Fetal and Perinatal Influence of Xenoestrogens on Testis Gene Expression

Saunders, Philippa; Majdič, Gregor; Parte, P.; Millar, Michael; Fisher, Janes S.; Turner, Katie J.; Sharpe, R. M.

doi:10.1007/978-1-4615-5913-9_19

Cited by 55 publications

(24 citation statements)

References 40 publications

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“…Those results suggest that, in the mammalian foetus and in the newborn, the toxicity of BPA and DES is attributable to the low expression of UGT2B1 in the developmental stages of the animal. Curiously, the size of the testis and the diameter of the seminiferous tubules were markedly decreased in newborns exposed to DES but not in those exposed to BPA [40]. In the light of our present results, this phenomenon can be ascribed to the UGT activity, which is much higher towards BPA than that towards DES, as shown by UGT2B1 in the rat liver.…”

Section: Discussionsupporting

confidence: 43%

Glucuronidation of the environmental oestrogen bisphenol A by an isoform of UDP-glucuronosyltransferase, UGT2B1, in the rat liver

Yokota

Iwano

Endo

et al. 1999

Biochemical Journal

153

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Bisphenol A, an environmental oestrogenic chemical, was found to conjugate highly with glucuronic acid in male rat liver microsomes studied in vitro. In the various isoforms tested (1A1, 1A3, 1A5, 1A6, 1A7 and 2B1), glucuronidation of bisphenol A and of diethylstilboestrol, a synthetic crystalline compound possessing oestrogenic activity and known to be glucuronidated by liver microsomes, was catalysed by an isoform of UDP-glucuronosyltransferase (UGT), namely UGT2B1, which glucuronidates some endogenous androgens. UGT activity towards bisphenol A in liver microsomes and in UGT2B1 expressed in yeast AH22 cells (22.9 and 0.58 nmol/min per mg of microsomal proteins respectively) was higher than that towards diethylstilboestrol (75.0 and 4.66 pmol/min per mg of microsomal proteins respectively). UGT activities towards both bisphenol A and diethylstilboestrol were distributed mainly in the liver but were also observed at substantial levels in the kidney and testis. Northern blot analysis disclosed the presence of UGT2B1 solely in the liver, and about 65% of the male rat liver microsomal UGT activities towards bisphenol A were absorbed by the anti-UGT2B1 antibody. These results indicate that bisphenol A, in male rat liver, is glucuronidated by UGT2B1, an isoform of UGT.

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Section: Discussionsupporting

confidence: 43%

Glucuronidation of the environmental oestrogen bisphenol A by an isoform of UDP-glucuronosyltransferase, UGT2B1, in the rat liver

Yokota

Iwano

Endo

et al. 1999

Biochemical Journal

153

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“…These results strongly suggested that NP might have differential effects on Leydig cells to regulate testosterone synthesis. NP and octylphenol are both endocrine disrupting compounds (Isobe et al, 2001;Lu et al, 2007;Saunders et al, 1997;Soto et al, 1991). These environment contaminants have toxic effects on male reproductive system (Murono and Derk, 2002).…”

Section: Discussionmentioning

confidence: 99%

Differential effects of nonylphenol on testosterone secretion in rat Leydig cells

Wu¹,

Wang²,

Wang³

et al. 2010

Toxicology

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“…Interestingly, all of these genes are regulated by the nuclear receptors NR5A1 and NR5A2 (see the section on NR5A). Expression of Nr5a2 is decreased after exposure to DES [72], whereas for Nr5a1, the general consensus is that its expression is not affected by exposure to estrogens [72][73][74][75], although some have reported a decrease in Nr5a1 expression at higher doses [76][77][78]. The deleterious effects of E 2 and DES on FLC differentiation and function are mediated through the nuclear receptor NR3A1, because Nr3a1-deficient male mice are insensitive to these compounds [65,74,79].…”

Section: Estrogen Receptor (Nr3a1)mentioning

confidence: 90%

Nuclear Receptors in Leydig Cell Gene Expression and Function1

Martin

Tremblay

2010

Biology of Reproduction

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Several signals, such as hormones and signaling molecules, have been identified as important regulators of Leydig cell differentiation and function. Conveying these signals and translating them into a genomic response to ensure an accurate physiological output requires the action of a network of transcription factors, including those belonging to the nuclear receptor superfamily. Nuclear receptors regulate expression of genes important for growth, differentiation, development, and homeostasis. Several nuclear receptors, such as steroid hormone receptors (NR3A and NR3C families), are activated upon ligand binding, whereas others, including members of the NR2C, NR2F, and NR4A families, either do not require a ligand or ligands have yet to be identified. Several nuclear receptors (e.g., NR2F2 and NR5A1) have been shown to play essential roles in Leydig cells, whereas for others (e.g., NR2B1 and NR4A1), the assessment of their function has been precluded by the early embryonic lethality associated with null mice or by redundancy mechanisms by other family members. This is now being overcome with the generation of novel approaches, including Leydig cell-specific knockout models. This review provides an overview of the nuclear receptor family of transcription factors as they relate to Leydig cell gene expression and function.

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Fetal and Perinatal Influence of Xenoestrogens on Testis Gene Expression

Cited by 55 publications

References 40 publications

Glucuronidation of the environmental oestrogen bisphenol A by an isoform of UDP-glucuronosyltransferase, UGT2B1, in the rat liver

Glucuronidation of the environmental oestrogen bisphenol A by an isoform of UDP-glucuronosyltransferase, UGT2B1, in the rat liver

Differential effects of nonylphenol on testosterone secretion in rat Leydig cells

Nuclear Receptors in Leydig Cell Gene Expression and Function1

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