Does Ataxia Telangiectasia Mutated (ATM) protect testicular and germ cell DNA integrity by regulating the redox status?

Godschalk, Roger; Vanhees, Kimberly; Maas, L.M.; Drittij, M.-J.; Pachen, D. M. F. A.; Doorn-Khosrovani, Sahar van Waalwijk van Barjesteh; Schooten, Frederik J. van; Haenen, Guido R.M.M.

doi:10.1016/j.reprotox.2016.06.008

Cited by 1 publication

(7 citation statements)

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“…However, when the analysis was performed based on maternal diet only (i.e., pooling the animals with various Atm -ΔSRI genotypes), it appeared that maternal genistein diet significantly increased the level of 8-oxo-dG in the testes from 7.0 ± 2.1 ( n = 18) to 13.2 ± 2.4 ( n = 11) per 10 6 dG ( P = 0.047; Figure 3B ). Maternal genistein diet did not increase DNA damage in the testes of homozygous Atm -ΔSRI mutant mice, because they already had “spontaneously” increased levels of 8-oxo-dG (see Figure 3A ) ( 19 ). Additionally, male Atm -ΔSRI homozygous mice have no production of sperm.…”

Section: Resultsmentioning

confidence: 99%

“…We previously described that the Atm-ΔSRI mutation decreases the production of GSH ( 19 ). Indeed, both the TEAC as well as the concentration of GSH were lower in mice with a maternal control diet that were heterozygous for the Atm -ΔSRI mutation compared to mice with a wild-type genotype ( Figures 5A,B ).…”

Section: Resultsmentioning

confidence: 99%

“…The breeding of mice and sample collection was performed as described previously ( 19 ). Briefly, the parental animals received at 8 weeks of age either normal (control) chow ( n = 8; complete feed for mouse breeding with low-phytoestrogen content lacking both soybean and alfalfa products, resulting in minimal levels of genistein, daidzein, and coumestrol; Ssniff, Soest, Germany) or chow supplemented with genistein ( n = 9; 270 mg/kg feed; LC Laboratories, Woburn, MA, USA) from 3 days before conception until birth of offspring ( Figure 2 ) ( 20 ).…”

Section: Methodsmentioning

confidence: 99%

“…Glucose-6-phosphate dehydrogenase (G6PDH) activity was measured by assessing the conversion of NADP + to NADPH on a Cary 50 UV-vis spectrophotometer (Santa Clara, USA) at 340 nm, using tissue homogenates of the testes in the presence of glucose-6-phosphate ( 19 ). The final incubation mixture consisted of 10 mM of MgCl 2 , 0.7 mM NADP + and 2 mM glucose-6-phosphate, and a Tris-HCl (75 mM) buffer, pH 74 held at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, the aim of this study was to examine the effect of maternal genistein-intake during pregnancy on gene expression of genes involved in the metabolism of estrogens ( Cyp1b1, Comt , and Nqo1) , the antioxidant capacity in testes of male offspring, and the subsequent genetic integrity in sperm. An Atm -ΔSRI animal model ( 19 ) was used to study the additional effect of having a compromised antioxidant and DNA repair system.…”

Section: Introductionmentioning

confidence: 99%

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Maternal exposure to genistein during pregnancy and oxidative DNA damage in testes of male mouse offspring

et al. 2022

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BackgroundGenistein is a dietary supplement with phyto-estrogenic properties. Therefore, high intake of genistein during pregnancy may have adverse effects on the genetic integrity of testes and germ cells of male offspring. In this study, we examined whether maternal exposure to genistein during pregnancy induced oxidative DNA damage in the male germline at adolescence.MethodsAtm-ΔSRI mice have lower glucose-6-phosphate dehydrogenase (G6PDH) activity, which is important for maintaining levels of reduced glutathione and therefore these mice have an increased susceptibility to oxidative stress. Parental heterozygous Atm-ΔSRI mice received a genistein-rich or control diet, after which they were mated to obtain offspring. During pregnancy, mothers remained on the respective diets and after delivery all animals received control diets. Redox status and oxidative DNA damage were assessed in testes and sperm of 12 weeks old male offspring. Gene expression of Cyp1b1, Comt, and Nqo1 was assessed in testes, and DNA methylation as possible mechanism for transmission of effects to later life.ResultsIntake of genistein during pregnancy increased oxidative DNA damage in testes of offspring, especially in heterozygous Atm-ΔSRI mice. These increased DNA damage levels coincided with decreased expression of Comt and Nqo1. Heterozygous Atm-ΔSRI mice had higher levels of DNA strand breaks in sperm compared to wild type littermates, and DNA damage was further enhanced by a genistein-rich maternal diet. G6PDH activity was higher in mice with high maternal intake of genistein compared to control diets, suggesting compensation against oxidative stress. A positive correlation was observed between the levels of DNA methylation and oxidative DNA damage in testes.ConclusionThese data indicate that prenatal exposure to genistein altered gene expression and increased DNA damage in testes and sperm of adolescent male offspring. These effects of genistein on DNA damage in later life coincided with alterations in DNA methylation.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%