spermatogenesis activity. Based on identified trends, WHO is forced to review the main indicators of spermograms in the direction of their reduction. AIM: To study the effect of dust and salt aerosols of the Aral Sea on reproductive function, rat testes were studied after 7 and 24 days of inhalation administration. MATERIAL AND METHODS: Some morphometric parameters of the testes were evaluated: The diameter of the convoluted seminiferous tubules and the thickness of the germinal epithelium. The obtained comparative morphological and histological characteristics of the testes of the control and experimental groups indicate the negative effect of the components of dust and salt aerosols of the Aral Sea on the reproductive function of male rats. RESULTS: The thickness of the epithelial spermatogenic layer in the second group of rats is on average 64.52 μm, which is significantly less compared to the control group (81.3 μm). The thickness of the epithelial spermatogenous layer in the third group is on average within 73.36 μm, which is significantly less than in the control group (81.3 μm), but more than in the group exposed to dust and salt aerosols for 7 days (64, 52 μm). CONCLUSION: The study revealed that the impact of dust and salt aerosols of the Aral Sea leads to a change in the morphological and histological characteristics of the testes of animals. In experimental groups, a decrease in the diameter of the convoluted seminiferous tubule and a decrease in the thickness of the epithelial spermatogenic layer were observed. This indicates the negative effect of the components of dust and salt aerosols of the Aral Sea on the reproductive function of male rats exposed to dust for 7 and 24 days.

scholarly journals The Effect of Single and Triple Testicular Biopsy Using Biopty Gun on Spermatogenesis in Pubertal Rats

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1569
Author(s):  
Tomislav Šušnjar ◽  
Ivana Kuzmić Prusac ◽  
Ivan Švagelj ◽  
Anđela Jurišić ◽  
Tomislav Šušnjar ◽  
...  
Keyword(s):  
Sperm Count ◽  
Semen Analysis ◽  
Study Groups ◽  
Testicular Biopsy ◽  
Male Rats ◽  
Lower Percentage ◽  
Control Group ◽  
Sprague Dawley ◽  
Left Testis ◽  
Significant Difference

Background: The aim of this study was to compare consequences in single and triple testicular biopsy by biopty gun in pubertal rats using histological and immunohistochemical analysis. Methods: Thirty-two Sprague-Dawley male rats were used as the experimental model. The rats were randomly divided into three study groups. The rats from the first group (n = 12) received a single-biopsy of upper pole of the left testis, while the rats from the second group (n = 10) received triple-biopsy of upper and lower poles and lateral surface of left testis. The third group (n = 10) was a control group. On the eightieth day after the biopsy in all rats bilateral orchiectomy and funiculectomy were performed to obtain testicular tissue and sperm for analysis. The consequences of the puncture were observed by pathohistology, immunohistochemistry and semen analysis. Results: The results of the study showed lower percentage of sperm count (14.5 mill/mL vs. 16 mill/mL, p = 0.130), sperm motility (24.6% vs. 32.7%, p > 0.05), abnormal sperm (30% vs. 27%, p > 0.05), atrophic tubules (21% vs. 6%, p < 0.001), volume (1.7 mL vs. 2.28 mL, p < 0.01) and apoptotic index (1.56 vs. 1.19, p = 0.650) in the testes with a triple-biopsy compared to the testes with a single-biopsy. Semen analysis showed a borderline significant difference between the group with triple-biopsy where sperm count was lower than it in the control group (14.5 mill/mL vs. 17.5 mill/mL, p = 0.05). A single-biopsy has little effect on the testis, especially on overall fertility. A triple-biopsy showed higher degree of the testicular damage but without a significant impact on overall fertility. Semen analysis showed that single- and triple-biopsies did not have a significant effect on sperm count, motility and morphology. Conclusion: Biopty gun procedure is a cheap, simple and reliable method for testicular biopsy in rats without a significant effect on sperm count, motility and morphology.

scholarly journals Comparison of Bax and Caspase-3 Protein Expression in Liver Cells following UVB Irradiation for 7 days and Treatment of Pimpinella alpina Molk during 7 and 15 days

2020 ◽  
Vol 19 (2) ◽  
pp. 296-303
Author(s):  
Eni Widayati ◽  
Taufiqurrachman Nasihun ◽  
Azizah Hikma Savitri ◽  
Nurina Tyagita
Keyword(s):  
Protein Expression ◽  
Caspase 3 ◽  
Medical Science ◽  
Liver Cells ◽  
Male Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Control Group Design ◽  
Uvb Irradiation ◽  
The Difference

Objective: The effect of Pimpinela alpina Molk (PaM) on decrease in Bax and Caspase-3 protein expression in liver cells apoptosis have been proven. However, the difference result between 7 and 15 days treatment duration of PaM need to be confirmed. This study aimed to confirm that treatment of PaM during 15 days is more effective decreasing Bax and Caspase-3 protein expression in liver cells following UVB irradiation. Methods: In the post test only control group design, 35 Sprague Dawley male rats, 300 gram body weight were divided into two arms, consisting of three groups respectively. First arm comprise Neg-7, PaM7-100, and PaM7-150. Second arm comprise Neg-15, PaM15-100, and PaM15-150. Nor-G was added as normal control neither exposed to UVB nor PaM treatment. In negative group was only radiated to UVB and PaM groups were exposed to UVB and treatment with 100, and 150 mg PaM per oral for 7 and 15 days respectively. At day 8 (first arm) and 16 (second arm), liver organ was taken and Bax and Caspase-3 protein expression assessed by Immunohistochemical staining method. Result: Post Hoc LSD analysis indicated that Bax and Caspase-3 protein expression in PaM15-100 and PaM15-150 was significant lower compared to that of Nor-G, PaM7-100, and PaM7-150, p < 0.05. Conclusion: Ttreatment of PaM with doses 100 and 150 mg for 15 days was better in decreasing Bax and Caspase-3 protein expression of liver cells following UVB irradiation. Bangladesh Journal of Medical Science Vol.19(2) 2020 p.296-303

Effect of oral administration of carbofuran on male reproductive system of rat

1995 ◽  
Vol 14 (11) ◽  
pp. 889-894 ◽  
Author(s):  
N. Pant ◽  
AK Prasad ◽  
SC Srivastava ◽  
R. Shankar ◽  
SP Srivastava
Keyword(s):  
Body Weight ◽  
Sperm Count ◽  
Reproductive Toxicity ◽  
Giant Cells ◽  
Toxicity Assessment ◽  
Male Rats ◽  
Ventral Prostate ◽  
Seminiferous Tubules ◽  
Effect Level ◽  
Dose Dependent Decrease

1 Carbofuran was administered orally to adult male rats at dose levels of 0.1, 0.2, 0.4 or 0.8 mg kg -1 body weight, 5 d wk-1 for 60 days. A dose dependent decrease was observed in body weight of rats treated with 0.2-0.8 mg carbofuran kg -1 body weight 2 A significant decrease in the weight of epididymides, seminal vesicles, ventral prostate and coagulating glands was observed at various test doses of carbofuran except at the lowest dose. 3 Decreased sperm motility, reduced epididymal sperm count along with increased morphological abnormali ties in head, neck and tail regions of spermatozoa were observed in rats exposed to 0.2, 0.4, or 0.8 mg carbo furan kg-1 body weight. 4 In addition, significant alterations were observed in the activities of marker testicular enzymes viz. sorbitol dehydrogenase (SDH), glucose-6-P-dehydrogenase (G6PDH) (decreased), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GT) (increased) depending on dose. 5 Histologically, the results indicated the toxicity of carbo furan on testes depending on dose. The changes pre dominantly consisted of moderate oedema, congestion, damage to Sertoli cells and germ cells, along with the accumulation of cellular debris and presence of giant cells in the lumen of a few seminiferous tubules which showed disturbed spermatogenesis with the higher doses of carbofuran. 6 These observations determined a no effect level dose of 0.1 mg kg-1 body weight of carbofuran on the biochemi cal and morphological indices studied for male repro ductive toxicity assessment in the rat model. The results of the present study provide first hand information on the reproductive toxicity of carbofuran in male rats.

scholarly journals The effect of prophylactic bilateral salpingectomy on ovarian reserve in patients who underwent laparoscopic hysterectomy

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Shizhuo Wang ◽  
Jiahui Gu
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Reserve ◽  
Premenopausal Women ◽  
Laparoscopic Hysterectomy ◽  
Ovarian Tumors ◽  
Reproductive Age ◽  
Control Group ◽  
Significant Difference ◽  
Bilateral Salpingectomy ◽  
The Impact

Abstract Background Bilateral salpingectomy has been proposed to reduce the risk of ovarian cancer, but it is not clear whether the surgery affects ovarian reserve. This study compares the impact of laparoscopic hysterectomy for benign disease with or without prophylactic bilateral salpingectomy on ovarian reserve. Methods Records were reviewed for 373 premenopausal women who underwent laparoscopic hysterectomy with ovarian reserve for benign uterine diseases. The serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and three-dimensional antral follicle count (AFC) were assessed before surgery and 3 and 9 months postoperatively to evaluate ovarian reserve. Patients were divided into two groups according to whether they underwent prophylactic bilateral salpingectomy. The incidence of pelvic diseases was monitored until the ninth month after surgery. Results There was no significant difference between the two surgery groups in terms of baseline AMH, E2, FSH, LH, and AFC (all P > 0.05). There was no difference in potential bias factors, including patient age, operative time, and blood loss (all P > 0.05). There was also no significant difference between the two groups 3 months after surgery with respect to AMH (P = 0.763), E2 (P = 0.264), FSH (P = 0.478), LH (P = 0.07), and AFC (P = 0.061). Similarly, there were no differences between groups 9 months after surgery for AMH (P = 0.939), E2 (P = 0.137), FSH (P = 0.276), LH (P = 0.07) and AFC (P = 0.066). At 9 months after the operation, no patients had malignant ovarian tumors. The incidences of benign ovarian tumors in the salpingectomy group were 0 and 2.68 % at 3 and 9 months after surgery, respectively, and the corresponding values in the control group were 0 and 5.36 %. The incidences of pelvic inflammatory disease in the salpingectomy group were 10.72 and 8.04 % at 3 and 9 months after surgery, respectively, while corresponding values in the control group were 24.13 and 16.09 %. Conclusions Prophylactic bilateral salpingectomy did not damage the ovarian reserve of reproductive-age women who underwent laparoscopic hysterectomy. Prophylactic bilateral salpingectomy might be a good method to prevent the development of ovarian cancer. Larger clinical trials with longer follow-up times are needed to further evaluate the risks and benefits.

INVESTIGATION OF THE EFFECT OF BLACK SEED OIL ON DIABETES-INDUCED - TESTICULAR DAMAGE: A HISTOPATHOLOGICAL STUDY

2021 ◽  
pp. 29-31
Author(s):  
Seval Kaya ◽  
Yusuf Nergiz ◽  
Firat Asir
Keyword(s):  
Tissue Damage ◽  
Seed Oil ◽  
Histopathological Examination ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Control Group ◽  
Histopathological Study ◽  
Diabetes Group ◽  
Black Seed ◽  
Black Seed Oil

In this study, it was aimed to investigate the protective effect of black seed oil against testicular tissue damage in diabetic rats. A total of 18 male rats were divided into 3 groups, including 6 rats in each group.Groups; control (n=6), diabetes (n=6), diabetes + black seed oil (n=6). A single dose of 45 mg / kg streptozocine (STZ) was injected intraperitoneally to induce diabetes. Diabetes + Black seed oil group: For 56 days, 2.5 ml / kg of black seed oil was administered orally to rats.The rats were sacriced at the end of 56 days. Testicular tissues were taken for routine parafn tissue processing for histopathological examination. Parafn sections were stained with Hematoxylin-Eosin and PAS and examined under a light microscope. Atrophy and degeneration were observed in the seminiferous tubules of diabetic group. Histology of black seed oil group sections were similar to that of control group. A signicant difference was found between the black seed oil group and the diabetes group in terms of blood glucose values. As a result, we think that Black Seed Oil ameliorates to the tissue damage caused by diabetes and the decrease in blood sugar value.

scholarly journals Impact of Ellagic Acid in Bone Formation after Tooth Extraction: An Experimental Study on Diabetic Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Mazen M. Jamil Al-Obaidi ◽  
Fouad Hussain Al-Bayaty ◽  
Rami Al Batran ◽  
Jamal Hussaini ◽  
Goot Heah Khor
Keyword(s):  
Normal Saline ◽  
Ellagic Acid ◽  
Tooth Extraction ◽  
Healing Process ◽  
Diabetic Rats ◽  
Male Rats ◽  
Diabetic Rat ◽  
Control Group ◽  
Tooth Socket ◽  
The Impact

Objectives. To estimate the impact of ellagic acid (EA) towards healing tooth socket in diabetic animals, after tooth extraction.Methods. Twenty-fourSprague Dawleymale rats weighing 250–300 g were selected for this study. All animals were intraperitoneally injected with 45 mg/kg (b.w.) of freshly prepared streptozotocin (STZ), to induce diabetic mellitus. Then, the animals were anesthetized, and the upper left central incisor was extracted and the whole extracted sockets were filled with Rosuvastatin (RSV). The rats were separated into three groups, comprising 8 rats each. The first group was considered as normal control group and orally treated with normal saline. The second group was regarded as diabetic control group and orally treated with normal saline, whereas the third group comprised diabetic rats, administrated with EA (50 mg/kg) orally. The maxilla tissue stained by eosin and hematoxylin (H&E) was used for histological examinations and immunohistochemical technique. Fibroblast growth factor (FGF-2) and alkaline phosphatase (ALP) were used to evaluate the healing process in the extracted tooth socket by immunohistochemistry test.Results. The reactions of immunohistochemistry for FGF-2 and ALP presented stronger expression, predominantly in EA treated diabetic rat, than the untreated diabetic rat.Conclusion. These findings suggest that the administration of EA combined with RSV may have accelerated the healing process of the tooth socket of diabetic rats, after tooth extraction.

scholarly journals Protective Effects of Resveratrol against Chronic Immobilization Stress on Testis

ISRN Urology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Gulsah Bitgul ◽  
Isil Tekmen ◽  
Didem Keles ◽  
Gulgun Oktay
Keyword(s):  
Immobilization Stress ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Stress Group ◽  
Group I ◽  
Stress Application ◽  
Chronic Immobilization Stress

Objective. The aim of this study was to investigate protective effects of resveratrol, a strong antioxidant, against possible negative effects of chronic immobilization stress on testes of male rats histochemically, immunohistochemically, ultrastructurally, and biochemically. Material and Methods. Male Wistar rats were divided into 4 groups (n=7). Group I, control group (C), was not exposed to stress. Group II, stress group (S), was exposed to chronic immobilization stress. In Group III, low dose resveratrol + stress group (LRS), rats were given 10 mg/kg/day resveratrol just before the stress application. In Group IV, high dose resveratrol + stress group (HRS), rats were given 20 mg/kg/day resveratrol just before the stress application. For chronic immobilization stress application animals were put in the plastic tubes (6 cm in diameter, 15 cm in length) during 32 days for 6 hours. All animals were sacrificed 18 hours after the last stress application. Results. Histochemical and ultrastructural investigations showed that in stress group there was germ cell deprivation in seminiferous tubules and increase of connective tissue on interstitial area. No significant changes were seen in low and high dose resveratrol groups. After immunohistochemical investigations, TUNEL (+) and Active Caspase-3 (+) cells were increased in seminiferous tubules of stress group compared with those control group, but they were decreased in low and high dose resveratrol groups. According to biochemically results, MDA, GSH, and testosterone levels in stress group showed no significant difference when compared with those of the other groups. Conclusion. The chronic immobilization stress increases oxidative stress and apoptosis and causes histological tissue damages; resveratrol can minimize the histological damage in testes significantly.

New approach for reproductive toxicity assessment: chromatoid bodies as a target for methylmercury and polychlorinated biphenyls in prepubertal male rats

2020 ◽  
Vol 32 (10) ◽  
pp. 914
Author(s):  
M. S. Garcia ◽  
W. A. Orcini ◽  
R. L. Peruquetti ◽  
J. E. Perobelli
Keyword(s):  
Corn Oil ◽  
Morphological Changes ◽  
Synergistic Effects ◽  
Reproductive Toxicity ◽  
Treated Group ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Control Group ◽  
High Dose ◽  
Long Term Effects

This study investigated the reproductive toxicity of methylmercury (MeHg) and Aroclor (Sigma-Aldrich), alone or in combination, following exposure of prepubertal male rats considering the chromatoid body (CB) as a potential target. The CB is an important molecular regulator of mammalian spermatogenesis, primarily during spermatid cytodifferentiation. Male Wistar rats were exposed to MeHg and/or Aroclor , according the following experimental design: control group, which was administered in corn oil (vehicle) only; MeHg-treated group, which was administered 0.5mg kg−1 day−1 MeHg; Aroclor-treated group, which was administered 1mg kg−1 day−1 Aroclor; Mix-LD, group which was administered a low-dose mixture of MeHg (0.05mg kg−1 day−1) and Aroclor (0.1mg kg−1 day−1); and Mix-HD group, which was administered a high-dose mixture of MeHg (0.5mg kg−1 day−1) and Aroclor (1.0mg kg−1 day−1). MeHg was diluted in distilled water and Aroclor was made up in corn oil (volume 1mL kg−1). Rats were administered the different treatments from PND23 to PND53 by gavage, . The morphophysiology of CBs was analysed, together with aspects of steroid hormones status and regulation, just after the last treatment on PND53. In addition, the long-term effects on sperm parameters were assessed in adult animals. MeHg exposure increased mouse VASA homologue (MVH) protein levels in seminiferous tubules, possibly affecting the epigenetic status of germ cells. Aroclor produced morphological changes to CB assembly, which may explain the observed morphological defects to the sperm flagellum and the consequent decrease in sperm motility. There were no clear additive or synergistic effects between MeHg and Aroclor when administered in combination. In conclusion, this study demonstrates that MeHg and Aroclor have independent deleterious effects on the developing testis, causing molecular and morphological changes in CBs. To the best of our knowledge, this is the first study to show that CBs are targets for toxic agents.

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