Differential effects of urinary and recombinant chorionic gonadotropin on oxidative stress responses in decidualizing human endometrial stromal cells

Kajihara, Takeshi; Tochigi, Hideno; Uchino, Satomi; Itakura, Atsuo; Brosens, Jan J.; Ishihara, Osamu

doi:10.1016/j.placenta.2011.05.002

Cited by 12 publications

(10 citation statements)

References 40 publications

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“…An up-regulation of DNA damage-related genes (especially ribonucleotide reductase 2) within the decidua has been shown, in a mouse model, to promote uterine cell proliferation and decidualization in early pregnancy [37]. Whether this is true also in human pregnancy is not known, although several studies have suggested that the process of decidualization in humans confers protection against oxidative stress-induced cell damage [38] and represses signal transduction pathways that promote oxidative stress-mediated cell death [39]. Regardless, excessive DNA damage at the fetal-maternal interface is likely to be pathogenic.…”

Section: Discussionmentioning

confidence: 99%

In Vivo and In Vitro Evidence for Placental DNA Damage in Preeclampsia

et al. 2014

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Preeclampsia (PE) is an idiopathic multisystem disease affecting 5–7% of pregnant women. Placental oxidative stress is a characteristic feature of PE and occurs when the production of reactive oxygen species (ROS) within the placenta overwhelms the intrinsic anti-oxidant defenses. We hypothesize that excessive oxidative DNA damage at the fetal-maternal interface coupled with a defective DNA damage/repair response is causally related to PE. Here we demonstrate that γH2AX (a sensitive marker of DNA damage) is expressed in the maternal decidua but not trophoblast of normal placentas, and that expression is significantly higher in PE placental tissues in vivo. Using primary in vitro cultures of maternal decidual stromal cells (DSCs) and fetal cytotrophoblast cells (CTs), we show an increase in γH2AX foci in DSCs cultured with vs without H2O2 (70.6% vs 11.6%; P<0.0001) or under hypoxia-reperfusion vs normoxia (20- vs 3-fold; P = 0.01); no foci were seen in CTs. We further demonstrate that Base Excision Repair (BER) intermediates are significantly increased in DSCs (not CTs) under these same conditions. Our data show that DNA damage is significantly more common in PE placentas, and that this DNA damage is localized to the maternal and not fetal side of the placenta. CTs may be selectively resistant to DNA damage in an effort to protect the fetus.

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Section: Discussionmentioning

confidence: 99%

In Vivo and In Vitro Evidence for Placental DNA Damage in Preeclampsia

et al. 2014

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“…Human chorionic gonadotropin is one of the earliest signals secreted by the implanting embryo. Recombinant, but not urinary, human chorionic gonadotropin protected decidualizing human endometrial stromal cells from oxidative cell death through enhancing the expression of manganese superoxide dismutase and selectively limiting activation of the apoptotic machinery in decidualizing human stromal cells (47). Although rodents and humans have a similar hemochorial type of placenta and exhibit similarities in terms of hormonal regulation of gene expression in the uterus, they are different in many aspects.…”

Section: Rrm2mentioning

confidence: 97%

“…The decidual process can confer protection against oxidative stress-induced cell damage (47). During decidualization, FOXO1 may enhance the ability of decidualized cells to prevent oxidative damage, whereas FOXO3a repression can disable the signaling pathway responsible for oxidative cell death (41).…”

Section: Rrm2mentioning

confidence: 99%

Progesterone and DNA Damage Encourage Uterine Cell Proliferation and Decidualization through Up-regulating Ribonucleotide Reductase 2 Expression during Early Pregnancy in Mice

Wei

Deng

et al. 2012

Journal of Biological Chemistry

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Background: Ribonucleotide reductase M2 (RRM2) is a rate-limiting step for DNA synthesis. It is still unknown how RRM2 is involved in decidualization. Results: RRM2 is highly expressed in the decidua and up-regulated by progesterone and DNA damage. Decidualization is significantly inhibited by specific RRM2 inhibitors. Conclusion: RRM2 is essential for mouse decidualization. Significance: This study will shed light on understanding the mechanism underlying decidualization.

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“…These data are particularly important to keep in mind if immunomodulation of hCG would apply in clinical practice (Carbone et al, 2010;Kajihara et al, 2011).…”

Section: We Also O B S E R V E D T H a T H C G I S A B L E T O I N C mentioning

confidence: 99%