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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (20 March 2026) | Viewed by 4853

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Special Issue Editor

Dr. Maria Cristina Budani

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Department of Medical, Oral and Biotechnologies Sciences, University “G. d’Annunzio” of Chieti—Pescara, 66100 Chieti, Italy
Interests: assisted reproductive techniques; cigarette smoke; embryology; fertility; endocrine disruptors; molecular mechanisms; reproductive toxicology; teratology

Special Issue Information

Dear Colleagues,

The aim of the Special Issue, entitled “Novel insights into reproductive toxicology”, is to update our knowledge of the possible toxicants capable of inducing ovarian toxicity, as well as its underlying molecular mechanisms. It has been known that the ovary represents a susceptible target for toxic compounds. Environmental substances, including pesticides, heavy metals, solvents and other pollutants, can represent a severe hazard for healthy ovarian functionality. Additionally, lifestyle habits such as smoking cigarettes, alcohol consumption, and the intake of certain drugs, foods and xenobiotics with gonadotoxic effects—including plastic components of resin containers used for food and drinks—may negatively influence female fertility.

Furthermore, an additional aim of the present Special Issue is to update the experimental data concerning the effects of possible teratogens and drug-induced birth defects. It is noteworthy that the current advancements in teratogenesis and the use of integrated molecular approaches (combination of transcriptomics and metabolomics, in addition to morphological evaluations) have enabled the considerable addition of information on the mechanisms of teratogenicity over the last decade. In view of the profound clinical relevance of this topic, experimental data in this perspective are needed.

Dr. Maria Cristina Budani
Guest Editor

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Keywords

endocrine disruptors
environmental toxicants
fertility
heavy metals
lifestyle habits
molecular mechanisms
pregnancy
teratology
teratogenic compounds
reproductive toxicology

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Published Papers (4 papers)

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27 pages, 1017 KB

Open AccessArticle

Bisphenol A in the Urine: Association with Urinary Creatinine, Impaired Kidney Function, Use of Plastic Food and Beverage Storage Products but Not with Serum Anti-Müllerian Hormone in Ovarian Malignancies

by Mateja Sladič, Špela Smrkolj, Gorazd Kavšek, Senka Imamovic-Kumalic, Ivan Verdenik and Irma Virant-Klun

Int. J. Mol. Sci. 2025, 26(10), 4811; https://doi.org/10.3390/ijms26104811 - 17 May 2025

Cited by 2 | Viewed by 2479

Abstract

Bisphenol A (BPA) is a high-production-volume industrial chemical and component of commonly used plastic products. However, it is also an endocrine-disrupting chemical that can negatively affect human health. It is not yet known whether it is associated with the development of epithelial ovarian cancer (EOC), a severe and highly fatal human disease. Therefore, the purpose of this study was to determine the concentrations of BPA in the urine of women with EOC or epithelial borderline ovarian tumors (EBOTs) using gas chromatography tandem mass spectrometry (GC-MS/MS) and find their possible associations with kidney function at the molecular level, urine and blood biochemical parameters related to metabolism, anti-Müllerian hormone (AMH) (a marker of ovarian reserve/fertility), and lifestyle habits determined via a questionnaire in comparison to healthy controls. The results suggest that the unadjusted or urine-specific-gravity-adjusted BPA levels were significantly increased in women with EOC/EBOT. The unadjusted BPA was significantly positively associated with urinary creatinine (p = 0.007) in all women with EOC/EBOT after adjustment for age, body mass index, and pregnancy using multiple linear regression analysis. This may be related to kidney injury. However, no association was found between urinary BPA and serum AMH levels in women. Women with ovarian malignancies were more exposed to plastic products for storing foods and drinks. Some lifestyle habits, including refilling plastic bottles, correlate with higher urinary BPA levels across the entire cohort of women. When considering EOC or EBOT, it is necessary to consider the potential higher exposure of women to BPA, as reflected in their urine and lifestyle habits. Full article

(This article belongs to the Special Issue Novel Insights into Reproductive Toxicology)

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19 pages, 280 KB

Open AccessArticle

Metabolic Determinants of PCSK9 Regulation in Women with Polycystic Ovary Syndrome: The Role of Insulin Resistance, Obesity, and Tobacco Smoke Exposure

by Justyna Niepsuj, Agnieszka Piwowar, Grzegorz Franik and Anna Bizoń

Int. J. Mol. Sci. 2026, 27(1), 331; https://doi.org/10.3390/ijms27010331 - 28 Dec 2025

Cited by 1 | Viewed by 642

Abstract

The aim of this study was to examine associations involving serum proprotein convertase subtilisin/kexin type 9 (PCSK9) in metabolic disturbances observed in women with polycystic ovary syndrome (PCOS), with particular emphasis on the potential impact of tobacco smoke exposure. The study included 88 women: 60 with PCOS (23 smokers and 37 non-smokers) and 28 without PCOS. Selected biochemical and molecular biomarkers related to lipid metabolism, oxidative stress, and inflammation were assessed. No significant differences in PCSK9 levels were observed among non-smoking women with PCOS, smoking women with PCOS, and non-smoking women without PCOS. However, in women with PCOS, excess body weight and insulin resistance were associated with increased PCSK9 concentrations. Significant correlations between PCSK9, lipid profile parameters, and the Castelli and triglycerides-glucose indices suggest a potential role of PCSK9 as a biomarker of dyslipidemia and cardiometabolic risk. Elevated PCSK9 levels may contribute not only to increased low-density lipoprotein cholesterol but also to enhanced formation of oxidized low-density lipoprotein, which is particularly detrimental to cardiovascular and metabolic health. Vitamin D levels were more strongly associated with smoking status and insulin resistance than with excess body weight. Overall, these findings indicate that PCSK9 regulation in PCOS may be driven predominantly by metabolic factors rather than PCOS status or smoking per se, and that metabolic status and vitamin D deficiency should be considered when assessing cardiometabolic risk in this population. Full article

(This article belongs to the Special Issue Novel Insights into Reproductive Toxicology)

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13 pages, 2365 KB

Open AccessArticle

Impact of Erbium and Gadolinium on Xenopus laevis Embryo Development: A Study of Rare Earth Element Toxicity

by Chiara Fogliano, Simona Di Marino, Giulia Rusciano, Francesca Vignola, Adriana Petito, Paola Venditti, Patrizia Cretì, Chiara Maria Motta, Bice Avallone, Rosaria Scudiero and Rosa Carotenuto

Int. J. Mol. Sci. 2026, 27(7), 2920; https://doi.org/10.3390/ijms27072920 - 24 Mar 2026

Viewed by 469

Abstract

Rare earth elements (REE), such as gadolinium (Gd) and erbium (Er), are increasingly recognised as emerging environmental contaminants due to their widespread use in industrial processes, electronics, and medical imaging applications. Despite their extensive presence in aquatic ecosystems, little is known about their developmental toxicity. In this study, Xenopus laevis embryos were exposed to environmentally relevant concentrations of Gd and Er during critical early developmental stages. The assessed endpoints included survival, malformations, growth (body length), and heart rate. Both Gd and Er caused significant sublethal effects, including increased axial malformations, reduced growth, and altered cardiac activity. To explore potential mechanisms of toxicity, the expression patterns of key developmental genes (fgf8, bmp4, sox9, egr2, rax1, pax6) and pro-inflammatory cytokines (tnfα, il1β, p65) were analysed using Real-Time PCR. The results showed dysregulation of gene expression, indicating disruption to pathways involved in morphogenesis and neurodevelopment. Elevated reactive oxygen species levels suggested that oxidative stress was a contributing factor. Raman spectroscopy confirmed biochemical changes affecting proteins, lipids, and nucleic acids, providing evidence of cellular stress and metabolic imbalance. Overall, our findings demonstrate that even low-level exposure to Gd and Er can impair amphibian embryonic development and disturb molecular homeostasis. These results emphasise the ecological risks of REE pollution and highlight the importance of ongoing environmental monitoring and long-term toxicological research. Full article

(This article belongs to the Special Issue Novel Insights into Reproductive Toxicology)

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13 pages, 701 KB

Open AccessArticle

Prenatal Benzydamine Exposure Induces Fetal Growth Restriction and Maternal Oxidative Stress in Rats

by Bianca-Eugenia Ősz, Ruxandra Ștefănescu, Amelia Tero-Vescan, Camil-Eugen Vari, George Jîtcă, Erzsébet Májai and Andreea Sălcudean

Int. J. Mol. Sci. 2026, 27(7), 3005; https://doi.org/10.3390/ijms27073005 - 26 Mar 2026

Viewed by 450

Abstract

Benzydamine is a nonsteroidal anti-inflammatory drug widely used in topical formulations but occasionally misused orally at high doses for psychoactive effects. Data regarding the safety of benzydamine at supratherapeutic doses are limited and mainly focus on central nervous system effects. Even less information is available concerning its safety during pregnancy, despite the increased risk of unplanned pregnancies among users of psychoactive substances. In this preliminary study, we aimed to evaluate the maternal and fetotoxic potential of benzydamine to support future targeted reproductive toxicity investigations. Pregnant Wistar rats received benzydamine throughout gestation, followed by cesarean section and evaluation of fetal viability, fetal body weight at term, and macroscopic abnormalities. Maternal biochemical parameters related to hepatic, renal, and metabolic function, and oxidative stress markers, were also assessed. Results were compared with those of a control group. No significant differences in routine biochemical parameters were observed between groups; however, benzydamine exposure was associated with reduced fetal body weight and increased maternal plasma malondialdehyde levels. These findings suggest that benzydamine may impair fetal growth through indirect maternal toxicity and oxidative stress rather than direct teratogenic effects. Full article

(This article belongs to the Special Issue Novel Insights into Reproductive Toxicology)

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