Progress 03/01/16 to 08/31/20
Outputs
Target Audience:Laboratory instruction of technical staff, undergraduate and graduate students, and postdoctoral fellows on animal experimentation and diverse laboratory techniques. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Professional development activities attended:All planned conferences for 2020 were cancelled due to COVID-19 (see details in dissemination section below). Training opportunities:Training of 2 undergraduate students, a graduate student and a postdoctoral fellow in large animal experimentation and several laboratory techniques. How have the results been disseminated to communities of interest?All planned conferences for 2020 were cancelled due to COVID-19 2020*Symposium Talk.Emerging bisphenols and placental trophoblast dysfunction.Society for the Study of Reproduction, Ottowa, Canada. July 12*Cancelled due to COVID19 pandemic. 2020*Rising Star Symposium Talk.Endocrine disrupting chemicals & pregnancy: Hijacking the placenta.Gordon Research Conference Cellular and Molecular Mechanisms of Toxicity. Andover, NH. June 3*Cancelled due to COVID19 pandemic. 2020*Symposium Talk.Knowledge Gaps in Obesogenic Endocrine Disrupting Chemicals.Annual Meeting of the Endocrine Society, San Francisco, CA. March 28*Cancelled due to COVID19 pandemic. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
Laboratory and participants: Over the past year, a postdoctoral fellow, a technician and 2 undergraduate students have continued working on this project. Research: Objectives 1 and 2 are now partially completed as we have evidence of bisphenol S disrupting placental function and fetal growth. This work was published previously. We have continued to work in the characterization of the feto-maternal transfer of bisphenols and have published the results in a peer-reviewed publication in 2019. We have also followed up the toxicokinetic work and developed a pregnancy physiologically-based toxicokinetic model. Additionally, we have expanded our interest on stressors that may affect placental function and have begun studies to understand the effect of pre-conceptional nutrition on pregnancy function and effect of shearing on lamb birth weight. We have published a manuscript, have a manuscript under review and another manuscript in preparation. We have presented this work in professional societies. Products: Directly linked to this work, we have published a peer-reviewed publication in Animal 2020 and a review article in Trends in Endocrinology and Metabolism in 2020. We have also presented 4abstracts at theAnnual Meeting of the Society of Toxicology. See products section for details. Leveraging funds to apply for extramural funding opportunities: In combination with preliminary data from the Hatch MICL02383, the following extramural grant applications were submitted. Not funded. NIEHS (NIH)ViCTER (MPI: Veiga-Lopez/Shikanov) Transdisciplinary study of phthalate mixtures on ovarian function Not funded NIMHD (NIH) R21 (PI:Veiga-Lopez)Oxysterols and racial disparities during pregnancy Not funded NIEHS (NIH) R21 (PI:Veiga-Lopez)Ovarian gap junction disruption and chemical exposures Pending. NIHES (NIH) Administrative Supplement (PI:Veiga-Lopez)Emerging phthalates and placental function
Publications
- Type:
Journal Articles
Status:
Accepted
Year Published:
2020
Citation:
Rosales Nieto C, Mantey A, Makela B, Byrem T, Ehrhardt R, Veiga-Lopez A*. Shearing during late pregnancy increases size at birth but does not alter placental endocrine responses in sheep. Animal (Cambridge) 2020, 14:799-806
- Type:
Journal Articles
Status:
Accepted
Year Published:
2020
Citation:
Gingrich J, Ticiani E, Veiga-Lopez A*. Placenta disrupted: endocrine disrupting chemicals and pregnancy. Trends in Endocrinology and Metabolism 31:508-524
- Type:
Journal Articles
Status:
Under Review
Year Published:
2020
Citation:
Rosales Nieto C, Mantey A, Makela B, Byrem T, Ehrhardt R, Veiga-Lopez A*. Pre-conceptional diet manipulation and fetus number can influence placenta endocrine function in the sheep. Domestic Animal Endocrinology (under review).
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2020
Citation:
Gingrich J, Pu Y, Veiga-Lopez A. A modified parachute assay for accurate assessment of gap junction intercellular communication in placental trophoblast cells. 59th Annual Meeting of the Society of Toxicology, Anaheim, CA, 15-19 March 2020. Abst # 1808 [meeting cancelled due to COVID19].
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2020
Citation:
Pu Y, Veiga-Lopez A. A 3-dimensional microfluidic platform for modeling human extravillous trophoblast invasion and toxicological testing. 59th Annual Meeting of the Society of Toxicology, Anaheim, CA, 15-19 March 2020. Abst # 1275/P450. [meeting cancelled due to COVID19].
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2020
Citation:
Ticiani E, Gingrich J, Pu Y, Veiga-Lopez A. Bisphenol S impairs human cytotrophoblast syncytialization through competitive epidermal growth factor receptor binding. 59th Annual Meeting of the Society of Toxicology, Anaheim, CA, 15-19 March 2020. Abst # 1276/P711. [meeting cancelled due to COVID19].
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2020
Citation:
Filipovic D, Gingrich J, Bhattacharya S, Veiga-Lopez A. Development and systematic comparison of pregnancy physiologically based toxicokinetic models for bisphenols A and S. 59th Annual Meeting of the Society of Toxicology, Anaheim, CA, 15-19 March 2020. Abst # 1594/P565. [meeting cancelled due to COVID19].
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Progress 10/01/18 to 09/30/19
Outputs
Target Audience:Laboratory instruction of technical staff, undergraduate and graduate students, and postdoctoral fellows on animal experimentation and diverse laboratory techniques. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Professional development activities attended: 07/2019 Society for the Study of Reproduction, San Jose, CA. 05/2019 Organization for the Study of Sex Differences Annual Meeting. Washington DC. 03/2019 Annual Society for the Study of Toxicology Meeting Training opportunities: Training of three undergraduate student, technical staff and postdoctoral fellow in large animal experimentation and several laboratory techniques. How have the results been disseminated to communities of interest?The following invited and symposium talks have targeted audiences ranging from scientific audiences to audiences with agricultural and veterinary backgrounds: 2019 Invited Seminar. Toxic effects of plastics during fetal development: the emergent role of the placenta. Medical School, University of San Martin de Porres, Lima, Peru. March 4. 2019 Invited Seminar. Emerging bisphenols & placental dysfunction. University of Arkansas, Little Rock, AR. February 12. 2018 Invited Seminar. Gestational bisphenols: is the placenta at risk? Michigan Center on Lifestage Environmental Exposures and Disease (M-LEEaD) Seminar Series. Public Health School University of Michigan, Ann Arbor, MI. November 19. 2018 Invited Seminar. Bisphenols & pregnancy; are the fetus and the placenta at risk? University of Illinois at Chicago, Chicago, IL. October 25. What do you plan to do during the next reporting period to accomplish the goals? Increase the number of laboratory personnel, including a second postdoctoral fellow and an undergraduate student. Continue leveraging the obtained preliminary data into competitive extramural funding opportunities. Follow up experimentation, including mechanistic insights of BPS placental disruption (already underway).
Impacts
What was accomplished under these goals?
Laboratory and participants: Over the past year, a postdoctoral fellow, a technician and 2 undergraduate students have continued working on this project. Research: Objectives 1 and 2 are now partially completed as we have evidence of bisphenol S disrupting placental function and fetal growth. This work was published previously. We have continued to work in the characterization of the feto-maternal transfer of bisphenols and have published the results in a peer-reviewed publication (see details below). We are currently validating the RNA sequencing analyses and have identified a specific pathway that disrupts the effect of BPS on placental function. Additionally, we have expanded our interest on stressors that may affect placental function and have begun studies to understand the effect of pre-conceptional nutrition on pregnancy function and effect of shearing on lamb birth weight. We have a manuscript under review and another manuscript in preparation. We have presented this work in professional societies. Products: Directly linked to this work, we have published a peer-reviewed publication in Chemosphere in 2019 and a review article in Trends in Endocrinology and Metabolism in 2018. We have also presented 4 abstracts at different conferences, including: the Annual Meeting of the Society of Toxicology, the Future ToxIV Predictive Toxicology for Healthy Children Conference, the Pediatric Academic Societies Annual Meeting, and the Endocrine and Reproductive Biology Society of Western Australia Symposium. See products section for details. Leveraging funds to apply for extramural funding opportunities: In combination with preliminary data from the Hatch MICL02383, the following extramural grant applications were submitted; two of which were funded. Not funded. NIEHS (NIH)ViCTER (MPI: Veiga-Lopez/Shikanov) Transdisciplinary study of phthalate mixtures on ovarian function
Publications
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2018
Citation:
Gingrich J, Filipovic D, Conolly R, Bhattacharya S, Veiga-Lopez A. A physiologically-based toxicokinetic pregnancy model for bisphenol S. Future ToxIV Predictive Toxicology for Healthy Children. Crystal City, VA, November 14-16, 2018.
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2019
Citation:
Gingrich J, Pu Y, Ehrhardt R, Karthikraj R, Kannan K, Veiga-Lopez A. Comparative toxicokinetic study of three bisphenols (BPA, BPS, and BPF) in a sheep pregnancy model. 58th Annual Meeting of the Society of Toxicology, Baltimore, MD, 10-14 March 2019. Abst # 3119/P693.
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2019
Citation:
Sethuraman V, Pu Y, Jing J, Long R, Olomu I, Veiga-Lopez A. Cholesterol and sterol ABC transporters responsiveness to syncytialization is blunted in term pre-eclamptic human cytotrophoblasts. Pediatric Academic Societies Annual Meeting, Baltimore, MD, April 24 - May 1, 2019. Abstr # 237.
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2019
Citation:
Rosales-Nieto C, Ehrhardt E, Makela B, May KJ, Veiga-Lopez A. Shearing during late pregnancy increases size at birth but does not alter placental endocrine responses in sheep. Endocrine and Reproductive Biology Society of Western Australia Symposium 2019, Perth, Australia.
- Type:
Journal Articles
Status:
Accepted
Year Published:
2019
Citation:
Gingrich J, Pu Y, Ehrhardt R, Karthikraj R, Kannan K, Veiga-Lopez A. Toxicokinetics of bisphenol A, bisphenol S, and bisphenol F in a pregnancy sheep model. Chemosphere 2019, 220:185-194
- Type:
Journal Articles
Status:
Accepted
Year Published:
2019
Citation:
Mossa F, Latham K, Ireland JJ, Veiga-Lopez A. Undernutrition and hyperandrogenism during pregnancy: role in programming of cardiovascular disease and infertility. Mol Rep Dev. 2019 Jul 25. doi: 10.1002/mrd.23239. [Epub ahead of print] �co-corresponding authors
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Progress 10/01/17 to 09/30/18
Outputs
Target Audience:Laboratory instruction of technical staff, undergraduate and graduate students, and postdoctoral fellows on animal experimentation and diverse laboratory techniques. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Leveraging funds to apply for extramural funding opportunities: In combination with preliminary data from the Hatch MICL02383, the following extramural grant applications were submitted; two of which were funded. Funded. 2017 NIEHS/NIH R01 (PI: Veiga-Lopez) Placental adaptive mechanisms to environmental exposures. 09/2018-08/2023. $1,900,000 Funded. 2017 Michigan Alliance for Animal Agriculture #AA18-035 (co-PI: Ehrhardt/Veiga-Lopez) Optimizing nutritional management of sheep to improve reproductive outcomes in accelerated production systems. 02/2018-12/2020. $149,000 Not funded. 2017 NIEHS/NIH RFA R01 (PI: Veiga-Lopez) Placental adaptation to environmental exposures. Scored/discussed. How have the results been disseminated to communities of interest?The following invited and symposium talks have targeted audiences ranging from scientific audiences to audiences with agricultural and veterinary backgrounds: Invited Lecture. Pregnancy-associated glycoprotein profile is altered in twin but not singleton pregnancies after pre-conception diet manipulation. NCERA Sheep Research Committee Annual Meeting, Paris, AR, June 5, 2018. Symposium Talk. Bisphenols and placental trophoblast dysfunction. Reproduction Symposium, Annual Joint Meeting for the International Society of Exposure Science (ISES) and International Society for Environmental Epidemiology (ISEE). Ottawa, Canada. August 28, 2018. What do you plan to do during the next reporting period to accomplish the goals?Increase the number of laboratory personnel, including a second postdoctoral fellow and an undergraduate student. Continue leveraging the obtained preliminary data into competitive extramural funding opportunities. Follow up experimentation, including pharmacokinetics experiments (already underway) to understand maternal-fetal transfer
Impacts
What was accomplished under these goals?
Laboratory and participants: Over the past year, a postdoctoral fellow, a graduate student, a technician and one undergraduate student have continued working on this project. One of the undergraduate students (Alex Mantey) received a Summer Fellowship to work on this project. Research: Objectives 1 and 2 are now partially completed as we have evidence of bisphenol S disrupting placental function and fetal growth. This work has been published in a peer-reviewed publication (see details below). We are currently finalizing RNA sequencing analyses that will allow us to better understand the underlying mechanisms of this disruption. Additionally, we have expanded our interest on stressors that may affect placental function and have begun studies to understand the effect of pre-conceptional nutrition on pregnancy function. We have presented some of this work in professional societies. Products: Directly linked to this work, we have published a peer-reviewed publication in Archives of Toxicology in 2018 and a review article in Trends in Endocrinology and Metabolism in 2018. We have also presented 2 abstracts at the Annual Meeting of the American Society for Animal Science. See products section for details.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Gingrich J, Pu Y, Roberts J, Karthikraj R, Kannan K, Ehrhardt R, Veiga-Lopez A. Gestational bisphenol S impairs placental endocrine function and the fusogenic trophoblast signaling pathway. Archives of Toxicology 2018, 92:1861-1876.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2018
Citation:
Rosales-Nieto C, Ehrhardt E, Makela B, May KJ, Veiga-Lopez A. Pregnancy-associated glycoprotein profile is altered in twin but not singleton pregnancies after pre-conception diet manipulation. American Society of Animal Science, Vancouver, Canada, 8-12 July 2018.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2018
Citation:
Rosales Nieto C, Ehrhardt E, Makela B, Mantey A, Veiga-Lopez A. Impact of maternal dietary energy excess and deficit prior to mating on size at birth and pre-weaning growth in prolific sheep. American Society of Animal Science, Vancouver, Canada, 8-12 July 2018.
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Progress 10/01/16 to 09/30/17
Outputs
Target Audience:Laboratory instruction of undergraduate students and technical staff on animal experimentation and related techniques. Scientist and veterinarians in the field of theriogenology. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?As part of this project, we have collaborated with Dr. Richard Ehrhardt (Animal Science, Michigan State University). He has trained my team on how to catheterize the fetal compartemnt to be able to monitor fetal-maternal communication in real time. These preliminary data are currently under analysisa and will be presented next year. Invited talk: Invited Lecture. Circulating pregnancy associated glycoproteins to assess placental function in sheep. NCERA Sheep Research Committee Annual Meeting, Michigan State University, East Lansing, Michigan. June 11, 2017 How have the results been disseminated to communities of interest?The results have been presented at a scientific national conference (Society of Toxicology) What do you plan to do during the next reporting period to accomplish the goals?We will be completing partially developed aims 1 and 2. We will begin to set up experiments planned in aim 3. As part of these experiments, cell culture work will be initiated, including standadization and validation of the cell models to be used. We will also be conducting pharmacokinetics studies as part of the newly established collaboration with Dr. Ehrhardt.
Impacts
What was accomplished under these goals?
Research: Objective 1 and 2 were partially completed and presented in the form of a peer-reviewed manuscript (Theriogenology) and an abstract (Society of Toxicology). We are currently finalizing additional analyses that will allow us to better characterize the placental disruption upon gestational exposures to BPA and BPA replacement chemicals. Products: Under this goals, we have published a peer-reviewed publication (Theriogenology) and an abstract (Society of Toxicology). Leveraging funds to apply for extramural funding opportunities: 06/2017 - NIEHS/NIH RFA (ePOD) - (PI: Veiga-Lopez). Endocrine disruptor exposure and placental dysfunction
Publications
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Gingrich J, Pu Y, Veiga-Lopez A. Gestational exposure to BPS, but not BPA, impairs placental endocrine function in sheep. 56th Annual Meeting of the Society of Toxicology, Baltimore (MD), 12-16 March 2017. Abst # 2215.
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Roberts J, May K, Veiga-Lopez A. Time-dependent changes in pregnancy associated glycoproteins and progesterone in commercial crossbred sheep. Theriogenology 2017 89:271-279
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Progress 03/01/16 to 09/30/16
Outputs
Target Audience:Laboratory instruction of undergraduate student, technical staff, and postdoctoral fellow on animal experimentation and diverse laboratory techniques. Scientist and veterinarians in the field of theriogenology. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Training opportunities: • Continuation of one on one trainings of undergraduate student, technical staff and postdoctoral fellow in large animal experimentation and several laboratory techniques. How have the results been disseminated to communities of interest?The results have been communicated in a platform presentation at the Therio Conference 2016: Roberts J, May KJ, Veiga-Lopez A. Time-dependent changes in pregnancy-associated glycoproteins and serum progesterone in a commercial crossbred sheep during pregnancy and the postpartum period. Society for Theriogenology. Therio Conference 2016, Ashville, North Carolina, 27-30 July 2016. What do you plan to do during the next reporting period to accomplish the goals? Complete analyses on placental proteins. Continue processing of tissues collected from animal experimentation. Publish manuscript on time dependent changes of placental proteins
Impacts
What was accomplished under these goals?
Animal experimentation included the exposure of 25 animals to various endocrine disruptors to study placental outcomes. The animal experimentation phase has now been completed. We have measured a number of placental produced proteins, analyzed results and have reported resutls on the basic profiles for these proteins in a platform communication in the Theriogenology Conference in July 2016. We are currently developing a manuscript to publish these results. In the laboratory, we are currently analyzing the results on the experimentally treated females and begun to process the tissues obtained from the animal experimentation phase. This will be completed in the next year.
Publications
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2016
Citation:
Roberts J, May KJ, Veiga-Lopez A. Time-dependent changes in pregnancy-associated glycoproteins and serum progesterone in a commercial crossbred sheep during pregnancy and the postpartum period. Society for Theriogenology. Therio Conference 2016, Ashville, North Carolina, 27-30 July 2016.
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