August 2023
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32 Reads
[This corrects the article DOI: 10.3389/fphys.2021.807685.].
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August 2023
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32 Reads
[This corrects the article DOI: 10.3389/fphys.2021.807685.].
February 2023
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43 Reads
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3 Citations
Marine Drugs
New bronchopulmonary dysplasia (BPD) is a neonatal disease that is theorized to begin in utero and manifests as reduced alveolarization due to inflammation of the lung. Risk factors for new BPD in human infants include intrauterine growth restriction (IUGR), premature birth (PTB) and formula feeding. Using a mouse model, our group recently reported that a paternal history of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure increased his offspring’s risk of IUGR, PTB, and new BPD. Additionally, formula supplementation of these neonates worsened the severity of pulmonary disease. In a separate study, we reported that a paternal preconception fish oil diet prevented TCDD-driven IUGR and PTB. Not surprisingly, eliminating these two major risk factors for new BPD also significantly reduced development of neonatal lung disease. However, this prior study did not examine the potential mechanism for fish oil’s protective effect. Herein, we sought to determine whether a paternal preconception fish oil diet attenuated toxicant-associated lung inflammation, which is an important contributor to the pathogenesis of new BPD. Compared to offspring of standard diet TCDD-exposed males, offspring of TCDD-exposed males provided a fish oil diet prior to conception exhibited a significant reduction in pulmonary expression of multiple pro-inflammatory mediators (Tlr4, Cxcr2, Il-1 alpha). Additionally, neonatal lungs of pups born to fish oil treated fathers exhibited minimal hemorrhaging or edema. Currently, prevention of BPD is largely focused on maternal strategies to improve health (e.g., smoking cessation) or reduce risk of PTB (e.g., progesterone supplementation). Our studies in mice support a role for also targeting paternal factors to improve pregnancy outcomes and child health.
June 2022
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36 Reads
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6 Citations
Marine Drugs
Epidemiology and animal studies suggest that a paternal history of toxicant exposure contributes to the developmental origins of health and disease. Using a mouse model, our laboratory previously reported that a paternal history of in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased his offspring’s risk of developing necrotizing enterocolitis (NEC). Additionally, our group and others have found that formula supplementation also increases the risk of NEC in both humans and mice. Our murine studies revealed that intervening with a paternal fish oil diet preconception eliminated the TCDD-associated outcomes that are risk factors for NEC (e.g., intrauterine growth restriction, delayed postnatal growth, and preterm birth). However, the efficacy of a paternal fish oil diet in eliminating the risk of disease development in his offspring was not investigated. Herein, reproductive-age male mice exposed to TCDD in utero were weaned to a standard or fish oil diet for one full cycle of spermatogenesis, then mated to age-matched unexposed females. Their offspring were randomized to a strict maternal milk diet or a supplemental formula diet from postnatal days 7–10. Offspring colon contents and intestines were collected to determine the onset of gut dysbiosis and NEC. We found that a paternal fish oil diet preconception reduced his offspring’s risk of toxicant-driven NEC, which was associated with a decrease in the relative abundance of the Firmicutes phylum, but an increase in the relative abundance of the Negativicutes class.
January 2022
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200 Reads
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30 Citations
Women with endometriosis, the growth of endometrial glands and stroma outside the uterus, commonly also exhibit adenomyosis, the growth of endometrial tissues within the uterine muscle. Each disease is associated with functional alterations in the eutopic endometrium frequently leading to pain, reduced fertility, and an increased risk of adverse pregnancy outcomes. Although the precise etiology of either disease is poorly understood, evidence suggests that the presence of endometriosis may be a contributing factor to the subsequent development of adenomyosis as a consequence of an altered, systemic inflammatory response. Herein, we will discuss the potential role of exposure to environmental toxicants with endocrine disrupting capabilities in the pathogenesis of both endometriosis and adenomyosis. Numerous epidemiology and experimental studies support a role for environmental endocrine disrupting chemicals (EDCs) in the development of endometriosis; however, only a few studies have examined the potential relationship between toxicant exposures and the risk of adenomyosis. Nevertheless, since women with endometriosis are also frequently found to have adenomyosis, discussion of EDC exposure and development of each of these diseases is relevant. We will discuss the potential mechanisms by which EDCs may act to promote the co-development of endometriosis and adenomyosis. Understanding the disease-promoting mechanisms of environmental toxicants related to endometriosis and adenomyosis is paramount to designing more effective treatment(s) and preventative strategies.
December 2021
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50 Reads
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4 Citations
Toxics
New bronchopulmonary dysplasia is a developmental lung disease associated with placental dysfunction and impaired alveolarization. Risk factors for new BPD include prematurity, delayed postnatal growth, the dysregulation of epithelial-to-mesenchymal transition (EMT), and parental exposure to toxicants. Our group previously reported that a history of paternal toxicant exposure increased the risk of prematurity and low birth weight in offspring. A history of paternal toxicant exposure also increased the offspring’s risk of new BPD and disease severity was increased in offspring who additionally received a supplemental formula diet, which has also been linked to poor lung development. Risk factors associated with new BPD are well-defined, but it is unclear whether the disease can be prevented. Herein, we assessed whether a paternal fish oil diet could attenuate the development of new BPD in the offspring of toxicant exposed mice, with and without neonatal formula feeding. We investigated the impact of a paternal fish oil diet preconception because we previously reported that this intervention reduces the risk of TCDD associated placental dysfunction, prematurity, and low birth weight. We found that a paternal fish oil diet significantly reduced the risk of new BPD in neonatal mice with a history of paternal toxicant exposure regardless of neonatal diet. Furthermore, our evidence suggests that the protective effects of a paternal fish oil diet are mediated in part by the modulation of small molecules involved in EMT.
... A growing body of research from rodent models is shedding light on potential mechanisms through which paternal factors including dietary predilections [14,31], exposure to environmental stressors like toxicants [32], and epigenetic modifications within spermatozoa [33] can have longterm effects on offspring health. For instance, several studies using mainly rodent animal-based models have identified links between paternal diet, obesity and low sperm quality and increased risks of cardio-metabolic disorders (e.g., obesity and type 2 diabetes) in offspring [34][35][36][37]. ...
February 2023
Marine Drugs
... Another murine study showed that a paternal diet containing high fish oil before conception reduced the incidence of necrotizing enterocolitis in the offspring [47]. According to the followup study, male mice fed fish oil for one spermatogenic cycle prior to mating showed a decrease in pulmonary inflammation and respiratory pro-inflammatory cytokine expression in the pups [32]. ...
June 2022
Marine Drugs
... Moreover, a recent systematic review of 50 epidemiological studies highlighted positive associations between endometriosis and several environmental contaminants, including polychlorinated biphenyls, dioxins, phthalates, organochlorines, and bisphenol A 175 . These substances may disrupt tissue homeostasis through various mechanisms, such as acting as endocrine disruptors, modulating immune function, inducing oxidative stress and perturbing epigenetic processes [176][177][178] . Consequently, such disruptions can perturb endometrial cell functions and pathways that regulate cell proliferation, differentiation, and decidualization 179,180 , leading to perturbations on the cellular and/or organ level. ...
January 2022
... Since IUGR and PTB are well-known risk factors for new BPD, our group recently assessed the incidence of this disease in offspring of TCDD-exposed males (F2 TCDD mice). We demonstrated that new BPD was common in F2 TCDD pups, and that formula supplementation of these neonates heightened the severity of disease [9,10]. ...
December 2021
Toxics