Important aspects of placental-specific gene transfer

The placenta is a unique and highly complex organ that develops only during pregnancy and is essential for growth and survival of the developing fetus. The placenta provides the vital exchange of gases and wastes, the necessary nutrients for fetal development, acts as immune barrier that protects ag...

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Bibliographic Details
Published in:Theriogenology 2014-10, Vol.82 (7), p.1043-1048
Main Authors: Kaufman, Melissa R., Albers, Renee E., Keoni, Chanel, Kulkarni-Datar, Kashmira, Natale, David R., Brown, Thomas L.
Format: Article
Language:English
Subjects:
Animals
Blastocyst - physiology
Embryo transfer
Embryo Transfer - methods
Embryo Transfer - veterinary
Female
Gene Expression Regulation, Developmental - physiology
Gene transfer
Gene Transfer Techniques
Green Fluorescent Proteins - metabolism
Lentivirus
Male
Mice
Mice, Inbred C57BL
Placenta
Placenta - metabolism
Preeclampsia
Pregnancy
Trophoblast
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Summary:The placenta is a unique and highly complex organ that develops only during pregnancy and is essential for growth and survival of the developing fetus. The placenta provides the vital exchange of gases and wastes, the necessary nutrients for fetal development, acts as immune barrier that protects against maternal rejection, and produces numerous hormones and growth factors that promote fetal maturity to regulate pregnancy until parturition. Abnormal placental development is a major underlying cause of pregnancy-associated disorders that often result in preterm birth. Defects in placental stem cell propagation, growth, and differentiation are the major factors that affect embryonic and fetal well-being and dramatically increase the risk of pregnancy complications. Understanding the processes that regulate placentation is important in determining the underlying factors behind abnormal placental development. The ability to manipulate genes in a placenta-specific manner provides a unique tool to analyze development and eliminates potentially confounding results that can occur with traditional gene knockouts. Trophoblast stem cells and mouse embryos are not overly amenable to traditional gene transfer techniques. Most viral vectors, however, have a low infection rate and often lead to mosaic transgenesis. Although the traditional method of embryo transfer is intrauterine surgical implantation, the methodology reported here, combining lentiviral blastocyst infection and nonsurgical embryo transfer, leads to highly efficient and placental-specific gene transfer. Numerous advantages of our optimized procedures include increased investigator safety, a reduction in animal stress, rapid and noninvasive embryo transfer, and higher a rate of pregnancy and live birth.
ISSN:0093-691X
1879-3231
DOI:10.1016/j.theriogenology.2014.07.010