Pubertal Bisphenol A exposure increases adult rat serum testosterone by resetting pituitary homeostasis

We investigated the effect of bisphenol A (BPA) on oxidative stress and tau-related proteins in adult rat brains. BPA (10 mg/L) was administered to rats for eight weeks through their drinking water. The reactive oxygen species (ROS) scavenging capacity for hydroxyl radicals in the plasma was reduced after two weeks. In the hippocampus, four and eight weeks of BPA increased the ratio of oxidized DJ-1/DJ-1 (PARK7). The ratio of phosphorylated-GSK3β/GSK3β and phosphorylated-AKT/AKT increased after one week of BPA treatment. The ratio of phosphorylated JNK/JNK and phosphorylated-ERK/ERK increased after eight weeks of BPA; the elevation could be related to tau phosphorylation. Protein phosphatase 2A (PP2A) in the hippocampus decreased after eight weeks of BPA treatment. At that time, SOD1 was significantly induced, but no changes in SOD2 expression were apparent in the hippocampus. Furthermore, the ratio of phosphorylated-tau (PHF-1, Ser396/ Ser404) to total tau level did not change. However, PHF-1 or other sites of tau could be phosphorylated after eight weeks in the hippocampi of rats. BPA induced systemic oxidative stress and could change ROS-induced signaling pathways in the brain. These results suggest that mitochondrial dysfunction possibly is not responsible for oxidative stress and neurodegeneration due to low doses of BPA.

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Testicular toxicity of gentamicin in adult rats: Ameliorative effect of lycopene

Human & Experimental Toxicology ◽

10.1177/0960327119864160 ◽

2019 ◽

Vol 38 (11) ◽

pp. 1302-1313 ◽

Cited By ~ 5

Author(s):

HAA Aly

Keyword(s):

Oxidative Stress ◽

Histopathological Examination ◽

Sperm Count ◽

Serum Testosterone ◽

Testicular Toxicity ◽

Adult Rats ◽

Adult Rat ◽

Gentamicin Treatment ◽

Ameliorative Effect ◽

Induced Apoptosis

The current study was aimed to investigate the ameliorative effect of lycopene against gentamicin-induced testicular toxicity in adult rat testes. Pretreatment with lycopene (4 mg/kg/day) significantly prevented the decrease in the absolute testes weight and relative testes weight and the reduction in sperm count, motility, viability, and daily sperm production in gentamicin (100 mg/kg/day)-treated rats. Gentamicin significantly decreased the level of serum testosterone and testicular lactate dehydrogenase-X and G6PDH activities but a marked increase was observed upon pretreatment with lycopene. Testicular caspase-3 and -9 activities were significantly increased but lycopene showed significant protection from gentamicin-induced apoptosis. Oxidative stress was induced by gentamicin treatment as evidenced by increased hydrogen peroxide level and lipid peroxidation and decreased the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities and glutathione content. These alterations were effectively prevented by lycopene pretreatment. Histopathological examination showed loss of spermatogenesis and morphological abnormalities of the testis after treatment with gentamycin. These abnormalities were effectively normalized by pretreatment with lycopene. In conclusion, gentamicin decreases rat testes weight and inhibits spermatogenesis. It induces oxidative stress and apoptosis by possible mitochondrial dysfunction. These data provide insight into the mode of action of gentamicin-induced testicular toxicity and the beneficial role provided by lycopene to restore the suppressed spermatogenesis.

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Bisphenol A alters differentiation of Leydig cells in the rabbit fetal testis

The International Journal of Developmental Biology ◽

10.1387/ijdb.200185hm ◽

2020 ◽

Vol 52 ◽

Author(s):

Alexis Paulina Ortega-García ◽

Verónica Díaz-Hernández ◽

Pedro Collazo-Saldaña ◽

Horacio Merchant-Larios

Keyword(s):

Bisphenol A ◽

Leydig Cells ◽

Serum Testosterone ◽

Disruptive Effect ◽

Paracrine Signaling ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Tissue Compartments ◽

Fetal Organs ◽

The Impact

The endocrine disruptor Bisphenol A (BPA) crosses the placental barrier and reaches the fetal organs, including the gonads. In the testis, fetal Leydig cells (FLC) produce testosterone required for the male phenotype and homeostatic cell-cell signaling in the developing testis. Although it is known that BPA affects cell proliferation and differentiation in FLC, results concerning the mechanism involved are contradictory, mainly due to differences among species. Fast developing fetal gonads of rodents lack cortex and medulla, whereas species with more extended gestation periods form these two tissue compartments. The rabbit provides a good subject for studying the disruptive effect of BPA in fetal Leydig and possible postnatal endocrine consequences in adult Leydig cells. Here, we investigated the impact of BPA administered to pregnant rabbits does, on the FLC population of the developing testes. Using qRT-PCR, we assessed the levels of SF1, CYP11A1, 3β-HSD, and androgen receptor (AR) genes, and levels of fetal serum testosterone were measured by ELISA. These levels correlated with both the mitotic activity and the ultrastructural differentiation of the FLC by confocal and electron microscopy, respectively. Results indicate that BPA alters the expression levels of essential genes involved in androgen paracrine signaling, modifies the proliferation and differentiation of the FLCs, and alters the levels of serum testosterone after birth. Thus, BPA may change the postnatal levels of serum testosterone due to the impaired FLC population formed by the proliferating stem and non-proliferating cytodifferentiated FLC.

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