Elevated congenital anomaly rates and incorporated cesium‐137 in the Polissia region of Ukraine

Wertelecki, Wladimir; Koerblein, Alfred; Ievtushok, Bogdana; Zymak-Zakutnia, N.; Komov, Oleksandr; Kuznietsov, Illia; Lapchenko, Serhiy; Sosyniuk, Zoriana

doi:10.1002/bdra.23476

Cited by 16 publications

(11 citation statements)

References 23 publications

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“…Neural tube defects (NTDs) and eye defects (EDs) are believed to primarily arise from abnormal neural tube closure and disturbed early eye development, which can be caused by certain physical factors (Jablonski, ; Moretti, Bar‐Oz, Fried, & Koren, ; Wertelecki et al, ) and teratogens such as valproic acid (Ehashi et al, ; Tanoshima et al, ) or various industrial and agricultural compounds (Brender & Weyer, ).…”

Section: Introductionmentioning

confidence: 99%

“…In terms of physical factors, several studies already identified the risks of exposure to ionizing radiation during pregnancy and stipulated a causal link with several congenital malformations (reviewed in [De Santis et al, ; Jacquet, ; Verreet, Rangarajan et al, ; Verreet, Verslegers et al, ]). For example, in prenatally irradiated survivors of the Chernobyl disaster, the prevalence of both NTDs (e.g., exencephaly; exposed brain tissue) and EDs (e.g., microphthalmos; reduced eye size) was found to be increased (Burrow et al, ; Wertelecki, ; Wertelecki et al, ). NTDs (26.1/10 000) and microphthalmos (2.5/10 000) have a higher prevalence in the Polissia region (in the Rivne province) as compared to the rest of the Rivne province (respectively 16.4/10 000 and 0.8/10 000 between 2000 and 2009) that was less contaminated with radioisotopes after the Chernobyl disaster (European Surveillance of Congenital Anomalies [EUROCAT] Final Activity Report 2002–2003; Wertelecki, ; Wertelecki et al, ).…”

Section: Introductionmentioning

confidence: 99%

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A detailed characterization of congenital defects and mortality following moderate X‐ray doses during neurulation

Craenen

Verslegers

Buset

et al. 2017

Birth Defects Research

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Background Both epidemiological and animal studies have previously indicated a link between in utero radiation exposure and birth defects such as microphthalmos, anophthalmos, and exencephaly. However, detailed knowledge on embryonic radiosensitivity during different stages of neurulation is limited, especially in terms of neural tube defect and eye defect development. Methods To assess the most radiosensitive stage during neurulation, pregnant C57BL6/J mice were X‐irradiated (0.5 Gy or 1.0 Gy) at embryonic days (E)7, E7.5, E8, E8.5, or E9. Next, the fetuses were scored macroscopically for various defects and prenatal resorptions/deaths were counted. In addition, cranial skeletal development was ascertained using the alcian‐alizarin method. Furthermore, postnatal/young adult survival was followed until 5 weeks (W5) of age, after X‐irradiation at E7.5 (0.1 Gy, 0.5 Gy, or 1.0 Gy). In addition, body and brain weights were registered at adult age (W10) following X‐ray exposure at E7.5 (0.1 Gy, 0.5 Gy). Results Several malformations, including microphthalmos and exencephaly, were most evident after irradiation at E7.5, with significance starting respectively at 0.5 Gy and 1.0 Gy. Prenatal mortality and weight were significantly affected in all irradiated groups. Long‐term follow‐up of E7.5 irradiated animals revealed a reduction in survival at 5 weeks of age after high dose exposure (1.0 Gy), while lower doses (0.5 Gy, 0.1 Gy) did not affect brain and body weight at postnatal week 10. Conclusions With this study, we gained more insight in radiosensitivity throughout neurulation, and offered a better defined model to further study radiation‐induced malformations and the underlying mechanisms.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A detailed characterization of congenital defects and mortality following moderate X‐ray doses during neurulation

Craenen

Verslegers

Buset

et al. 2017

Birth Defects Research

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“…For example, there were higher rates of multiple congenital malformations, trisomy 21, polydactyly, and reduction limb defects in Belarus and regions of Germany; while in Croatia and Turkey they were higher rates of central nervous and neural tube defects (Akar, Cavdar, & Arcasoy, ; Caglayan, Kayhan, Mentesoglu, & Aksit, ; Dolk & Nichols, ; Feshchenko, Schroder, Muller, & Lazjuk, ; Guvenc et al, ; Haeusler, Berghold, Schoell, Hofer, & Schaffer, ; Harjulehto, Aro, Rita, Rytomaa, & Saxen, ; Harjulehto‐Mervaala, Salonen, Aro, & Saxen, ; Hoffmann, ; Irl, Schoetzau, van Santen, & Grosche, ; Kruslin, Jukic, Kos, Simic, & Cviko, ; Lazjuk, Nikolaev, & Novikova, ; Lie et al, ; Little, ; Mocan, Aydemir, Bozkaya, Mocan, & Ozbay, ; Mocan, Bozkaya, Mocan, & Furtun, ; Sperling, Neitzel, & Scherb, ). The Polissia regions of the Ukraine reported higher rates of microcephaly, neural tube defects, and microphthalmia (W. Wertelecki et al, ; Wladimir Wertelecki et al, ; W. Wertelecki et al, ). In contrast to Chernobyl, studies from the 2011 Fukushima Daiichi Nuclear Power Plant disaster in Japan, showed no statistically significant differences in birth defect prevalence between exposed and unexposed areas of Japan (Fujimori et al, ).…”

Section: Discussionmentioning

confidence: 99%

Nuclear radiation and prevalence of structural birth defects among infants born to women from the Marshall Islands

Nembhard

McElfish

Collins

et al. 2019

Birth Defects Research

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Background: With their unique history of exposure to extensive nuclear testing between 1946 and 1958, descendants of Marshall Island residents may have underappreciated genetic abnormalities, increasing their risk of birth defects. Methods: We conducted a retrospective cohort study of resident women with at least one singleton live birth between 1997 and 2013 in northwest Arkansas using state birth certificate data linked to data from the Arkansas Reproductive Health Monitoring System, a statewide birth defects registry. We calculated unadjusted and adjusted prevalence ratios (PR) and 95% confidence intervals (CI) from modified Poisson regression analyses for non-Hispanic (NH) whites, NH-blacks, Hispanics and Marshallese, using NH-whites as the reference group. Results: Of the 91,662 singleton births during the study period, 2,488 were to Marshallese women. Due to the relatively small number of Marshallese births, we could not calculate prevalence estimates for some defects. Marshallese infants had higher rates of congenital cataracts (PR = 9.3; 95% CI: 3.1, 27.9). Although the number of defects was low, Marshallese infants also had higher rates of truncus arteriosus (PR = 44.0; 95% CI: 2.2, 896.1). Conclusions: Marshallese infants may have increased risk of specific birth defects, but estimates are unstable because of small sample size so results are inconclusive.Larger population-based studies would allow for further investigation of this potential risk among Marshallese infants.

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“…Approximately 80% of microphthalmia cases can be explained by pathogenic mutations in SOX2 , OTX2 , PAX6 , VSX2 , RAX , FOXE3 , STRA6 , ALDH1A3 , or RARB [3, 7]. The remaining 20% of microphthalmia cases may be explained by exposure to environmental factors, such as pharmaceuticals (e.g, thalidomide [8]), ionizing radiation exposure [9, 10], fungicide exposure (e.g., benomyl [11]) and gestationally-acquired infections [12], or other factors such as maternal vitamin A deficiency [13, 14]. Blindness or limited vision is observed in individuals with the severest forms of microphthalmia.…”

Section: Introductionmentioning

confidence: 99%

Gclc deletion in surface-ectoderm tissues induces microphthalmia

Thompson

Chen

Philippe

et al. 2019

Preprint

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Glutamate cysteine ligase catalytic subunit (Gclc) is the catalytic subunit for the glutamate-cysteine ligase (Gcl) enzyme. Gcl catalyzes the rate limiting step in glutathione (GSH) synthesis. Gclc is highly expressed in the developing eye. To define the regulatory role of Gclc in eye development, we developed a novel, Le-Cre transgene-driven, Gclc knockout mouse model. Gclc f/f /Le-Cre Tg/mice present with deformation of the retina, cornea, iris, and lens, consistent with a microphthalmia phenotype. Controlling for the microphthalmia phenotype of Gclc wt/wt /Le-Cre Tg/mice revealed that Gclc f/f /Le-Cre Tg/mice have a more severe microphthalmia phenotype. Thus, the loss of Gclc expression exacerbates the microphthalmia phenotype in Le-Cre mice.Gclc f/f /Le-Cre Tg/eyes present with reduced retinal and lens epithelium proliferation and increased lens cell death. Imaging mass spectrometry of ocular tissues revealed changes in the intensity and distribution of several lipid species and proteins in the retina and corneas of Gclc f/f /Le-Cre Tg/eyes. Lastly, using splice-blocking morpholinos and CRISPR/Cas9, we created two gclc knockdown zebrafish models, both of which display a microphthalmia phenotype. Combined, the mouse and zebrafish results indicate that, in chordates, Gclc has a conserved role in regulating eye development. In summary, these novel animal models are useful tools for elucidating the mechanisms involved in microphthalmia development.≈ 11% of the cases [1]. Currently, there is no cure for the severe loss of vision associated with microphthalmia. While surgical treatments exist, they only address the cosmetic abnormalities associated with microphthalmia [15]. However, recent research demonstrating the efficacy of nonsense suppression (inhibiting the effect of a nonsense mutation by pharmacologically increasing the likelihood of a near cognate aminoacyl-tRNA substitution) to rescue lens development when administered postnatally in a Pax6-deficient mouse model has provided hope that treatments for microphthalmia can be developed [16]. Clearly, a more complete understanding of the mechanisms regulating lens development should accelerate the discovery of preventative strategies and/or novel therapeutic treatments for microphthalmia. Glutathione (GSH), an intracellular antioxidant, is highly abundant in the eye, with concentrations of 20mM or more occurring in the lens cortex and epithelium [17, 18]. It is important for physiological detoxification of electrophiles and oxidants in the lens cortex and epithelium [19]. Through these functions, GSH maintains lens clarity and, as such, a decline in GSH levels is associated with cataract development [20, 21]. GSH biosynthesis involves a two-step enzymatic process [22] involving glutamate-cysteine ligase (GCL) followed by glutathione synthase (GSS). GCL, the rate limiting step in GSH synthesis, comprises a catalytic subunit (GCLC) and a modifier subunit (GCLM). Impaired GCLC or GCLM function limits GSH synthesis and reduces intracellular GSH concentrations. Th...

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Elevated congenital anomaly rates and incorporated cesium‐137 in the Polissia region of Ukraine

Cited by 16 publications

References 23 publications

A detailed characterization of congenital defects and mortality following moderate X‐ray doses during neurulation

A detailed characterization of congenital defects and mortality following moderate X‐ray doses during neurulation

Nuclear radiation and prevalence of structural birth defects among infants born to women from the Marshall Islands

Gclc deletion in surface-ectoderm tissues induces microphthalmia

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