Endocrine-Disrupting Chemicals and Reproductive Toxicology

A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Reproductive and Developmental Toxicity".

Deadline for manuscript submissions: closed (30 September 2025) | Viewed by 18332

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Guest Editor
Department of Physiology and Toxicology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland
Interests: pesticides; endocrine disruptors; environmental toxicology; reproductive disorders; myometrial contractions

Special Issue Information

Dear Colleagues,

Chemical products are indispensable in modern everyday life.  They are a varied and broad group with many different benefits. However, after bioaccumulation in living organisms, they can act as endocrine disruptors and can pose risks to domestic animal or human reproduction.

This Special Issue aims to contribute to novel research on the cellular and molecular mechanisms of endocrine-disrupting chemicals and how they impact reproduction. We encourage the study of currently used chemicals and their metabolites, as well as protection products that are commonly recognized as persistent environmental contaminants and have been banned previously. This can improve their risk assessment, but also potentially aid in finding substances with beneficial effects on reproduction.

Papers may include, but are not limited to, the following topics: the molecular or epigenetic mechanisms behind the toxicity of chemicals; disorders related to the receptivity and further signal transmission of reproductive hormones; in vitro studies; and/or predictive or computational reproductive toxicology approaches.

Authors are invited and welcome to submit original research papers, reviews, short communications, and case reports. 

Dr. Michał Hubert Wróbel
Guest Editor

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Keywords

  • reproductive toxicology
  • endocrine disruptors
  • environmental pollutions
  • parabens
  • pesticides
  • plastic
  • phthalates
  • metals
  • polychlorinated biphenyls
  • polybrominated compounds

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Published Papers (9 papers)

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Research

Jump to: Review

11 pages, 387 KB  
Article
Association of Exposure to Phthalate Metabolites with Antenatal Depression in US Pregnant Women
by Pallavi Dubey, Chinthana Thangavel, Abdelrahman Yousif, Sophie Kim and Sireesha Reddy
Toxics 2025, 13(10), 838; https://doi.org/10.3390/toxics13100838 - 30 Sep 2025
Viewed by 398
Abstract
Antenatal depression affects 10–20% of pregnant women, with notable adverse outcomes for the neonates. Limited studies have indicated a potential link between exposure to phthalate metabolites and depression. The association between phthalate metabolites and depression in pregnant women is unknown. We sought to [...] Read more.
Antenatal depression affects 10–20% of pregnant women, with notable adverse outcomes for the neonates. Limited studies have indicated a potential link between exposure to phthalate metabolites and depression. The association between phthalate metabolites and depression in pregnant women is unknown. We sought to evaluate the association of exposure to phthalate metabolites with depression severity score in US pregnant women. This cross-sectional study used data collected by the National Health and Nutrition Examination Survey during 2005–2018 on pregnant adults who completed urinary profiles that examined 12 common phthalate metabolites. Linear and quantile sum regressions were used to evaluate the association between depressive symptoms (measured by the Patient Health Questionnaire, PHQ-9) and concentrations of phthalate metabolites. A total of 208 women were included in the analysis. These women’s mean (SD) age was 27.42 (5.78) years. We found that all the phthalates were associated with PHQ-9 scores except for mono (carboxyoctyl) and mono-isononyl phthalate. Similar results were observed with the association of high levels of phthalates with mild, moderate, and severe depression (PHQ-9 >4 vs. ≤4). All the phthalate metabolites remained significantly associated with depression scores in the adjusted analysis. Among all considered phthalate metabolites, a combination of MCNP, MBP, MiBP, MnBP, and MEHP contributed to the strongest association with higher depression scores. The relative importance was similar for MCNP (weight = 0.32) and MBP (weight = 0.31), followed by MiBP (weight = 0.12), MnBP (weight = 0.08), MEHP (0.07), and MEP (weight = 0.04) for depression scores. Our findings suggest that pregnant women with high exposure to phthalates are more likely to have higher depressive symptom scores. Full article
(This article belongs to the Special Issue Endocrine-Disrupting Chemicals and Reproductive Toxicology)
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14 pages, 631 KB  
Article
A Comparative Study of the Effect of Commonly Used Pesticides on Cervical Contractions in Pregnant Cows, In Vitro
by Michal Hubert Wrobel
Toxics 2025, 13(9), 793; https://doi.org/10.3390/toxics13090793 - 17 Sep 2025
Viewed by 547
Abstract
Organochlorine insecticides (DDTs), organophosphate insecticides (malathion), carbamate insecticides (carbaryl and thiram), pyrethroid (cypermethrin and fenvalarate) insecticides, and herbicides (glyphosate and atrazine) were selected for this study because they disrupt cervical and myometrial function in the bovine oestrous cycle. However, their potential to affect [...] Read more.
Organochlorine insecticides (DDTs), organophosphate insecticides (malathion), carbamate insecticides (carbaryl and thiram), pyrethroid (cypermethrin and fenvalarate) insecticides, and herbicides (glyphosate and atrazine) were selected for this study because they disrupt cervical and myometrial function in the bovine oestrous cycle. However, their potential to affect reproductive success in cattle during pregnancy has not been directly confirmed. The aim of this study was to determine the effects of the investigated pesticides on cervical contractions in pregnant cows. Cervical strips from cows at 4–6 months of gestation were treated with the eight singular pesticides (used at non-toxic, environmental dose) or oestradiol (E2) under two different conditions (37.5 °C for 24 h and 4 °C for 48 h), which were applied to assess pesticide effects under both physiological and prolonged-exposure settings. The strength of the contractions was then measured. The findings of the study demonstrated that both the carbamates and glyphosate increased the force of cervical strip contractions to a greater extent than cypermethrin. In contrast, fenvalerate was observed to induce a state of cervical relaxation, analogous to the effects of E2, while DDT, malathion and atrazine exerted no effect on cervical motor function during the period of pregnancy under investigation. These preliminary findings indicate a potential impact of pesticides on cervical function during pregnancy, but should be interpreted with caution as they are based on isolated tissue at a single concentration. Further in vivo and dose–response studies are needed to confirm their biological and clinical relevance. Full article
(This article belongs to the Special Issue Endocrine-Disrupting Chemicals and Reproductive Toxicology)
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14 pages, 491 KB  
Article
Analysis of Women’s Knowledge, Health Risk Perceptions, Beliefs and Avoidance Behaviour in Relation to Endocrine-Disrupting Chemicals in Personal Care and Household Products
by Adrianna Trifunovski, Nooshin Khobzi Rotondi, Jennifer Abbass-Dick and Caroline Barakat
Toxics 2025, 13(5), 414; https://doi.org/10.3390/toxics13050414 - 21 May 2025
Cited by 2 | Viewed by 1330
Abstract
Evidence highlights the association between endocrine-disrupting chemicals (EDCs) found in personal care and household products (PCHPs) and adverse reproductive and developmental health outcomes. Women are disproportionately at risk due to frequent use of PCHPs, encountering a variety of different chemicals daily. Despite known [...] Read more.
Evidence highlights the association between endocrine-disrupting chemicals (EDCs) found in personal care and household products (PCHPs) and adverse reproductive and developmental health outcomes. Women are disproportionately at risk due to frequent use of PCHPs, encountering a variety of different chemicals daily. Despite known health risks, existing policies often fail to provide adequate protection, with gaps remaining in understanding women’s knowledge, risk perceptions, and beliefs about EDCSs in PCHP, as well as how these influence avoidance behaviours. This study examines women’s knowledge, health risk perceptions, beliefs, and avoidance behaviors regarding EDCs commonly found in PCHPs, including bisphenol A, lead, parabens, phthalates, perchloroethylene, and triclosan. Guided by the Health Belief Model, a questionnaire was administered to 200 women in the preconception and conception periods in Toronto, Canada. Analyses revealed that lead and parabens were the most recognized EDCs, while triclosan and perchloroethylene were the least known. Greater knowledge of lead, parabens, bisphenol A, and phthalates significantly predicted chemical avoidance in PCHPs. Higher risk perceptions of parabens and phthalates also predicted greater avoidance. Women with higher education and chemical sensitivities were more likely to avoid lead. These findings support the need for targeted education to improve awareness to reduce EDC exposure—especially among women. Full article
(This article belongs to the Special Issue Endocrine-Disrupting Chemicals and Reproductive Toxicology)
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27 pages, 8827 KB  
Article
Modulating Effects of L-Arginine and Tribulus terrestris Extract on Fipronil-Induced Interference in the Male Reproductive System of Rats: Antioxidant Potential, Androgen Receptors, and Nitric Oxide Synthase Interplay
by Doaa H. Elsayed, Ahmed A. Bakhashwain, Eman A. Ahmed, Hatim A. Al-Abbadi, Heba M. A. Abdelrazek, Menna Allah I. El-Menyawy, Wafaa K. Teleb, Noran M. Tawfik, Ibrahim E. Helal and Heba N. Gad EL-Hak
Toxics 2025, 13(5), 371; https://doi.org/10.3390/toxics13050371 - 2 May 2025
Viewed by 3815
Abstract
The protective potentials of Tribulus terrestris (TT) and L-arginine (L-Arg) against reproductive toxicity induced by fipronil (FPN) in male rats were investigated. A total of 36 male rats were allocated into six groups: control, TT, L-Arg, FPN, FPN + TT, and FPN + [...] Read more.
The protective potentials of Tribulus terrestris (TT) and L-arginine (L-Arg) against reproductive toxicity induced by fipronil (FPN) in male rats were investigated. A total of 36 male rats were allocated into six groups: control, TT, L-Arg, FPN, FPN + TT, and FPN + L-Arg groups. The body and sex organ weights, semen criteria, serum testosterone levels, and testicular oxidative stress were determined. Sexual behavior, testicular and penile androgen receptor (AR), penile nitric oxide synthase (NOS), immunohistochemistry of proliferating cell nuclear antigen (PCNA), and histopathology were also assessed. FPN disrupted reproductive health by influencing the expression and activity of NOS and AR, leading to compromised erectile function, sexual dysfunction, and hormonal imbalance. Significant improvements in body weight, reproductive organ weights, the expression of NOS and AR, and testosterone levels were observed in the TT- and L-Arg-treated groups. Behavioral assessments indicated improved sexual performance in the TT- and L-Arg-treated groups. Histopathological studies of the testes and penis tissue, immunohistochemical expression of PCNA in testicular tissues, and biochemical analyses further confirmed the protective effects of TT and L-Arg. Collectively, these findings highlighted the potential of TT and L-Arg in counteracting FPN-induced reproductive impairments. Full article
(This article belongs to the Special Issue Endocrine-Disrupting Chemicals and Reproductive Toxicology)
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12 pages, 1279 KB  
Article
Associations Between Ambient PM2.5 and Thyroid Hormones in Pregnant Persons in Puerto Rico
by Trenton Honda, Trenton D. Henry, Laura Corlin, Kipruto Kirwa, Akram Alshawabkeh, Julia R. Varshavsky, Winston Kennedy, José F. Cordero, Carmen M. Velez Vega, Zaira Y. Rosario Pabon, John D. Meeker and Helen Suh
Toxics 2025, 13(1), 58; https://doi.org/10.3390/toxics13010058 - 15 Jan 2025
Cited by 1 | Viewed by 1854
Abstract
Introduction: This study investigates associations between fine particulate air pollution (PM2.5) exposure and thyroid hormone levels during pregnancy in Puerto Rican individuals, a vulnerable population facing socioeconomic and environmental disparities. Methods: This research draws on data from the PROTECT cohort study [...] Read more.
Introduction: This study investigates associations between fine particulate air pollution (PM2.5) exposure and thyroid hormone levels during pregnancy in Puerto Rican individuals, a vulnerable population facing socioeconomic and environmental disparities. Methods: This research draws on data from the PROTECT cohort study and involves 1040 participants to measure the effect of PM2.5 on developmentally important thyroid hormones (TSH, T3, T4, and FT4). Pollution concentrations were linked to participant locations using EPA air quality data and analyzed across two visits during gestational weeks 16–20 and 24–28. Results: The results suggest that PM2.5 exposure is positively associated with maternal T3, T4, and FT4 levels but not TSH. These effects vary by timing, with T3 showing stronger associations later in pregnancy and T4/FT4 earlier. Nonlinear dose–response relationships were observed, suggesting thresholds for certain hormones. Discussion: These findings support previous studies linking altered thyroid hormones to adverse birth outcomes and highlight the potential role of air pollution in disrupting maternal thyroid function and its implications for fetal development, calling for further research into mechanisms and interventions to mitigate these risks. Full article
(This article belongs to the Special Issue Endocrine-Disrupting Chemicals and Reproductive Toxicology)
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18 pages, 15397 KB  
Article
Perinatal Exposure to Glyphosate or a Commercial Formulation Alters Uterine Mechanistic Pathways Associated with Implantation Failure in Rats
by Ailín Almirón, Virginia Lorenz, Jorgelina Varayoud, Milena Durando and María Mercedes Milesi
Toxics 2024, 12(8), 590; https://doi.org/10.3390/toxics12080590 - 14 Aug 2024
Cited by 1 | Viewed by 1529
Abstract
Perinatal exposure to a glyphosate-based herbicide (GBH) or its active ingredient, glyphosate (Gly), has been demonstrated to increase implantation failure in rats. This study investigates potential mechanisms of action, analyzing uterine preparation towards the receptive state. Pregnant Wistar rats (F0) were treated orally [...] Read more.
Perinatal exposure to a glyphosate-based herbicide (GBH) or its active ingredient, glyphosate (Gly), has been demonstrated to increase implantation failure in rats. This study investigates potential mechanisms of action, analyzing uterine preparation towards the receptive state. Pregnant Wistar rats (F0) were treated orally with GBH or Gly (3.8 and 3.9 mg Gly/kg/day, respectively) from gestational day (GD) 9 until weaning. Adult F1 females became pregnant and uterine samples were collected on GD5 (preimplantation period). Histomorphological uterine parameters were assessed. Immunohistochemistry was applied to evaluate cell proliferation and protein expression of estrogen receptors (ERα and ERβ), cell cycle regulators (PTEN, cyclin G1, p27, and IGF1R-α), and the Wnt5a/β-catenin/FOXA2/Lif pathway. Both GBH and Gly females showed increased stromal proliferation, associated with a high expression of ERs. Dysregulation of PTEN and cyclin G1 was also observed in the Gly group. Reduced gland number was observed in both groups, along with decreased expression of Wnt5a/β-catenin/FOXA2/Lif pathway in the glandular epithelium. Overall, GBH and Gly perinatal exposure disrupted intrinsic uterine pathways involved in endometrial proliferation and glandular function, providing a plausible mechanism for glyphosate-induced implantation failure by compromising uterine receptivity. Similar effects between GBH and Gly suggest the active principle mainly drives the adverse outcomes. Full article
(This article belongs to the Special Issue Endocrine-Disrupting Chemicals and Reproductive Toxicology)
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17 pages, 1910 KB  
Article
Innovative Approach for Human Semen Quality Assessment Based on Volatilomics
by Simonetta Capone, Angiola Forleo, Antonio Vincenzo Radogna, Valentina Longo, Giulia My, Alessandra Genga, Alessandra Ferramosca, Giuseppe Grassi, Flavio Casino, Pietro Siciliano, Tiziana Notari, Sebastiana Pappalardo, Marina Piscopo and Luigi Montano
Toxics 2024, 12(8), 543; https://doi.org/10.3390/toxics12080543 - 27 Jul 2024
Viewed by 2619
Abstract
The volatilome profile of some biofluids (blood, urine, and human semen) identified by Solid-Phase Microextraction–Gas Chromatography/Mass Spectrometry (SPME-GC/MS) and collected from young men living in two high-pollution areas in Italy, i.e., Land of Fires and Valley of Sacco River, have been coupled to [...] Read more.
The volatilome profile of some biofluids (blood, urine, and human semen) identified by Solid-Phase Microextraction–Gas Chromatography/Mass Spectrometry (SPME-GC/MS) and collected from young men living in two high-pollution areas in Italy, i.e., Land of Fires and Valley of Sacco River, have been coupled to sperm parameters obtained by spermiogram analysis to build general multiple regression models. Panels of volatile organic compounds (VOCs) have been selected to optimize the models and used as predictive variables to estimate the different sperm quality parameters (sperm cell concentration, total and progressive motility/immotile cells, total/head/neck/tail morphology anomalies, semen round cell concentration). The results of the multiple linear regression models based on the different subgroups of data joining VOCs from one/two or three biofluids have been compared. Surprisingly, the models based on blood and urine VOCs have allowed an excellent estimate of spermiogram values, paving the way towards a new method of indirect evaluation of semen quality and preventive screening. The significance of VOCs in terms of toxicity and dangerousness was discussed with the support of chemical databases available online. Full article
(This article belongs to the Special Issue Endocrine-Disrupting Chemicals and Reproductive Toxicology)
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18 pages, 2503 KB  
Article
Reproductive and Developmental Effects of Sex-Specific Chronic Exposure to Dietary Arsenic in Zebrafish (Danio rerio)
by Mahesh Rachamalla, Arash Salahinejad, Vladimir Kodzhahinchev and Som Niyogi
Toxics 2024, 12(4), 302; https://doi.org/10.3390/toxics12040302 - 19 Apr 2024
Cited by 9 | Viewed by 3072
Abstract
The present study investigated the reproductive and developmental effects of sex-specific chronic exposure to dietary arsenic in zebrafish. Adult zebrafish (Danio rerio) were exposed to environmentally realistic doses of arsenic via diet [0 (control; no added arsenic), 30 (low), 60 (medium), [...] Read more.
The present study investigated the reproductive and developmental effects of sex-specific chronic exposure to dietary arsenic in zebrafish. Adult zebrafish (Danio rerio) were exposed to environmentally realistic doses of arsenic via diet [0 (control; no added arsenic), 30 (low), 60 (medium), and 100 (high) μg/g dry weight, as arsenite] for 90 days. Following exposure, arsenic-exposed females from each dietary treatment were mated with control males, and similarly, arsenic-exposed males from each dietary treatment were mated with control females. In females, arsenic exposure resulted in a dose-dependent decrease in reproductive performance (fecundity, fertilization success, and hatching success). Moreover, a dose-dependent increase in developmental toxicity (larval deformities and larval mortality) was observed with maternal exposure to arsenic. In contrast, in males, arsenic exposure also induced similar reproductive and developmental toxicity; however, the adverse effects were mainly evident only in the medium and high dietary arsenic treatment groups. We also examined the sex-specific effects of dietary arsenic exposure on the expression of genes that regulate the hypothalamus–pituitary–gonadal–liver (HPG-L) axis in fish. The gene expression results indicated the downregulation of HPG-L axis genes in females irrespective of the arsenic treatment dose; however, the reduced expression of HPG-L axis genes in males was recorded only in the medium and high arsenic treatment groups. These observations suggest that chronic arsenic exposure in either females or males causes reproductive and developmental toxicity in zebrafish. However, these toxic effects are markedly higher in females than in males. Our results also suggest that arsenic can act as an endocrine disruptor and mediate reproductive and developmental toxicity by disrupting the HPG-L axis in zebrafish. Full article
(This article belongs to the Special Issue Endocrine-Disrupting Chemicals and Reproductive Toxicology)
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Review

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21 pages, 1857 KB  
Review
The Ovary as a Target Organ for New Generation Bisphenols Toxicity
by Paulina Głód, Joanna Smoleniec, Weronika Marynowicz, Justyna Gogola-Mruk and Anna Ptak
Toxics 2025, 13(3), 164; https://doi.org/10.3390/toxics13030164 - 26 Feb 2025
Cited by 5 | Viewed by 1932
Abstract
Bisphenols (BPs) are a group of organic compounds used extensively in plastics, coatings, and epoxy resins; they have been of concern recently due to their endocrine-disrupting effects. Among these, bisphenol A (BPA) is the most studied. Regulatory measures, such as the ban on [...] Read more.
Bisphenols (BPs) are a group of organic compounds used extensively in plastics, coatings, and epoxy resins; they have been of concern recently due to their endocrine-disrupting effects. Among these, bisphenol A (BPA) is the most studied. Regulatory measures, such as the ban on BPA use in baby bottles by the European Union and its restricted use in thermal paper, reflect the growing awareness of the health risks of BPA. To mitigate these risks, analogs such as bisphenol S (BPS), bisphenol F (BPF), and others (BPAF, BPAP, BPB, BPP, BPZ) have been developed as alternatives. Despite their intended safety, these analogs have been detected in environmental media, including indoor dust and thermal receipt paper, as well as in human biological samples. Studies report their presence in urine at levels comparable to BPA, with BPS and BPF found in 78% and 55% of samples, respectively. In addition, BPs have been found in human follicular fluid (FF) at concentrations that could exert some paracrine effects on ovarian function and reproductive health. With the increased global production of BPs, occupational exposure and environmental contamination also increase. This review summarizes what is currently known about the effects of BPs on the ovary and the mechanisms by which PBs exert ovarian toxicity, with a particular focus on oogenesis, folliculogenesis, and steroidogenesis. Further, this review emphasizes their influence on reproductive functions and the need for further biosafety evaluations. Full article
(This article belongs to the Special Issue Endocrine-Disrupting Chemicals and Reproductive Toxicology)
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