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Jodi A Flaws - One of the best experts on this subject based on the ideXlab platform.
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transgenerational effects of endocrine disrupting chemicals on male and Female Reproduction
Endocrinology, 2019Co-Authors: Emily Brehm, Jodi A FlawsAbstract:Endocrine-disrupting chemicals are known to interfere with normal reproductive function and hormone signaling. Phthalates, bisphenol A, pesticides, and environmental contaminants such as polychlorinated biphenyls and dioxins are known endocrine-disrupting chemicals that have been shown to negatively affect both male and Female Reproduction. Exposure to these chemicals occurs on a daily basis owing to these compounds being found in plastics, personal care products, and pesticides. Recently, studies have shown that these chemicals may cause transgenerational effects on Reproduction in both males and Females. This is of concern because exposure to these chemicals prenatally or during adult life can negatively impact the reproductive health of future generations. This mini-review summarizes the endocrine-disrupting chemicals that humans are exposed to on a daily basis and what is known about the transgenerational effects that these chemicals may have on male and Female Reproduction.
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The epigenetic impacts of endocrine disruptors on Female Reproduction across generations
Biology of reproduction, 2019Co-Authors: Saniya Rattan, Jodi A FlawsAbstract:Humans and animals are repeatedly exposed to endocrine disruptors, many of which are ubiquitous in the environment. Endocrine disruptors interfere with hormone action; thus, causing non-monotonic dose responses that are atypical of standard toxicant exposures. The Female reproductive system is particularly susceptible to the effects of endocrine disruptors. Likewise, exposures to endocrine disruptors during developmental periods are particularly concerning because programming during development can be adversely impacted by hormone level changes. Subsequently, developing reproductive tissues can be predisposed to diseases in adulthood and these diseases can be passed down to future generations. The mechanisms of action by which endocrine disruptors cause disease transmission to future generations are thought to include epigenetic modifications. This review highlights the effects of endocrine disruptors on the Female reproductive system, with an emphasis on the multi- and transgenerational epigenetic effects of these exposures.
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subchronic exposure to di 2 ethylhexyl phthalate and diisononyl phthalate during adulthood has immediate and long term reproductive consequences in Female mice
Toxicological Sciences, 2019Co-Authors: Catheryne Chiang, Jodi A FlawsAbstract:: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in a variety of consumer products. This is concerning because DEHP is an endocrine disruptor and ovarian toxicant. Diisononyl phthalate (DiNP) is a DEHP replacement that is a rising human toxicant due to its increased use as a DEHP substitute. However, little is known about the effects of DEHP or DiNP exposure during adulthood on Female Reproduction. Thus, this study tested the hypothesis that DEHP or DiNP exposure during adulthood has long-term consequences for Female Reproduction in mice. Adult Female CD-1 mice (39-40 days) were orally dosed with vehicle control (corn oil), DEHP (20 µg/kg/day-200 mg/kg/day), or DiNP (20 µg/kg/day-200 mg/kg/day) for 10 days. Females were paired with untreated male mice for breeding trials immediately post-dosing and again at 3 and 9 months post-dosing. Immediately post-dosing, DEHP and DiNP did not affect fertility. At 3 months post-dosing, DiNP (20 and 100 µg/kg/day and 200 mg/kg/day) significantly disrupted estrous cyclicity, and DiNP and DEHP (20 µg/kg/day) significantly reduced the ability of Females to get pregnant. At 9 months post-dosing, DiNP significantly disrupted estrous cyclicity (100 µg/kg/day), reduced time to mating (100 µg/kg/day-200 mg/kg/day), and borderline reduced percent of Females who produced offspring (20 mg/kg/day). At 9 months post-dosing, DEHP (200 µg/kg/day and 200 mg/kg/day) and DiNP (100 µg/kg/day and 20 and 200 mg/kg/day) increased numbers of male-biased litters. These data show that DEHP and DiNP exposure has long-term consequences for Female Reproduction, even long after cessation of exposure.
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prenatal exposure to di 2 ethylhexyl phthalate causes long term transgenerational effects on Female Reproduction in mice
Endocrinology, 2018Co-Authors: Emily Brehm, Liying Gao, Saniya Rattan, Jodi A FlawsAbstract:Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer in many consumer products. Although DEHP is a known endocrine disruptor, little is known about the effects of DEHP exposure on Female Reproduction. Thus, this study tested the hypothesis that prenatal DEHP exposure affects follicle numbers, estrous cyclicity, and hormone levels in multiple generations of mice. Pregnant CD-1 mice were orally dosed with corn oil (vehicle control) or DEHP (20 and 200 µg/kg/d and 500 and 750 mg/kg/d) from gestational day 11 until birth. The F1 Females were mated with untreated males to create the F2 generation, and the F2 Females were mated with untreated males to create the F3 generation. At 1 year, ovaries, hormones, and estrous cycles were analyzed in each generation. Prenatal DEHP exposure altered estrous cyclicity (750 mg/kg/d), increased the presence of ovarian cysts (750 mg/kg/d), and decreased total follicle numbers (750 mg/kg/d) in the F1 generation. It also decreased anogenital distance (200 µg/kg/d) and altered follicle numbers (200 µg/kg/d and 500 mg/kg/d) in the F2 generation, and it altered estrous cyclicity (20 and 200 µg/kg/d and 500 and 750 mg/kg/d) and decreased folliculogenesis (200 µg/kg/d and 500 mg/kg/d) in the F3 generation. Further, prenatal DEHP increased estradiol levels (F1 and F3), decreased testosterone levels (F1, F2, and F3), decreased progesterone levels (F2), altered gonadotropin hormone levels (F1 and F3), and decreased inhibin B levels (F1 and F3). Collectively, these data show that prenatal exposure to DEHP has multigenerational and transgenerational effects on Female Reproduction and it may accelerate reproductive aging.
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exposure to an environmentally relevant phthalate mixture causes transgenerational effects on Female Reproduction in mice
Endocrinology, 2017Co-Authors: Changqing Zhou, Liying Gao, Jodi A FlawsAbstract:Phthalates are used in consumer products and are known endocrine-disrupting chemicals. However, limited information is available on the effects of phthalate mixtures on Female Reproduction. Previously, we developed a phthalate mixture made of 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% di-isononyl phthalate, 8% di-isobutyl phthalate, and 5% benzylbutyl phthalate that mimics human exposure. We tested the effects of prenatal exposure to this mixture on reproductive outcomes in first-filial-generation (F1) Female mice and found that it impaired reproductive outcomes. However, the impact of this exposure on second-filial-generation (F2) and third-filial-generation (F3) Females was unknown. Thus, we hypothesized that prenatal exposure to the phthalate mixture induces multigenerational and transgenerational effects on Female Reproduction. Pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200 µg/kg/d, 200 and 500 mg/kg/d) daily from gestational day 10 to birth. Adult F1 Females born to these dams were used to generate the F2 generation and adult F2 Females born to F1 Females were used to generate the F3 generation. F2 and F3 Females were subjected to tissue collections and fertility tests. Prenatal phthalate mixture exposure increased uterine weight, anogenital distance, and body weight; induced cystic ovaries; and caused fertility complications in the F2 generation. It also increased uterine weight, decreased anogenital distance, and caused fertility complications in the F3 generation. These data suggest that prenatal exposure to the phthalate mixture induces multigenerational and transgenerational effects on Female Reproduction.
Subba Reddy Palli - One of the best experts on this subject based on the ideXlab platform.
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molecular analysis of nutritional and hormonal regulation of Female Reproduction in the red flour beetle tribolium castaneum
Insect Biochemistry and Molecular Biology, 2011Co-Authors: R Parthasarathy, Subba Reddy PalliAbstract:Female Reproduction includes maturation of oocytes and the synthesis of yolk proteins (vitellogenin, Vg) in the fat body and their deposition into the oocytes. Our recent studies showed that juvenile hormone (JH) regulates Vg synthesis and 20-hydroxyecdysone (20E) regulates oocyte maturation in the red flour beetle (Tribolium castaneum). Here, we report on the role of nutritional signaling on vitellogenesis and oogenesis. Comparison of gene expression between fed and starved beetles by microarray analysis showed the up-regulation of genes involved in energy homeostasis and down-regulation of genes involved in egg production in the starved beetles. The RNA interference (RNAi) aided knock-down in the expression of genes involved in insulin and TOR signaling pathways showed that both these signaling pathways play key roles in Vg synthesis and oocyte maturation. Starvation of Female beetles resulted in a block in Vg synthesis but not in the progression of primary oocyte development to the resting stage. Feeding after starvation induced Vg synthesis and the progression of primary oocytes from the resting stage to the mature stage. However, in the beetles where JH or 20E synthesis or action was blocked by RNAi, both Vg synthesis and oocyte maturation were affected suggesting that both these hormones (JH and 20E) and nutritional signaling and their cross-talk regulate vitellogenesis and oogenesis.
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the function of nuclear receptors in regulation of Female Reproduction and embryogenesis in the red flour beetle tribolium castaneum
Journal of Insect Physiology, 2010Co-Authors: Anjiang Tan, Subba Reddy PalliAbstract:Nineteen canonical and two Knirps-like family nuclear receptors (NRs) were identified in the genome of Tribolium castaneum. The current study was conducted to determine the function of these NRs in regulation of Female Reproduction and embryogenesis. RNA interference (RNAi)-aided knock-down in the expression of genes coding for 21 NRs showed that seven NRs E75, hormone receptor 3 (HR3), ecdysone receptor (EcR), ultraspiracle (USP), seven-up (SVP), FTZ transcription factor 1 (FTZ-F1) and hormone receptor 4 (HR4) are required for successful vitellogenesis and oogenesis. Knocking down the expression of genes coding for these seven NRs affected egg production by reducing the levels of vitellogenin mRNAs as well as by affecting the oocyte maturation. Expression of seven additional NRs hormone receptor 96 (HR96), hormone receptor 51 (HR51), hormone receptor 38 (HR38), hormone receptor 39 (HR39), Tailless (Tll), Dissatisfaction (Dsf) and Knirps-like is required for successful embryogenesis. The knock-down in the expression of genes coding for three other NRs (E78, hepatocyte nuclear factor 4, HNF4 and Eagle) partially blocked embryogenesis. This study showed that at least 17 out of the 21 NRs identified in T. castaneum play key roles in Female Reproduction and embryogenesis.
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mode of action of methoprene in affecting Female Reproduction in the african malaria mosquito anopheles gambiae
Pest Management Science, 2010Co-Authors: Hua Bai, Dale B Gelman, Subba Reddy PalliAbstract:BACKGROUND: One of the most studied actions of juvenile hormone (JH) is its ability to modulate ecdysteroid signaling during insect development and metamorphosis. Previous studies in mosquitoes showed that 20-hydroxyecdysone (20E) regulates vitellogenin synthesis. However, the action of JH and its mimics, e.g. methoprene, on Female Reproduction of mosquitoes remains unknown. RESULTS: Here, a major malaria vector, Anopheles gambiae Giles, was used as a model insect to study the action of methoprene on Female Reproduction. Ecdysteroid titers and expression profiles of ecdysone-regulated genes were determined before and after a blood meal. An ecdysteroid peak was detected at 12 h post blood meal (PBM). The maximum expression of ecdysone-regulated genes, such as ecdysone receptor (EcR), hormone receptor 3 (HR3) and vitellogenin (Vg) gene, coincided with the ecdysteroid peak. Interestingly, topical application of methoprene at 6 h PBM delayed ovarian development and egg maturation by suppressing the expression of ecdysone-regulated genes in Female mosquitoes. CONCLUSION: The data suggest that ecdysteroid titers are correlated with Vg synthesis, and methoprene affects vitellogenesis by modulating ecdysteroid action in A. gambiae. Copyright © 2010 Society of Chemical Industry
Steven Russell - One of the best experts on this subject based on the ideXlab platform.
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a crispr cas9 gene drive system targeting Female Reproduction in the malaria mosquito vector anopheles gambiae
Nature Biotechnology, 2016Co-Authors: Andrew Hammond, Roberto Galizi, Kyros Kyrou, Alekos Simoni, Carla Siniscalchi, Dimitris Katsanos, Matthew Gribble, Dean A Baker, Eric Marois, Steven RussellAbstract:Development of a CRISPR/Cas9-based gene drive system in Anopheles gambiae, the main vector for the malaria parasite, paves the way for control of this pest insect. Gene drive systems that enable super-Mendelian inheritance of a transgene have the potential to modify insect populations over a timeframe of a few years. We describe CRISPR-Cas9 endonuclease constructs that function as gene drive systems in Anopheles gambiae, the main vector for malaria. We identified three genes (AGAP005958, AGAP011377 and AGAP007280) that confer a recessive Female-sterility phenotype upon disruption, and inserted into each locus CRISPR-Cas9 gene drive constructs designed to target and edit each gene. For each targeted locus we observed a strong gene drive at the molecular level, with transmission rates to progeny of 91.4 to 99.6%. Population modeling and cage experiments indicate that a CRISPR-Cas9 construct targeting one of these loci, AGAP007280, meets the minimum requirement for a gene drive targeting Female Reproduction in an insect population. These findings could expedite the development of gene drives to suppress mosquito populations to levels that do not support malaria transmission.
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a crispr cas9 gene drive system targeting Female Reproduction in the malaria mosquito vector anopheles gambiae
Nature Biotechnology, 2016Co-Authors: Andrew Hammond, Roberto Galizi, Kyros Kyrou, Alekos Simoni, Carla Siniscalchi, Dimitris Katsanos, Matthew Gribble, Dean A Baker, Eric Marois, Steven RussellAbstract:Gene drive systems that enable super-Mendelian inheritance of a transgene have the potential to modify insect populations over a timeframe of a few years. We describe CRISPR-Cas9 endonuclease constructs that function as gene drive systems in Anopheles gambiae, the main vector for malaria. We identified three genes (AGAP005958, AGAP011377 and AGAP007280) that confer a recessive Female-sterility phenotype upon disruption, and inserted into each locus CRISPR-Cas9 gene drive constructs designed to target and edit each gene. For each targeted locus we observed a strong gene drive at the molecular level, with transmission rates to progeny of 91.4 to 99.6%. Population modeling and cage experiments indicate that a CRISPR-Cas9 construct targeting one of these loci, AGAP007280, meets the minimum requirement for a gene drive targeting Female Reproduction in an insect population. These findings could expedite the development of gene drives to suppress mosquito populations to levels that do not support malaria transmission.
Andrew Hammond - One of the best experts on this subject based on the ideXlab platform.
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a crispr cas9 gene drive system targeting Female Reproduction in the malaria mosquito vector anopheles gambiae
Nature Biotechnology, 2016Co-Authors: Andrew Hammond, Roberto Galizi, Kyros Kyrou, Alekos Simoni, Carla Siniscalchi, Dimitris Katsanos, Matthew Gribble, Dean A Baker, Eric Marois, Steven RussellAbstract:Development of a CRISPR/Cas9-based gene drive system in Anopheles gambiae, the main vector for the malaria parasite, paves the way for control of this pest insect. Gene drive systems that enable super-Mendelian inheritance of a transgene have the potential to modify insect populations over a timeframe of a few years. We describe CRISPR-Cas9 endonuclease constructs that function as gene drive systems in Anopheles gambiae, the main vector for malaria. We identified three genes (AGAP005958, AGAP011377 and AGAP007280) that confer a recessive Female-sterility phenotype upon disruption, and inserted into each locus CRISPR-Cas9 gene drive constructs designed to target and edit each gene. For each targeted locus we observed a strong gene drive at the molecular level, with transmission rates to progeny of 91.4 to 99.6%. Population modeling and cage experiments indicate that a CRISPR-Cas9 construct targeting one of these loci, AGAP007280, meets the minimum requirement for a gene drive targeting Female Reproduction in an insect population. These findings could expedite the development of gene drives to suppress mosquito populations to levels that do not support malaria transmission.
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a crispr cas9 gene drive system targeting Female Reproduction in the malaria mosquito vector anopheles gambiae
Nature Biotechnology, 2016Co-Authors: Andrew Hammond, Roberto Galizi, Kyros Kyrou, Alekos Simoni, Carla Siniscalchi, Dimitris Katsanos, Matthew Gribble, Dean A Baker, Eric Marois, Steven RussellAbstract:Gene drive systems that enable super-Mendelian inheritance of a transgene have the potential to modify insect populations over a timeframe of a few years. We describe CRISPR-Cas9 endonuclease constructs that function as gene drive systems in Anopheles gambiae, the main vector for malaria. We identified three genes (AGAP005958, AGAP011377 and AGAP007280) that confer a recessive Female-sterility phenotype upon disruption, and inserted into each locus CRISPR-Cas9 gene drive constructs designed to target and edit each gene. For each targeted locus we observed a strong gene drive at the molecular level, with transmission rates to progeny of 91.4 to 99.6%. Population modeling and cage experiments indicate that a CRISPR-Cas9 construct targeting one of these loci, AGAP007280, meets the minimum requirement for a gene drive targeting Female Reproduction in an insect population. These findings could expedite the development of gene drives to suppress mosquito populations to levels that do not support malaria transmission.
Emily Brehm - One of the best experts on this subject based on the ideXlab platform.
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transgenerational effects of endocrine disrupting chemicals on male and Female Reproduction
Endocrinology, 2019Co-Authors: Emily Brehm, Jodi A FlawsAbstract:Endocrine-disrupting chemicals are known to interfere with normal reproductive function and hormone signaling. Phthalates, bisphenol A, pesticides, and environmental contaminants such as polychlorinated biphenyls and dioxins are known endocrine-disrupting chemicals that have been shown to negatively affect both male and Female Reproduction. Exposure to these chemicals occurs on a daily basis owing to these compounds being found in plastics, personal care products, and pesticides. Recently, studies have shown that these chemicals may cause transgenerational effects on Reproduction in both males and Females. This is of concern because exposure to these chemicals prenatally or during adult life can negatively impact the reproductive health of future generations. This mini-review summarizes the endocrine-disrupting chemicals that humans are exposed to on a daily basis and what is known about the transgenerational effects that these chemicals may have on male and Female Reproduction.
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prenatal exposure to di 2 ethylhexyl phthalate causes long term transgenerational effects on Female Reproduction in mice
Endocrinology, 2018Co-Authors: Emily Brehm, Liying Gao, Saniya Rattan, Jodi A FlawsAbstract:Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer in many consumer products. Although DEHP is a known endocrine disruptor, little is known about the effects of DEHP exposure on Female Reproduction. Thus, this study tested the hypothesis that prenatal DEHP exposure affects follicle numbers, estrous cyclicity, and hormone levels in multiple generations of mice. Pregnant CD-1 mice were orally dosed with corn oil (vehicle control) or DEHP (20 and 200 µg/kg/d and 500 and 750 mg/kg/d) from gestational day 11 until birth. The F1 Females were mated with untreated males to create the F2 generation, and the F2 Females were mated with untreated males to create the F3 generation. At 1 year, ovaries, hormones, and estrous cycles were analyzed in each generation. Prenatal DEHP exposure altered estrous cyclicity (750 mg/kg/d), increased the presence of ovarian cysts (750 mg/kg/d), and decreased total follicle numbers (750 mg/kg/d) in the F1 generation. It also decreased anogenital distance (200 µg/kg/d) and altered follicle numbers (200 µg/kg/d and 500 mg/kg/d) in the F2 generation, and it altered estrous cyclicity (20 and 200 µg/kg/d and 500 and 750 mg/kg/d) and decreased folliculogenesis (200 µg/kg/d and 500 mg/kg/d) in the F3 generation. Further, prenatal DEHP increased estradiol levels (F1 and F3), decreased testosterone levels (F1, F2, and F3), decreased progesterone levels (F2), altered gonadotropin hormone levels (F1 and F3), and decreased inhibin B levels (F1 and F3). Collectively, these data show that prenatal exposure to DEHP has multigenerational and transgenerational effects on Female Reproduction and it may accelerate reproductive aging.
