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

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 21050

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Prof. Dr. Pan Yang

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Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou 510632, China
Interests: environmental exposure and fetal development; environmental exposure and reproductive health
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Endocrine disruption has been an active field of research for over 10 years, although the effects of endocrine disruptors in wildlife have been studied mainly in detail since the 1940s. A large number of chemicals have been identified as endocrine-disrupting chemicals (EDCs) and humans can be exposed to them either due to their occupations or through dietary and environmental exposure (water, soil, and air). Endocrine-disrupting chemicals are compounds that alter the normal functioning of the endocrine system of humans.

It is becoming increasingly difficult to avoid exposure to man-made EDCs and environmental toxicants. Controversy however remains as to whether associations exist, with conflicting findings commonly reported for all major EDC classes. This Special Issue aims to identify robust evidence regarding the effects of environmentally relevant EDC concentrations on adult male and female fertility during the critical periconception period on reproductive hormone concentrations, gamete and embryo characteristics, as well as fetal growth and development in the general population.

This Special Issue seeks to explore environmental EDC exposure and adverse reproductive outcomes. We accept exceptional merit research covering one or more of, but not limited to, the following topics:

Exposure and risk assessment;
Environmental epidemiology;
Compound exposure;
Reproductive health.

Prof. Dr. Pan Yang
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxics is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

reproductive health
exposure assessment
risk assessment
endocrine-disrupting chemicals
fertility and infertility
birth outcome
fetal growth and development

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Published Papers (11 papers)

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Editorial

Jump to: Research

4 pages, 178 KiB

Open AccessEditorial

Editorial for the Special Issue “Environmental Exposure and Reproductive Health”

by Pan Yang

Toxics 2024, 12(3), 216; https://doi.org/10.3390/toxics12030216 - 14 Mar 2024

Viewed by 1082

Abstract

In recent decades, the decline in human fertility has emerged as a significant public health concern, garnering global attention [...] Full article

(This article belongs to the Special Issue Environmental Exposure and Reproductive Health)

Research

Jump to: Editorial

15 pages, 809 KiB

Open AccessArticle

Association between Perfluoroalkyl Substances in Follicular Fluid and Polycystic Ovary Syndrome in Infertile Women

by Sen Li, Guojing Li, Yu Lin, Feng Sun, Liqiang Zheng, Yingying Yu and Hong Xu

Toxics 2024, 12(2), 104; https://doi.org/10.3390/toxics12020104 - 26 Jan 2024

Cited by 2 | Viewed by 1869

Abstract

In recent years, perfluoroalkyl substances (PFASs), a family of fluorinated organic com pounds, have garnered much attention due to their reproductive and developmental toxicity in humans. Polycystic ovary syndrome (PCOS) is a prevalent endocrine disease that affects women of reproductive age and is a significant contributor to female infertility. A previous study suggested that PFASs play a possible role in PCOS. We conducted a clinical study investigating the relationship between PCOS and PFAS in follicular fluid. A total of 73 infertile patients with PCOS and 218 controls were recruited from the International Peace Maternity and Child Health Hospital, affiliated with the Shanghai Jiao Tong University School of Medicine. The concentrations of 12 PFASs in follicular fluid samples and sex hormones in serum were measured. Correlation analysis and multiple linear regression revealed a positive relationship between perfluorooctanoic acid (PFOA) and testosterone (T) concentrations. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each PFAS were estimated using multivariable logistic regression and quantile-based g-computation (QGC). The PFOA concentrations in follicular fluid were correlated with increased odds of PCOS (second vs. first quartile: OR = 3.65, 95% CI: 1.47–9.05, p = 0.005; third vs. first quartile: OR = 2.91, 95% CI: 1.17–7.26, p = 0.022; fourth vs. first quartile: OR = 3.13, 95% CI: 1.21–8.09, p = 0.019; P for trend = 0.032). This association was confirmed with QGC. Mediation analysis suggested that the mediation effect of T in association with PFOA and PCOS was not statistically significant. Our study suggests that PFOA may be a risk factor for PCOS. Full article

(This article belongs to the Special Issue Environmental Exposure and Reproductive Health)

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14 pages, 3880 KiB

Open AccessArticle

N-Acetyl-L-Cysteine Ameliorates BPAF-Induced Porcine Sertoli Cell Apoptosis and Cell Cycle Arrest via Inhibiting the ROS Level

by Yue Feng, Junjing Wu, Runyu Lei, Yu Zhang, Mu Qiao, Jiawei Zhou, Zhong Xu, Zipeng Li, Hua Sun, Xianwen Peng and Shuqi Mei

Toxics 2023, 11(11), 923; https://doi.org/10.3390/toxics11110923 - 11 Nov 2023

Cited by 3 | Viewed by 1655

Abstract

Bisphenol AF (BPAF) is a newly identified contaminant in the environment that has been linked to impairment of the male reproductive system. However, only a few studies have systematically studied the mechanisms underlying BPAF-induced toxicity in testicular Sertoli cells. Hence, this study primarily aims to explore the toxic mechanism of BPAF on the porcine Sertoli cell line (ST cells). The effects of various concentrations of BPAF on ST cell viability and cytotoxicity were evaluated using the Counting Kit-8 (CCK-8) assay. The results demonstrated that exposure to a high concentration of BPAF (above 50 μM) significantly inhibited ST cell viability due to marked cytotoxicity. Flow cytometry analysis further confirmed that BPAF facilitated apoptosis and induced cell cycle arrest in the G2/M phase. Moreover, BPAF exposure upregulated the expression of pro-apoptotic markers BAD and BAX while downregulating anti-apoptotic and cell proliferation markers BCL-2, PCNA, CDK2, and CDK4. BPAF exposure also resulted in elevated intracellular levels of reactive oxygen species (ROS) and malondialdehyde (MDA), alongside reduced activities of the antioxidants glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Furthermore, the ROS scavenger N-acetyl-L-cysteine (NAC) effectively blocked BPAF-triggered apoptosis and cell cycle arrest. Therefore, this study suggests that BPAF induces apoptosis and cell cycle arrest in ST cells by activating ROS-mediated pathways. These findings enhance our understanding of BPAF’s role in male reproductive toxicity and provide a foundation for future toxicological assessments. Full article

(This article belongs to the Special Issue Environmental Exposure and Reproductive Health)

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12 pages, 492 KiB

Open AccessArticle

Investigation of the Relationship between Spontaneous Abortion, Serum Pesticides, and Polychlorinated Biphenyl Levels

by Jale Akgöl and Mine Kanat Pektaş

Toxics 2023, 11(11), 884; https://doi.org/10.3390/toxics11110884 - 27 Oct 2023

Viewed by 1629

Abstract

Occupational and environmental chemical exposure have been associated with adverse reproductive consequences. This study investigates the relationship between spontaneous abortion and blood pesticide and polychlorinated biphenyl (PCB) levels. A survey was conducted, and blood samples were collected from 200 patients, consisting of 100 cases with spontaneous abortion and 100 cases with normal deliveries. A total of 150 different pesticides, including organophosphates, organochlorines, carbamates, and pyrethroids, were screened in the collected blood samples and analyzed quantitatively using Tandem mass spectrometry—specifically in combination with liquid chromatography and gas chromatography–tandem mass spectrometry methods. Eight types of PCBs were analyzed with the gas chromatography-tandem mass spectrometry method. The groups were compared based on these analyses. The mean age of the participants was 28.09 ± 4.94 years. In 59% of the spontaneous abortion group, 5.05 ± 1.97 chemicals were detected in different amounts. (p < 0.05). Analysis of the samples identified the presence of β-Hexachlorocyclohexane (β-HCH), delta-hexachlorocyclohexane (δ HCH), Hexachlorobenzene (HCB), Pentachlorobiphenyl-28 (PCB-28), Pentachlorobiphenyl-52 (PCB-52), o,p′-Dichlorodiphenyldichloroethylene (o,p′-DDE), p,p′-Dichlorodiphenyldichloroethylene (p,p’DDE), o,p′-Dichlorodiphenyldichloroethane (o,p′-DDD), p,p′-Dichlorodiphenyldichloroethane (p,p′-DDD), Pentachlorobiphenyl-118 (PCB-118), Pentachlorobiphenyl-101 (PCB-101), Pentachlorobiphenyl-153 (PCB-153), Pentachlorobiphenyl-138 (PCB-138), Pentachlorobiphenyl-202 (PCB-202), Pentachlorobiphenyl-180 (PCB-180) as well as Fibronil, Buprimate, Acetoclor, Acemiprid, Pentimanthalin, and Triflokystrobin. The spontaneous abortion group had significantly higher exposure to PCB-101, PCB-52, PCB-138, and δ-HCH (p < 0.05). Women included in the study had high pesticide and PCB exposure rates. Many of the blood samples contained multiple pesticides with endocrine-disrupting effects. Higher exposure to organochlorine compounds in the serum was identified in the group with spontaneous abortions. Full article

(This article belongs to the Special Issue Environmental Exposure and Reproductive Health)

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14 pages, 1767 KiB

Open AccessArticle

Single and Joint Associations of Polycyclic Aromatic Hydrocarbon Exposure with Liver Function during Early Pregnancy

by Mi Dai, Lei Luo, Caiyan Xie, Zhongbao Chen, Mingzhe Zhang, Yan Xie, Xuejun Shang, Xubo Shen, Kunming Tian and Yuanzhong Zhou

Toxics 2023, 11(10), 863; https://doi.org/10.3390/toxics11100863 - 16 Oct 2023

Cited by 1 | Viewed by 1538

Abstract

The individual and combined associations of polycyclic aromatic hydrocarbons (PAHs) metabolites on liver function during pregnancy are still lacking. We aimed to explore the connection between urinary PAH metabolites and liver function in early pregnant women in southwest China based on the Zunyi birth cohort. Ten urinary PAH metabolites and five liver function parameters during early pregnancy were measured. The associations of single PAHs with parameters of liver function were assessed using multiple linear regression. A Bayesian kernel machine regression (BKMR) model was used to evaluate the joint associations of the PAH mixture with outcomes. We found that each 1% increment of urinary 2-hydroxyphenanthrene (2-OH-PHE) was associated with 3.36% (95% CI: 0.40%, 6.40%) higher alanine aminotransferase (ALT) and 2.22% (95% CI: 0.80%, 3.67%) higher aspartate aminotransferase (AST). Each 1% increment in 1-hydroxy-phenanthrene (1-OH-PHE) was significantly associated with 7.04% (95% CI: 1.61%, 12.75%) increased total bile acid (TBA). Additionally, there was a significant positive linear trend between 2-OH-PHE and AST and 1-OH-PHE and TBA. BKMR also showed a significant positive association of PAH mixture with AST. Our results indicate that PAH metabolites were associated with increased parameters of liver function among early pregnant women. Early pregnant women should pay more attention to the adverse relationships between PAHs and liver function parameters to prevent environment-related adverse perinatal outcomes. Full article

(This article belongs to the Special Issue Environmental Exposure and Reproductive Health)

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15 pages, 1644 KiB

Open AccessArticle

Exposure of Reproductive-Aged Women to Multiple Metals and Its Associations with Unexplained Recurrent Miscarriage

by Yingying Zhang, Xi Yan, Jianhua Tan, Jifan Tan, Chunsheng Liu, Pan Yang, Yanping Xian and Qiong Wang

Toxics 2023, 11(10), 830; https://doi.org/10.3390/toxics11100830 - 30 Sep 2023

Cited by 2 | Viewed by 1990

Abstract

Exposure to heavy metals exerts toxic effects on female reproduction and embryo development. This study examined the exposure of patients with unexplained recurrent miscarriage (uRM) to multiple metals and the correlations among exposures to different metals. A total of 275 participants were enrolled, including 43 healthy women without previous miscarriage (the control group) and 232 uRM women (the case group); among these uRM women, 159 had two miscarriages (2M), 42 had three miscarriages (3M) and 31 had four or more miscarriages (≥4M). A total of 22 elements were measured in serum samples via inductively coupled plasma–mass spectrometry. The levels of calcium (104.37 mg/L vs. 92.65/93.02/92.61/92.47 mg/L) and selenium (131.85 µg/L vs. 117.80/118.04/115.88/124.35 µg/L) were higher in the controls than in the total uRM group and the 2M, 3M and ≥4M subgroups. The level of vanadium was significantly lower in the controls than in the total uRM group (0.15 µg/L vs. 0.23 µg/L), and the level of lead was lower in the controls than that in the total uRM group and the 2M, 3M and ≥4M subgroups (0.01 µg/L vs. 0.28/0.18/0.63/0.34 µg/L). After adjusting for age, body mass index and education level, calcium and selenium exposure were consistently negatively associated with miscarriage, while lead exposure was positively associated with miscarriage. In addition, the correlations among exposures to different metals slightly differed between the control and uRM groups. Therefore, changes in some metal elements in the blood might be related to the risk of uRM. Full article

(This article belongs to the Special Issue Environmental Exposure and Reproductive Health)

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16 pages, 3738 KiB

Open AccessArticle

Co-Exposure of Polycyclic Aromatic Hydrocarbons and Phthalates with Blood Cell-Based Inflammation in Early Pregnant Women

by Yunxiao Yang, Ting Wang, Lei Luo, Qian He, Fangfei Guo, Zhongbao Chen, Yijun Liu, Xingyan Liu, Yan Xie, Xuejun Shang, Xubo Shen, Yuanzhong Zhou and Kunming Tian

Toxics 2023, 11(10), 810; https://doi.org/10.3390/toxics11100810 - 25 Sep 2023

Cited by 4 | Viewed by 1705

Abstract

Cumulative evidence has demonstrated that exposure to polycyclic aromatic hydrocarbons (PAHs) or phthalates (PAEs) contributes to a variety of adverse health effects. However, the association of PAHs and PAEs co-exposure with blood cell-based inflammatory indicators during early pregnancy is still unclear. We aimed to investigate the single and mixed associations of exposure to PAHs and PAEs with blood cell-based inflammatory indicators among early pregnant women. A total of 318 early pregnant women were included in this study. General linear regressions were used to estimate the relationships of individual OH-PAHs and mPAEs with blood cell-based inflammatory indicators. The key pollutants were selected by an adapted least absolute shrinkage and selection operator (LASSO) penalized regression model and wasemployed to build the Bayesian kernel machine regression (BKMR) and quantile g-computation (Q-g) models, which can assess the joint association of OH-PAHs and mPAEs with blood cell-based inflammatory indicators. General linear regression indicated that each 1% increase in MOP was associated with a 4.92% (95% CI: 2.12%, 7.68%), 3.25% (95% CI: 0.50%, 6.18%), 5.87% (95% CI: 2.22%, 9.64%), and 6.50% (95% CI: 3.46%, 9.64%) increase in WBC, lymphocytes, neutrophils, and monocytes, respectively. BKMR and Q-g analysis showed that the mixture of OH-PAHs and mPAEs was linked with increased levels of white blood cells (WBC), neutrophils, monocytes, and lymphocytes, and MOP was identified as the dominant contributor. OH-PAHs and mPAEs co-exposure in early pregnancy was associated with elevated blood cell-based inflammatory indicators reactions. More attention should be paid to the inflammation induced by environmental pollution for perinatal women, especially early pregnant women. Full article

(This article belongs to the Special Issue Environmental Exposure and Reproductive Health)

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19 pages, 10080 KiB

Open AccessEditor’s ChoiceArticle

Impact of Perinatal Coexposure to Chlorpyrifos and a High-Fat Diet on Kisspeptin and GnRHR Presence and Reproductive Organs

by Marwa Lahimer, Narimane Djekkoun, Sophian Tricotteaux-Zarqaoui, Aurélie Corona, Isabelle Lafosse, Habib Ben Ali, Mounir Ajina, Véronique Bach, Moncef Benkhalifa and Hafida Khorsi-Cauet

Toxics 2023, 11(9), 789; https://doi.org/10.3390/toxics11090789 - 19 Sep 2023

Cited by 1 | Viewed by 1591

Abstract

Emerging evidence has indicated the involvement of extrahypothalamic Kisspeptin and GnRHR in reproductive function. In this study, we evaluate if maternal exposure to the pesticide chlorpyrifos (CPF) and/or a high-fat diet (HFD) has an impact on the expression of Kisspeptin and GnRHR in the reproductive organs of rats’ offspring. A total of 16 pregnant rats are divided into four groups: a control group (n = 4), CPF group (4 rats exposed daily to 1/mg/kg/day), HFD group (4 rats randomly fed a 5.25 kcal/g HFD), and coexposed group (4 rats exposed to CPF and HDF). At postnatal development postnatal day (PND) 60, male and female offspring were sacrificed. The reproductive organs (ovary and testis) were removed, and histological and immunohistological analysis and in silico quantification (TissueGnostics software 6.0.1.102, TissueFAXS, HistoQuest) were applied to investigate the impact of different treatments on Kisspeptin and GnRHR expression in reproductive organs. The main outcomes of the study showed a significant decrease in rat offspring’s body weight in the CPF group from PND30 and PND60 (p < 0.05 and p < 0.01, respectively). Histological analysis showed a significant increase in the atretic follicle and abnormal testis structure with germ cell desquamation in the CPF-exposed group. The immunodetection quantification of protein shows a significant decrease in GnRHR and Kisspeptin in the HFD and CPF exposed groups, respectively, in testis rat offspring. Perinatal exposure to CPF and HFD exposure affect the reproduction function of rat offspring. Full article

(This article belongs to the Special Issue Environmental Exposure and Reproductive Health)

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11 pages, 3888 KiB

Open AccessArticle

Incidence of Morphological Defects in Sperm of Mice Exposed to Hospital Effluent

by Priyanka Mathur, Kusum Rani, Pradeep Bhatnagar and Swaran Jeet Singh Flora

Toxics 2023, 11(5), 418; https://doi.org/10.3390/toxics11050418 - 29 Apr 2023

Cited by 1 | Viewed by 1887

Abstract

Hospital effluents are loaded with drugs, radioactive elements, pathogens, etc. Effluents from treatment plants at source sites may get mixed up with potable water, leading to numerous detrimental/toxic effects. In this study, efforts were made to investigate the toxic effects of one such effluent from a local hospital on the reproductive characteristics of mice when orally administered daily for 60 consecutive days. We primarily focused on the changes in the morphology of the sperm and its geometric morphometrics, i.e., sperm head length and width, area, and perimeter, measured using ImageJ software. The incidence of sperm defects was recorded, and variations in the morphometrics were analyzed by one-way ANOVA using Tukey’s post hoc test. A physico-chemical characterization of the water samples was also performed to assess the basic water quality. In summary, the study revealed the critical role of treated water in inducing different abnormalities in sperm, such as the absence of a head, bent necks, abnormal neck attachment, highly coiled tails, and missing tails. Significant differences (p < 0.01 **, p < 0.001 ***) in the morphometrics of spermatozoa with banana heads, hammer heads, missing heads, pin heads, and missing hooks were noted compared to corresponding controls. It could thus be concluded that treated hospital effluent is still inadequately clean and contains significant amounts of toxicants that might be detrimental to sperm quality. Full article

(This article belongs to the Special Issue Environmental Exposure and Reproductive Health)

17 pages, 5342 KiB

Open AccessEditor’s ChoiceArticle

Imidacloprid and Its Bioactive Metabolite, Desnitro-Imidacloprid, Differentially Affect Ovarian Antral Follicle Growth, Morphology, and Hormone Synthesis In Vitro

by Vasiliki E. Mourikes, Ramsés Santacruz Márquez, Ashley Deviney, Alison M. Neff, Mary J. Laws and Jodi A. Flaws

Toxics 2023, 11(4), 349; https://doi.org/10.3390/toxics11040349 - 7 Apr 2023

Cited by 12 | Viewed by 2245

Abstract

Imidacloprid is a neonicotinoid pesticide used in large-scale agricultural systems, home gardens, and veterinary pharmaceuticals. Imidacloprid is a small molecule that is more water-soluble than other insecticides, increasing the likelihood of large-scale environmental accumulation and chronic exposure of non-targeted species. Imidacloprid can be converted to the bioactive metabolite desnitro-imidacloprid in the environment and body. Little is known about the mechanisms by which imidacloprid and desnitro-imidacloprid induce ovarian toxicity. Thus, we tested the hypothesis that imidacloprid and desnitro-imidacloprid differentially affect antral follicle growth and steroidogenesis in vitro. Antral follicles were dissected from the ovaries of CD-1 mice and cultured in media containing vehicle control or 0.2 µg/mL–200 µg/mL of imidacloprid or desnitro-imidacloprid for 96 h. Follicle morphology was monitored, and follicle size was measured every 24 h. At the end of the culture periods, media were used to quantify follicular hormone levels, and follicles were used for gene expression analysis of steroidogenic regulators, hormone receptors, and apoptotic factors. Imidacloprid did not affect follicle growth or morphology compared to the control. Desnitro-imidacloprid inhibited follicle growth and caused follicles to rupture in culture compared to the control. Imidacloprid increased progesterone, whereas desnitro-imidacloprid decreased testosterone and progesterone compared to the control. Desnitro-imidacloprid also changed estradiol compared to the control. At 48 h, IMI decreased the expression of Star, Cyp17a1, Hsd17b1, Cyp19a1, and Esr2 and increased the expression of Cyp11a1, Cyp19a1, Bax, and Bcl2 compared to the control. IMI also changed the expression of Esr1 compared to the control. At 48 h, DNI decreased the expression of Cyp11a1, Cyp17a1, Hsd3b1, Cyp19a1, and Esr1 and increased the expression of Cyp11a1, Hsd3b1, and Bax compared to the control. At 72 h of culture, IMI significantly decreased the expression of Cyp19a1 and increased the expression of Star and Hsd17b1 compared to the control. At 72 h, DNI significantly decreased the expression of Cyp11a1, Cyp17a1, Hsd3b1, and Bax and increased the expression of Esr1 and Esr2. At 96 h, IMI decreased the expression of Hsd3b1, Cyp19a1, Esr1, Bax, and Bcl2 compared to the control. At 96 h, DNI decreased the expression of Cyp17a1, Bax, and Bcl2 and increased the expression of Cyp11a1, Hsd3b1, and Bax compared to the control. Together, these data suggest mouse antral follicles are targets of neonicotinoid toxicity, and the mechanisms of toxicity differ between parent compounds and metabolites. Full article

(This article belongs to the Special Issue Environmental Exposure and Reproductive Health)

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13 pages, 810 KiB

Open AccessArticle

Reproductive Effects of S. boulardii on Sub-Chronic Acetamiprid and Imidacloprid Toxicity in Male Rats

by Çiğdem Sevim, Erol Akpınar, Emrah Hicazi Aksu, Ali Doğan Ömür, Serkan Yıldırım, Mehtap Kara, İsmail Bolat, Aristides Tsatsakis, Robin Mesnage, Kirill S. Golokhvast, Sevgi Karabulut Uzunçakmak and Rabia Nilüfer Ersoylu

Toxics 2023, 11(2), 170; https://doi.org/10.3390/toxics11020170 - 12 Feb 2023

Cited by 6 | Viewed by 2697

Abstract

The potential health-promoting effects of probiotics against intoxication by pesticides is a topic of increasing commercial interest with limited scientific evidence. In this study, we aimed to investigate the positive effects of probiotic Saccharomyces boulardii on the male reproductive system under low dose neonicotinoid pesticide exposure conditions. We observed that acetamiprid and imidacloprid caused a degeneration and necrosis of the spermatocytes in the tubular wall, a severe edema of the intertubular region and a hyperemia. This was concomittant to increased levels of 8-hydroxy-2′-deoxyguanosine reflecting oxidative stress, and an increase in caspase 3 expression, reflecting apoptosis. According to our results, Saccharomyces boulardii supplementation mitigates these toxic effects. Further in vivo and clinical studies are needed to clarify the molecular mechanisms of protection. Altogether, our study reinforces the burden of evidence from emerging studies linking the composition of the gut microbiome to the function of the reproductive system. Full article

(This article belongs to the Special Issue Environmental Exposure and Reproductive Health)

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