Male reproductive toxicity and b-luteinizing hormone gene expression in sexually mature and immature rats exposed to 2-bromopropane

1999 ◽  
Vol 18 (11) ◽  
pp. 683-690 ◽  
Author(s):  
X Wu ◽  
A S Faqi ◽  
J Yang ◽  
X Ding ◽  
X Jiang ◽  
...  

1 The reproductive effects of 2-bromopropane (2-BP) in sexually mature and immature male Sprague-Dawley rats were investigated. The animals were randomly divided into three treatment groups and one control group each of which comprised six mature and six immature rats. The treated groups were injected s.c. 200, 600 and 1800 mg/kg of 2-BP on 5 days a week for 5-7 weeks and the control group received the vehicle. 2 The absolute and relative testis weights were significantly reduced in 600 and 1800 mg/kg b.w. dose groups in both mature and immature rats. The absolute epididymis, prostate, seminal vesicle, and pituitary weights and the relative epididymis weights, however, were significant only at the highest dose level used in both mature and immature rats. 3 The sperm concentration and sperm viability in epididymal duct decreased and the percentage of abnormal sperm increased in a dose-dependent manner in both mature and immature rats. Additionally, serum testosterone level was significantly decreased in all dose groups in mature rats, and was significantly reduced only in the group treated with the middle and highest dose in immature rats. 4 In both mature and immature rats treated with 200 and 600 mg/kg, the seminiferous tubules were atrophied and all types of germ cells were decreased in number. At the highest dose level, the effect was more marked showing severely atrophied seminiferous tubules and a complete loss of all types of germ cells. 5 The mating, pregnancy and fertility indices were significantly reduced in the 600 and 1800 mg/kg groups. Additionally, at the highest dose group the number of implantations and viable fetuses per litter were reduced and the resorption rate was increased significantly. 6 In the mature rats, the b-LH gene expression increased significantly in the 1800 mg/kg group when compared to the control group. 7 It can be concluded that 2-BP induces alterations in both neuro-endocrine axis and the reproductive tract under the present experimental conditions. The no observed adverse effect level (NOAEL) in this study could be estimated to be lower than 200 mg/kg/b.w. based on the alteration in testicular morphology as well as on sperm parameters observed at the dose level of 200 mg/kg.

Reproduction ◽  
2014 ◽  
Vol 148 (6) ◽  
pp. H1-H9 ◽  
Author(s):  
Mai Shinomura ◽  
Kasane Kishi ◽  
Ayako Tomita ◽  
Miyuri Kawasumi ◽  
Hiromi Kanezashi ◽  
...  

Cell ablation technology is useful for studying specific cell lineages in a developing organ in vivo. Herein, we established a novel anti-Müllerian hormone (AMH)-toxin receptor-mediated cell knockout (Treck) mouse line, in which the diphtheria toxin (DT) receptor was specifically activated in Sertoli and granulosa cells in postnatal testes and ovaries respectively. In the postnatal testes of Amh-Treck transgenic (Tg) male mice, DT injection induced a specific loss of the Sertoli cells in a dose-dependent manner, as well as the specific degeneration of granulosa cells in the primary and secondary follicles caused by DT injection in Tg females. In the testes with depletion of Sertoli cell, germ cells appeared to survive for only several days after DT treatment and rapidly underwent cell degeneration, which led to the accumulation of a large amount of cell debris within the seminiferous tubules by day 10 after DT treatment. Transplantation of exogenous healthy Sertoli cells following DT treatment rescued the germ cell loss in the transplantation sites of the seminiferous epithelia, leading to a partial recovery of the spermatogenesis. These results provide not only in vivo evidence of the crucial role of Sertoli cells in the maintenance of germ cells, but also show that the Amh-Treck Tg line is a useful in vivo model of the function of the supporting cell lineage in developing mammalian gonads.


Animals ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2801
Author(s):  
Muhammad Faheem Akhtar ◽  
Ejaz Ahmad ◽  
Ilyas Ali ◽  
Muhammad Shafiq ◽  
Zhe Chen

The current study investigated the effect of inhibin immunization on germ cell numbers (spermatogonia, spermatocytes, round, and elongated spermatids), seminiferous tubules (ST) diameter, Johnsen’s score, epithelial height (μm), luminal tubular diameter (μm), and number of ST per field (ST/field) of Yangzhou goose ganders. Histological evaluation showed apoptosis and regression of testes after inhibin (INH) immunization, with a concomitantly marked reduction in the round and elongated spermatids in the experiment (INH) group compared to the control group. The diameter of seminiferous tubules (ST) and epithelial height (EH) were positively correlated at 181, 200, and 227 days of age. In comparison, luminal tubular diameter (LD) was negatively correlated on day 227 to ST diameter and epithelial height. On day 227, many seminiferous tubules per field (ST/field) were negatively correlated to ST diameter, EH, and LD. INH immunization elevated ST diameter, EH, and LD, while Johnsen’s score and number of ST/field had reciprocal expression. In conclusion, the concomitant effect of INH immunization and seasonality in breeding regressed germ cells and damaged spermatogenesis in seminiferous epithelium Yangzhou ganders.


2007 ◽  
Vol 19 (1) ◽  
pp. 119
Author(s):  
L. Arregui ◽  
R. Rathi ◽  
W. Zeng ◽  
A. Honaramooz ◽  
M. Gomendio ◽  
...  

Testis tissue grafting presents an option for preservation of genetic material when sperm recovery is not possible. Grafting of testis tissue from sexually immature males to immunodeficient mice results in germ cell differentiation and production of fertilization-competent sperm from different mammalian species (Honaramooz et al. 2002 Nature 418, 778–781). However, the efficiency of testis tissue xenografting from adult donors has not been critically evaluated. Spermatogenesis was arrested at meiosis in grafts from mature horses (Rathi et al. 2006 Reproduction 131, 1091–1098) and hamsters (Schlatt et al. 2002 Reproduction 124, 339–346), and no germ cell differentiation occurred in xenografts of adult human testis tissue (Schlatt et al. 2006 Hum. Reprod. 21, 384–389). The objective of this study was to investigate survival and germ cell differentiation of testis xenografts from sexually mature donors of different species. Small fragments of testis tissue from 10 donor animals of 5 species were grafted under the back skin of immunodeficient, castrated male mice (n = 37, 2–6/donor). Donors were pig (8 months old), goat (18 months old and 4 years old) (n = 2), bull (3 years old), donkey (13 months old), and rhesus monkey (3, 6, 11, and 12 years old). At the time of grafting, donor tissue contained elongated spermatids, albeit to different degrees (>75% of seminiferous tubules in testis tissue from pig, goat, bull, and 6–12-year-old monkeys, and 33 or 66% of tubules in tissue from donkey or 3-year-old monkey, respectively). Grafts were recovered <12 weeks (n = 14 mice), 12–24 weeks (n = 16 mice), and >24 weeks (n = 7 mice) after grafting and classified histologically as completely degenerated (no tubules found), degenerated tubules (only hyalinized seminiferous tubules observed), or according to the most advanced type of germ cell present. Grafts from pig, goat, bull, and 6–12-year-old monkeys contained >60% degenerated tubules or were completely degenerated at all time points analyzed. In contrast, in grafts from the 3-year-old monkey, only 18% of tubules were degenerated, 14% contained Sertoli cells only, 64% contained meiotic, and 4% haploid germ cells at 24 weeks after grafting. Similarly, donkey testis grafts recovered 12–24 weeks after grafting contained <2% degenerated tubules, 46% of tubules had Sertoli cells only, 45% contained meiotic, and 7% haploid germ cells. These results show that survival and differentiation of germ cells in testis grafts from sexually mature mammalian donors is poor. However, better graft survival and maintenance of spermatogenesis occurred in donor tissue from donkey and 3-year-old monkey that were less mature at the time of grafting. Therefore, species and age-related differences appear to exist with regard to germ cell survival and differentiation in xenografts from adult donors. This work was supported by USDA/CSREES 03-35203-13486, NIH/NCRR 5-R01-RR17359-05, the Spanish Ministry of Education, and Science (BES-2004-4112).


2009 ◽  
Vol 25 (1) ◽  
pp. 41-47 ◽  
Author(s):  
G Yu ◽  
Q Guo ◽  
L Xie ◽  
Y Liu ◽  
X Wang

The aim of this study is to investigate the effects of subchronic exposure to carbendazim on spermatogenesis and fertility in male rats. Ninety-eight healthy male rats were divided into four groups: three exposure groups and a control group. Carbendazim was administered orally to male rats at 0, 20, 100 and 200 mg/kg for 80 days prior to mating. Each male was cohabited with an unexposed female for a maximum of 5 days. In 100 and 200 mg/kg groups, the mating index was relatively increased, the fertility index was decreased, and the testis weight, the sperm counts and motility were also decreased. The levels of luteinizing hormone (LH) showed a decreasing tendency and there was a statistical difference between the 200 mg/kg group and the control group. There were no obvious effects on the levels of follicle stimulating hormone (FSH) and testosterone (T). Histopathological evaluation showed atrophic seminiferous tubules, decreased germ cells, and increased sloughing of germ cells. Flow cytometric analysis of the testicular tissue revealed that carbendazim inhibited meiotic transformation and interfered with the spermatogenic process. These results suggest that carbendazim has adverse effects on spermatogenesis, resulting in reduced fertility in male rats.


2013 ◽  
Vol 19 (S4) ◽  
pp. 47-48
Author(s):  
M. Ferreira ◽  
T.M. Santos ◽  
M.L. Pereira

Cr(III)-tris(picolinate), [Cr(pic)3], is a very common dietary supplement, recommended for humans, cattle and swine. Chromium is considered an essential trace element, when in oxidation state +3, with some of its compounds seeming to have a beneficial effect on blood sugar regulation mechanisms. However, the safety of the use of a particularly popular Cr(III) compound, ie [Cr(pic)3], remains debatable. Clastogenic, and mutagenic features have been reported by Stearns and co-workers, although surrounded by a controversial and contradictory multitude of publications on this subject. The present work aims to study the effects of [Cr(pic)3] on mice spermatogenesis.Cr(III)-tris(picolinate) was synthesized and characterized according to the literature. Its composition as a mononuclear complex was tested by ESI-MS and by X-ray powder diffraction followed by single-crystal simulation calculations.Male adult CDI mice from Harlan (Spain) were divided in groups and orally given 25 mg/kg and 50 mg/kg/body weigh/daily of [Cr(pic)3] for two weeks. Controls were also done. Behaviour and body weight were monitored throughout the experiments. After sacrifice, testis were collected, weighed, and fixed in Bouin´s solution. Organs were then prepared for histology using routine techniques. Animal experiments were conducted according to ethics procedures. Histological sections of control group evidenced normal regular features (Fig. 1a). However considerable damage was observed in both experimental groups in a dose dependent manner. In fact, seminiferous tubules showed degenerative changes within epithelium, namely vacuolation and sloughing of immature germ cells into the lumen in the group given the lowest dose (Fig.1 b,c). The high dosed group displayed more conspicuous injury within testis, namely strongly atrophic seminiferous tubules devoid of germs cells and strong vacuolation (Figs.1d-f).The results of this study have shown an increased risk of adverse events in mice receiving 50 mg/kg/body weight of [Cr(pic)3]. However, little potential for adverse reproductive and developmental effects namely on progeny was recently described for male mice fed a diet containing 200 mg/kg/day [Cr(pic)3]. In conclusion, concerns about using dietary supplements based on [Cr(pic)3] remain to be elucidated in future work.This work was financed by CICECO, Aveiro University, Portugal.


1972 ◽  
Vol 71 (2) ◽  
pp. 393-408 ◽  
Author(s):  
Morio Yamada ◽  
Shunji Yasue ◽  
Keishi Matsumoto

ABSTRACT In the incubation study of [3H] testosterone with tissue homogenates in the presence of NADPH, it was shown that the rate of production of the sum of all 5α-reduced products by 30-day-old rat testes (50 to 100 nmoles/g tissue or 100 mg protein/h) was of the order of twenty times that by the ventral prostate (2 to 4 nmoles/g tissue/h). The activities of the C19-steroid Δ4-5α-reductase of the seminiferous tubules, germ cells and tubular non-germ cells isolated from immature rats (7 to 10, 11 to 13 and 5 to 7 nmoles/100 mg protein/h, respectively) were of similar order to those of the prostate, while much less activity was found in the spleen and muscle. It was also noted that the activity of the 5α-androstane-3α-, and -3β-hydroxysteroid dehydrogenase seemed to be higher in each tissue of immature rat testes than in the prostate tissue. The seminiferous tubules were isolated by collagenase treatment and germ cells were separated from non-germ cells by tubular cell culture at 34°C for 2 days. Thus, germ cells of immature rat testes seem to have the characteristics of androgen responsive tissue.


Reproduction ◽  
2015 ◽  
Vol 149 (3) ◽  
pp. 259-268 ◽  
Author(s):  
Himesh Makala ◽  
Lavanya Pothana ◽  
Surabhi Sonam ◽  
Ashwini Malla ◽  
Sandeep Goel

Ectopic autografting of testis tissue is a promising approach for studying testicular development, male germline preservation and restoration of male fertility. In this study, we examined the fate of various testicular cells in adult mouse testes following ectopic autografting at 1, 2, 4 and 8 weeks post grafting. Histological examination showed no evidence of re-establishment of spermatogenesis in autografts, and progressive degeneration of seminiferous tubules was detected. Expression of germ cell-specific proteins such as POU5F1, DAZL, TNP1, TNP2, PRM1 and PRM2 revealed that, although proliferating and differentiating spermatogenic germ cells such as spermatogonia, spermatocytes and spermatids could survive in autografts until 4 weeks, only terminally differentiated germ cells such as sperm persisted in autografts until 8 weeks. The presence of Sertoli and peritubular myoid cells, as indicated by expression of WT1 and ACTA2 proteins, respectively, was evident in the autografts until 8 weeks. Interestingly, seminal vesicle weight and serum testosterone level were restored in autografted mice by 8 weeks post grafting. The expression of Leydig cell-specific proteins such as CYP11A1, HSD3B2 and LHCGR showed revival of Leydig cell (LC) populations in autografts over time since grafting. Elevated expression of PDGFRA, LIF, DHH and NEFH in autografts indicated de novo regeneration of LC populations. Autografted adult testis can be used as a model for investigating Leydig cell regeneration, steroidogenesis and regulation of the intrinsic factors involved in Leydig cell development. The success of this rodent model can have therapeutic applications for adult human males undergoing sterilizing cancer therapy.


2019 ◽  
Vol 8 ◽  
Author(s):  
Saeed Sadeghi ◽  
Mahdi Jalali ◽  
Mohammad Reza Nikravesh ◽  
Mojtaba Sankian

Background: Hyperthyroidism is one of the disorders of the thyroid gland, an organ that controls the cellular and molecular behaviors of the seminiferous tubule basement membrane (BM), and ultimately, influences its evolutionary process. We aimed to investigate the effects of hyperthyroidism on immunohistochemical characteristics and gene expression levels of collagen IV and laminin-α5 in seminiferous tubules BM of Balb/C mice. Materials and Methods: Twenty male Balb/C mice were divided into experimental and control groups. The experimental group received 500 mg/l of levothyroxine (L-thyroxine) diluted in drinking water for two months to inducing hyperthyroidism, which was confirmed by radioimmunoassay. At the end of the study, the mice were sacrificed, and their testes were extracted for immunohistochemistry and real-time polymerase chain reaction assays. Results: Although a weak reaction was observed in the experimental specimens, no significant enhancement was noted in color intensity of type IV collagen in the seminiferous tubules BM of the experimental group as compared to the control group (P>0.05). Collagen IV gene expression results in the experimental group were not significantly different from the controls (P>0.05). Thus, there was a significant increase in laminin α5 gene expression compared to the control group (P=0.016). Conclusion: Considering the key role of collagen IV and laminin-α5 in the seminiferous tubule BM in the testes, the results of this study indicated that hyperthyroidism has important effects on both structures and functions of these two components. [GMJ.2019;8:e1369]


2021 ◽  
Author(s):  
Ifukibot Levi Usende ◽  
Fatima Oyenike Oyelowo ◽  
Agbonu Oluwa Adikpe ◽  
Benjamin Obukowho Emikpe ◽  
Allam Abdel Hamid Mohamed Nafady ◽  
...  

Abstract Environmental exposure to vanadium has been on the increase in recent time. This metal is a known toxicant. The current study was conducted to investigate the reproductive toxicity of sodium metavanadate (SMV) in male African giant rats. Administration of SMV was done intraperitoneally daily for 14 consecutive days at a dosage of 3mg/kg body weight. Sterile water was administered to the control group. We analyzed serum reproductive hormones, sperm reserve and quality as well as testicular ultrastructural changes following SMV treatment. Our results showed SMV exposed AGR group had statistically increased progesterone but decreased testosterone, FSH and LH concentrations. Also, SMV treated group had statistically decreased sperm motility and mass activity with increased percentage of abnormal morphophenotypes of spermatozoa and upregulation of P53 immunopositive cell. Ultrastructural study revealed vocuolation of germ and Sertoli cells, cytoplasmic and nucleus; and mitochondrial swelling and vacuolations were also observed. There was severe disintegration of the seminiferous tubules, atrophy and degeneration of myeloid cells and apoptosis of the Leydig, Sertoli and germ cells. In conclusion, intraperitoneal SMV exposure exerts severe adverse effects on some serum reproductive hormones, reduction of sperm reserve and quality, apoptosis and degenerative changes of the Leydig, Sertoli and germ cells which can lead to infertility.


Co-administration of bleomycin, etoposide, and cisplatin (BEP) becomes standart chemotherapy for testicular cancer because it has brought a cure rate of more than 90%. Impact of the treatment to the outcome become a concern, particularly the adverse effect on a long-term reproductive health risk to cancer survivors. There is no evidence, when the damage to the testes began due to the administration of BEP chemotherapy, makes the indication of treatment still controversial. The aim of this study is to determine the effects of BEP on Spermatogonial cell and MDA levels outcome in an animal model. Male wistar rats (Rattus norvegicus) aged 13-15 weekswere treated daily with BEP for three cycles, 33 hours each. It was divided into one control group received 1cc of normal saline, and three groups received three cycles of 0.5 x dose-levels of BEP (Intraperitoneally; 0.75 mg/kg, 7.5 mg/kg, and 1.5 mg/kg). Cell number of Spermatogonia cells were calculated from HE-stained specimens and observed under light microscope (Olympus BX-51) using 400x magnification (high power field) Thiobarbituric acid (TBA) test method used to measure malondialdehyde (MDA) level by spectrophotometry. The result was a significant decrease in the average number of Spermatogonia cells (p = 0.003) between the control group and others. This is caused by excessive exposure to BEP chemotherapy, which cause atrophy of the seminiferous tubules and content of germ cells in the tubules has decreased, accompanied by the appearance of immature germ cells that enter the lumen. A significant increase in MDA levels (p = 0.001) occurred after the administration of the third cycle of BEP chemotherapy. In conclusion, BEP chemotherapy adversely affect the number of Spermatogonia cells and MDA level. The third cycle BEP chemotherapy significantly more destructive compared to the first and second cycle.


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