Nutritional studies of the embryo during early organogenesis with normal embryos and embryos exhibiting yolk sac dysfunction
Abstract
In 1961 we reported that heterologous kidney antiserum when injected into pregnant rats resulted in wide spectrum of congenital malformations. Further studies identified that it was the IgG component of the antiserum that was teratogenic and that complement was not necessary to produce the teratogenic effect. Labeled antibody studies demonstrated that the kidney antiserum localized in the kidney and in the visceral yolk sac (VYS) and parietal yolk sac placentas. Preparation of yolk sac (YS) antiserum proved to be more potent than the kidney antiserum. Adsorption studies with VYS and parietal yolk sac antiserum revealed that the site of the teratogenic process was located in the VYS. In vitro embryo culture experiments demonstrated that direct injection of the teratogenic antibody into the amniotic or YS cavity did not injure the embryo, thus indicating that the teratogenic antibody had to come in contact with the absorptive surface of the VYS. Collaboration with Dr. John Lloyd demonstrated that teratogenic antibody interfered with the process of pinocytosis and the delivery of amino acids (AA) to the developing embryo. Our studies into the nature of the source of AA for the embryo indicated that in some instances > 95% of the AA present in the developing embryo were derived from maternal proteins and the remainder from free AA in the maternal serum. We also demonstrated that embryonic methionine was derived primarily from the digestion of maternal serum proteins but that more of the methionine was diverted from the synthesis of embryonic proteins, supporting the view that it has important functions other than the synthesis of proteins. All these studies focus on the role of the YS in human development and whether human YS dysfunction may play a role in the pathogenesis of congenital malformations. Further studies on the delivery of AA to the embryo are warranted to determine whether certain AA are in short supply in maternal serum and place the embryo at risk if nutritional alterations in the maternal environment occurs. Furthermore, the YS may be an organ whose role might offer opportunities for pregnancy control.
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Experiments in the rat have revealed that more than 95% of amino acids transported during the period of organogenesis are derived from the uptake and subsequent breakdown of maternal proteins by the yolk sac.
“Experiments in the rat have revealed that more than 95% of amino acids transported during the period of organogenesis are derived from the uptake and subsequent breakdown of maternal proteins by the yolk sac (59,344).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [59]
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Placental Origins of Chronic Disease
Burton, G. J., Fowden, A. L., & Thornburg, K. L. (2016) · Physiological Reviews · doi:10.1152/physrev.00029.2015 · Cited by 717 · see citing works
- Authors
- Brent, R. L., & Fawcett, L. B.
- Affiliations
- Thomas Jefferson University (US)
- Venue
- The Journal of Pediatrics
- Publisher
- Elsevier BV
- Published
- 1998-03
- Volume
- 132
- Issue
- 3
- Pages
- S6-S16
- ISSN
- 0022-3476 (ISSN-L)
- OpenAlex
- W2016025872
- Cited by
- 40
- References
- 96
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 3 · 2020: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 3 · 2012: 1
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Pediatrics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hd029902-03)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD29902)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- yolk sac, embryo nutrition, early organogenesis, visceral yolk sac, pinocytosis, maternal serum proteins, congenital malformations, pregnancy control
- MeSH terms
- Congenital Abnormalities, Amino Acids, Animals, Disease Models, Animal, Energy Metabolism, Female, Embryonic and Fetal Development, Fetal Growth Retardation, Humans, Infant, Newborn, Maternal-Fetal Exchange, Pinocytosis, Pregnancy, Yolk Sac, Rats
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