Perfluorotridecanoic Acid Inhibits Leydig Cell Maturation in Male Rats in Late Puberty via Changing Testicular Lipid Component

Ochratoxin A is best known as a potent renal carcinogen in male rats and mice after necessarily protracted ingestion, although valid extrapolation to any human disease has not been verified. The hypothesis that the toxin is a cause of human testicular cancer was proposed a decade ago and has proliferated since, partly through incomplete study of the scientific literature. Archived tumorous rat testes were available from Fischer F344 rats exposed to continuous dietary exposure for half of or the whole life in London in the 2000s. Renal cancer occurred in some of these cases and testicular tumours were observed frequently, as expected, in both treated and untreated animals. Application of clinical immunohistochemistry has for the first time consistently diagnosed the testicular hypertrophy in toxin-treated rats as Leydig cell tumours. Comparison is made with similar analysis of tumorous testes from control (untreated) rats from U.S. National Toxicology Program studies, both of ochratoxin A (1989) and the more recent one on Ginkgo biloba. All have been found to have identical pathology as being of sex cord-stromal origin. Such are rare in humans, most being of germinal cell origin. The absence of experimental evidence of any specific rat testicular cellular pathology attributable to long-term dietary ochratoxin A exposure discredits any experimental animal evidence of testicular tumorigenicity. Thus, no epidemiological connection between ochratoxin A and the incidence of human testicular cancer can be justified scientifically.

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The lack of HSD17B3 in male mice results in disturbed Leydig cell maturation and endocrine imbalance akin to humans with HSD17B3 deficiency

The FASEB Journal ◽

10.1096/fj.201902384r ◽

2020 ◽

Vol 34 (5) ◽

pp. 6111-6128

Author(s):

P. Sipilä ◽

A. Junnila ◽

J. Hakkarainen ◽

R. Huhtaniemi ◽

L. Mairinoja ◽

...

Keyword(s):

Leydig Cell ◽

Cell Maturation ◽

Male Mice

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Effect of ETBE on reproductive steroids in male rats and rat Leydig cell cultures

Toxicology Letters ◽

10.1016/j.toxlet.2009.06.879 ◽

2009 ◽

Vol 190 (1) ◽

pp. 74-80 ◽

Cited By ~ 5

Author(s):

Ann de Peyster ◽

Bradley Stanard ◽

Christian Westover

Keyword(s):

Cell Cultures ◽

Leydig Cell ◽

Male Rats ◽

Reproductive Steroids

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Trichloroethylene induced testicular toxicity in rats exposed by inhalation

Human & Experimental Toxicology ◽

10.1191/096032701718620882 ◽

2001 ◽

Vol 20 (11) ◽

pp. 585-589 ◽

Cited By ~ 9

Author(s):

P Kumar ◽

A K Prasad ◽

U Mani ◽

B K Maji ◽

K K Dutta

Keyword(s):

Organic Solvent ◽

Germ Cell ◽

Male Rats ◽

Cell Maturation ◽

Anesthetic Agent ◽

Testicular Toxicity ◽

Human Beings ◽

Histopathological Changes ◽

Dry Cleaning ◽

Testicular Weight

Trichloroethylene (TCE) is an organic solvent used in dry cleaning, metal degreasing, thinner for paints and varnishes, anesthetic agent, and so forth. Human beings are appreciably exposed to TCE vapours by inhalation route. The present study has been undertaken to investigate whether TCE inhalation may also bring about testicular toxic effects. Our results indicate that inhalation of TCE by male rats for 12 and 24 weeks brings about significant reduction in absolute testicular weight, and alters marker testicular enzymes activity associated with spermatogenesis and germ cell maturation, along with marked histopathological changes showing depletion of germs cells and spermatogenic arrest.

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Activity of LH receptor, LH-stimulated cyclic AMP and testosterone production in the Leydig cell of heat-acclimatized rats

Journal of Endocrinology ◽

10.1677/joe.0.1020167 ◽

1984 ◽

Vol 102 (2) ◽

pp. 167-173 ◽

Cited By ~ 3

Author(s):

E. Bedrak ◽

Z. Chap

Keyword(s):

Relative Humidity ◽

Cyclic Amp ◽

Leydig Cell ◽

Male Rats ◽

Heat Acclimatization ◽

Lh Receptor ◽

Hot Environment ◽

C 30 ◽

Lower Capacity ◽

Trophic Hormone

ABSTRACT Key reactions associated with the capacity of the isolated Leydig cell to synthesize testosterone were studied in male rats acclimatized to a hot environment (33–35 °C, 25–40% relative humidity) and controls (20–22 °C, 30–50% relative humidity). The results demonstrate that acclimatization to heat coincides with: (1) a lower number of human chorionic gonadotrophin (hCG) receptors (P<0·01) in the Leydig cell, (2) higher affinity of the Leydig cell for hCG (P < 0·05), (3) lower hCG-stimulated cyclic AMP production (P<0·05) by the Leydig cell and (4) lower capacity of the Leydig cell to synthesize testosterone (P<0·01) after hCG challenge. It is suggested that the major cellular alteration responsible for the decreased testosterone secretion by the Leydig cell lies distal to the step involving the binding of the trophic hormone to its receptor and that heat-acclimatization induces changes in the integrity of the various cellular membranes leading to the impeded function of adenylate cyclase and 17β-hydroxysteroid oxidoreductase. J. Endocr. (1984) 102, 167–173

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The Production of Testosterone and Gene Expression in Neonatal Testes of Rats Exposed to Diisoheptyl Phthalate During Pregnancy is Inhibited

Frontiers in Pharmacology ◽

10.3389/fphar.2021.568311 ◽

2021 ◽

Vol 12 ◽

Author(s):

Bin Ji ◽

Zina Wen ◽

Chaobo Ni ◽

Qiqi Zhu ◽

Yiyan Wang ◽

...

Keyword(s):

Leydig Cell ◽

Corn Oil ◽

Serum Testosterone ◽

Male Rats ◽

Sprague Dawley ◽

Testosterone Levels ◽

Protein Levels ◽

Gestational Exposure ◽

Phthalate Plasticizer ◽

Neonatal Testis

Background: Diisoheptyl phthalate (DIHP) is a phthalate plasticizer, which is a branched phthalate. Here, we reported the effects of gestational exposure to DIHP on testis development in male rats.Methods: Pregnant Sprague-Dawley rats were orally fed with vehicle (corn oil, control) or DIHP (10, 100, 500, and 1,000 mg/kg) from gestational day (GD) 12–21. At GD21, serum testosterone levels, the number and distribution of fetal Leydig cells, and testicular mRNA and protein levels, the incidence of multinucleated gonocytes, and focal testicular hypoplasia in the neonatal testis were measured.Results: DIHP increased the fetal Leydig cell cluster size and decreased the fetal Leydig cell size with LOAEL of 10 mg/kg. DIHP did not affect the fetal Leydig cell number. DIHP significantly lowered serum testosterone levels, down-regulated the expression of steroidogenesis-related genes (Lhcgr, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Hsd17b3) and testis descent-related gene (Insl3) as well as protein levels of cholesterol side-chain cleavage enzyme (CYP11A1) and insulin-like 3 (INSL3). DIHP dose-dependently increased the percentage of multinucleated gonocytes with the low observed adverse-effect level (LOAEL) of 100 mg/kg. DIHP induced focal testicular hypoplasia.Conclusion: Gestational exposure to DIHP causes testis dysgenesis in rats.

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