The potential reproductive effects of exposure of domestic ruminants to endocrine disrupting compounds

AbstractChemical compounds that mimic or block some of the actions of the steroid hormone oestradiol, have created public concern primarily because of potential adverse reproductive effects in wildlife and humans. Many studies, in vivo and in vitro, have revealed abnormal reproductive function following exposure to these compounds. The number of chemicals known to have the potential to modulate endocrine functions is increasing. In contrast to humans and wildlife, the potential reproductive effects of exposure of domestic animals to endocrine disrupting compounds (EDC) have been studied little. The aim of this overview is to evaluate the possible contribution of EDC to reproductive failure in domestic ruminants.Sources and classes of EDC are discussed as well as their structure and the modes of hormone disruption. Endocrine disrupting agents may interfere with the reproductive processes of both males and females at several points of the reproductive cycle and through a range of physiological mechanisms. Extrapolating from the results obtained with laboratory animals, the mechanisms whereby infertility in domestic ruminants might be expressed by exposure to EDC through contaminated food and drinking water are addressed.A preliminary risk assessment is included and it is concluded that under certain circumstances there may be a significantly enhanced intake of oestrogenic hormones and EDC through sewage-contaminated water or soil-contaminated herbage. The physiological consequences for domestic ruminants of EDC ingestion, at the rates estimated, are largely unknown. However, the levels of exposure to oestrogenic hormones and phthalates in grazing ruminants are such that when studying fertility problems in high-yielding dairy cattle the impacts of exposure to endocrine disruptors via the food and drinking water cannot be neglected.

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In vitro-to-in vivo extrapolation (IVIVE) by PBTK modeling for animal-free risk assessment approaches of potential endocrine-disrupting compounds

Archives of Toxicology ◽

10.1007/s00204-018-2372-z ◽

2018 ◽

Vol 93 (2) ◽

pp. 401-416 ◽

Cited By ~ 17

Author(s):

Eric Fabian ◽

Caroline Gomes ◽

Barbara Birk ◽

Tabitha Williford ◽

Tzutzuy Ramirez Hernandez ◽

...

Keyword(s):

Risk Assessment ◽

Endocrine Disrupting Compounds ◽

Endocrine Disrupting ◽

In Vivo Extrapolation

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Balancing the budget of environmental estrogen exposure: the contribution of recycled water

Water Science & Technology ◽

10.2166/wst.2009.398 ◽

2009 ◽

Vol 60 (4) ◽

pp. 1003-1012 ◽

Cited By ~ 8

Author(s):

Frederic D. L. Leusch ◽

Michael R. Moore ◽

Heather F. Chapman

Keyword(s):

Endocrine Disrupting Compounds ◽

Dietary Intakes ◽

Recycled Water ◽

Environmental Media ◽

Estrogen Exposure ◽

Treated Sewage ◽

Endocrine Disrupting ◽

17Β Estradiol

Estrogenic endocrine disrupting compounds (e-EDCs) are present in treated sewage and there is concern about estrogenicity of potable recycled water. However e-EDCs are also present in other environmental media and intake from water needs to be considered in relation to these other sources. The concentrations of 13 e-EDCs in foodstuffs and drinking water are reviewed, their predicted concentrations in recycled water are estimated, and the daily estrogenic intake as 17β-estradiol equivalent (EEq) based on both in vitro and in vivo potencies is calculated as 1.39 and 9.65 μg EEq/d, respectively. Dietary intake accounts for more than 99.8% of that total, and more than 84.2% is due to phytosterols. Drinking 2 L of recycled water per day is expected to add 0.001 to 0.016 μg EEq/d based on in vitro and in vivo potencies, respectively. Exposure to e-EDCs in recycled water is therefore likely to be insignificant compared to current dietary intakes.

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Neurotoxicity of Pesticides: The Roadmap for the Cubic Mode of Action

Current Medicinal Chemistry ◽

10.2174/0929867326666190704142354 ◽

2020 ◽

Vol 27 (1) ◽

pp. 54-77 ◽

Cited By ~ 2

Author(s):

Bogdan Bumbăcilă ◽

Mihai V. Putz

Keyword(s):

Biological Activity ◽

Wiener Index ◽

Laboratory Animals ◽

Covalent Bonds ◽

Organophosphate Compounds ◽

Sar Studies ◽

Structure Activity ◽

Cubic Structure

Pesticides are used today on a planetary-wide scale. The rising need for substances with this biological activity due to an increasing consumption of agricultural and animal products and to the development of urban areas makes the chemical industry to constantly investigate new molecules or to improve the physicochemical characteristics, increase the biological activities and improve the toxicity profiles of the already known ones. Molecular databases are increasingly accessible for in vitro and in vivo bioavailability studies. In this context, structure-activity studies, by their in silico - in cerebro methods, are used to precede in vitro and in vivo studies in plants and experimental animals because they can indicate trends by statistical methods or biological activity models expressed as mathematical equations or graphical correlations, so a direction of study can be developed or another can be abandoned, saving financial resources, time and laboratory animals. Following this line of research the present paper reviews the Structure-Activity Relationship (SAR) studies and proposes a correlation between a topological connectivity index and the biological activity or toxicity made as a result of a study performed on 11 molecules of organophosphate compounds, randomly chosen, with a basic structure including a Phosphorus atom double bounded to an Oxygen atom or to a Sulfur one and having three other simple covalent bonds with two alkoxy (-methoxy or -ethoxy) groups and to another functional group different from the alkoxy groups. The molecules were packed on a cubic structure consisting of three adjacent cubes, respecting a principle of topological efficiency, that of occupying a minimal space in that cubic structure, a method that was called the Clef Method. The central topological index selected for correlation was the Wiener index, since it was possible this way to discuss different adjacencies between the nodes in the graphs corresponding to the organophosphate compounds molecules packed on the cubic structure; accordingly, "three dimensional" variants of these connectivity indices could be considered and further used for studying the qualitative-quantitative relationships for the specific molecule-enzyme interaction complexes, including correlation between the Wiener weights (nodal specific contributions to the total Wiener index of the molecular graph) and the biochemical reactivity of some of the atoms. Finally, when passing from SAR to Q(uantitative)-SAR studies, especially by the present advanced method of the cubic molecule (Clef Method) and its good assessment of the (neuro)toxicity of the studied molecules and of their inhibitory effect on the target enzyme - acetylcholinesterase, it can be seen that a predictability of the toxicity and activity of different analogue compounds can be ensured, facilitating the in vivo experiments or improving the usage of pesticides.

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Legislation against endocrine-disrupting compounds in drinking water: essential but not enough to ensure water safety

Environmental Science and Pollution Research ◽

10.1007/s11356-021-12901-1 ◽

2021 ◽

Author(s):

Ze-hua Liu ◽

Zhi Dang ◽

Yu Liu

Keyword(s):

Drinking Water ◽

Endocrine Disrupting Compounds ◽

Water Safety ◽

Endocrine Disrupting

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Graphene and Reproduction: A Love-Hate Relationship

Nanomaterials ◽

10.3390/nano11020547 ◽

2021 ◽

Vol 11 (2) ◽

pp. 547

Author(s):

Marina Ramal-Sanchez ◽

Antonella Fontana ◽

Luca Valbonetti ◽

Alessandra Ordinelli ◽

Nicola Bernabò ◽

...

Keyword(s):

Graphene Oxide ◽

Reproductive Function ◽

Scientometric Analysis ◽

Potential Toxicity ◽

Good Tool ◽

Vitro Fertilization ◽

Number Of Publications ◽

The Individual

Since its discovery, graphene and its multiple derivatives have been extensively used in many fields and with different applications, even in biomedicine. Numerous efforts have been made to elucidate the potential toxicity derived from their use, giving rise to an adequate number of publications with varied results. On this basis, the study of the reproductive function constitutes a good tool to evaluate not only the toxic effects derived from the use of these materials directly on the individual, but also the potential toxicity passed on to the offspring. By providing a detailed scientometric analysis, the present review provides an updated overview gathering all the research studies focused on the use of graphene and graphene-based materials in the reproductive field, highlighting the consequences and effects reported to date from experiments performed in vivo and in vitro and in different animal species (from Archea to mammals). Special attention is given to the oxidized form of graphene, graphene oxide, which has been recently investigated for its ability to increase the in vitro fertilization outcomes. Thus, the potential use of graphene oxide against infertility is hypothesized here, probably by engineering the spermatozoa and thus manipulating them in a safer and more efficient way.

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Scientific issues associated with the validation of in vitro and in vivo methods for assessing endocrine disrupting chemicals

Toxicology ◽

10.1016/s0300-483x(02)00473-0 ◽

2002 ◽

Vol 181-182 ◽

pp. 389-397 ◽

Cited By ~ 7

Author(s):

John Ashby

Keyword(s):

Endocrine Disrupting Chemicals ◽

Endocrine Disrupting

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Irisin in the primate hypothalamus and its effect on GnRH in vitro

Journal of Endocrinology ◽

10.1530/joe-18-0574 ◽

2019 ◽

Vol 241 (3) ◽

pp. 175-187 ◽

Cited By ~ 6

Author(s):

Fazal Wahab ◽

Ikram Ullah Khan ◽

Ignacio Rodriguez Polo ◽

Hira Zubair ◽

Charis Drummer ◽

...

Keyword(s):

Rhesus Monkeys ◽

Peroxisome Proliferator ◽

Developmentally Regulated ◽

Peroxisome Proliferator Activated Receptor ◽

Reproductive Effects ◽

Reproductive Axis ◽

Hypothalamic Cells ◽

Endocrine Factor

Irisin, encoded by the FNDC5 gene, is a recently discovered endocrine factor mainly secreted as a myokine and adipokine. However, irisin/FNDC5 expression has also been reported in different other organs including components of the reproductive axis. Yet, there is the scarcity of data on FNDC5/irisin expression, regulation and its reproductive effects, particularly in primates. Here, we report the expression of FNDC5/irisin, along with PGC1A (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) and ERRA (estrogen-related receptor alpha), in components of the reproductive axis of marmoset monkeys. Hypothalamic FNDC5 and ERRA transcript levels are developmentally regulated in both male and female. We further uncovered sex-specific differences in FNDC5, ERRA and PGC1A expression in muscle and the reproductive axis. Moreover, irisin and ERRα co-localize in the marmoset hypothalamus. Additionally, in the arcuate nucleus of rhesus monkeys, the number of irisin+ cells was significantly increased in short-term fasted monkeys as compared to ad libitum-fed monkeys. More importantly, we observed putative interaction of irisin-immunoreactive fibers and few GnRH-immunoreactive cell bodies in the mediobasal hypothalamus of the rhesus monkeys. Functionally, we noted a stimulatory effect of irisin on GnRH synthesis and release in mouse hypothalamic neuronal GT1-7 cells. In summary, our findings show that FNDC5 and irisin are developmentally, metabolic-status dependently and sex-specifically expressed in the primate hypothalamic–pituitary–gonadal axis and exert a stimulatory effect on GnRH expression and release in mouse hypothalamic cells. Further studies are required to confirm the reproductive effects of irisin in vivo and to illuminate the mechanisms of its regulation.

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In vitro immunization approach to generate specific murine monoclonal IgG antibodies

10.1101/2020.11.24.393728 ◽

2020 ◽

Author(s):

Sophia Michelchen ◽

Burkhard Micheel ◽

Katja Hanack

Keyword(s):

Monoclonal Antibodies ◽

Legionella Pneumophila ◽

B Lymphocyte ◽

Laboratory Animals ◽

Igg Antibody ◽

Simplified Approach ◽

Humoral Immune ◽

Viral Coat

AbstractGenerating monoclonal antibodies to date is a time intense process requiring immunization of laboratory animals. The transfer of the humoral immune response into in vitro settings shortens this process and circumvents the necessity of animal immunization. However, orchestrating the complex interplay of immune cells in vitro is very challenging. We aimed for a simplified approach focusing on the protagonist of antibody production: the B lymphocyte. We activated purified murine B lymphocytes in vitro with combinations of antigen and stimuli. Within ten days of culture we induced specific IgM and IgG antibody responses against a viral coat protein. Permanently antibody-producing hybridomas were generated. Furthermore we used this method to induce a specific antibody response against Legionella pneumophila. We thus established an effective protocol to generate monoclonal antibodies in vitro. By overcoming the necessity of in vivo immunization it may be the first step towards a universal strategy to generate antibodies from various species.

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