The Interface between Cell and Molecular Biology and Animal Agriculture

 

When most people think about agriculture, cell and molecular biology are the last things that come to mind. However, these disciplines are constantly impacting animal agriculture, and livestock species often are valuable models for biomedical research.

 

Today, most investigators give little thought to the interface between biochemistry, cell and molecular biology and agriculture -- much greater emphasis is placed on the biomedical relevance of research than on its relevance to animal agriculture. This likely is due to the changing demographics of the United States. At the turn of the 20th century, 43.5 percent of the U.S. work force was involved in agriculture, as compared with only 2.4 percent by the end of the century. Yet, advances in cell and molecular biology continue to impact animal agriculture, and livestock species often are valuable models for biomedical research. The following are a few examples of how cell and molecular biology interface with animal agriculture.

Dairy Cow

Recombinant DNA technology has been used to develop recombinant bovine somatotropin to enhance the efficiency of milk production.

Recombinant DNA Technology

Recombinant DNA technology has been used to generate effective vaccines and hormones for the livestock industry. For example, a polypeptide derived from the recombinant pseudo-rabies virus glycoprotein has been used for the generation of a pseudo-rabies vaccine for swine. A recombinant DNA vaccine also currently is marketed for the vaccination of horses against West Nile virus, and additional vaccines for livestock, derived from recombinant DNA technology, are being developed.

Recombinant DNA technology also led to the development and use of recombinant bovine somatotropin (bST; growth hormone) in lactating dairy cows to enhance the efficiency of milk production. Although the use of bST may be viewed as controversial, it still is a “success story” for the interface of molecular biology with animal agriculture.

Furthermore, the successful recombinant generation of several reproductive hormones, such as gonadotropins and gonadotropin-releasing hormone, has enhanced the development and efficiency of assisted reproductive technologies in livestock, including artificial insemination, estrous synchronization, in vitro fertilization and embryo transfer.

Molecular Technology

Molecular technologies have allowed the generation of reagents and diagnostic kits previously unavailable for livestock. This includes reagents for diagnostic enzyme-linked immunosorbent assay kits, as well as reverse transcription-polymerase chain reaction and standard PCR. The latter two have been used for identification of viral and microbe infection (e.g., screening pig semen for porcine reproductive and respiratory syndrome virus), as well as genetic diagnosis of embryonic sex prior to embryo transfer.

Cell Biology Technology

Cell biology is being used to examine sperm membrane compositional changes during capacitation and the acrosome reaction to assess sperm quality and to enhance the cryopreservation of livestock sperm and embryos.

Fluorescence-activated cell sorting was used for the commercialization of “sexed” semen, allowing the dairy industry to obtain greater numbers of female offspring for milk production, and helping the beef industry obtain more male offspring for the efficient production of nutrient-dense meat for human consumption.

Functional Genomics

Although the complete genomic sequences for many livestock species are yet to be completed or released, considerable effort is being directed toward identifying quality trait loci and single nucleotide polymorphisms that can be used to enhance genetic selection. At commercial artificial insemination companies, the use of single nucleotide polymorphism chip analysis of sires is becoming routine.

Genetic sex determination currently is utilized, as well as limited “marker assisted selection” for production traits, such as muscle development and intramuscular fat deposition (i.e., meat quality). With second-generation, solid-state DNA sequencing now available, complete transcriptome analysis of various production efficiency traits is on the horizon.

Animal Agriculture
Representation of somatic cell nuclear transfer. Somatic cells are transferred into the perivitelline space of an MII stage-enucleated oocyte, fused and activated, and either cultured or immediately transferred into a recipient.

Transgenesis

The generation of lines of transgenic livestock has not met the expectations initially anticipated, primarily because of low technical efficiency and long generation intervals. It was hoped that transgenic lines could be developed that were either disease-resistant; that produced valuable products (e.g., pharmaceuticals) that could be harvested from milk, blood or eggs in large quantities or that exhibited decreased excretion of compounds detrimental to the environment.

Somatic cell nuclear transfer initially was applied to livestock, and although it has not had the anticipated commercial application, it has provided considerable insight into factors regulating early embryo development. Genetic manipulation of the “donor” cells is more efficient than standard transgenic approaches and has allowed the generation of SCNT-transgenic lines. Some of these are being developed as models for human disease and/or xenotransplantation.

For example, CFTR-null pigs, generated by SCNT, appear to be a better model for human cystic fibrosis than available mouse models, because the CFTR-null piglets develop more of the hallmark pathologies associated with cystic fibrosis in humans.

Recently, infection of early-stage embryos or blastocysts with lentiviral constructs, to either overexpress or “knock down” expression of specific genes, have been reported in cattle and sheep and have promise for more efficient genetic manipulation of livestock, at least for research purposes.

Advances in Biomedical Research

This brief synopsis of how cell and molecular biology technologies are interfacing with animal agriculture is not meant to be all-inclusive or exhaustive, but rather to highlight areas that have already or have the potential to impact livestock production. However, a discussion of this “interface” would not be complete without providing examples of how livestock species have helped to advance biomedical research.

For example, many assisted reproduction technologies, such as artificial insemination, cryopreservation of gametes and embryo transfer, initially were developed in livestock species before being applied to humans. There has been, and continues to be, a strong interface between efforts to improve human fertility and similar efforts in animal agriculture.

Sheep
The pregnant sheep has many attributes that make it a relevant experimental model. Photo credit: Carly Lesser and Art Drauglis. 

Another example is the use of livestock, especially sheep, to investigate the physiology of gestation. The pregnant sheep has many attributes that make it a relevant experimental model: It is a long gestational mammal like the human; it often gives rise to a single offspring that has similar organ developmental maturity to the human newborn; and it can be manipulated surgically such that chronic instrumentation (vascular catheters, flow probes, etc.) of the fetus allows repetitive sampling on both sides of the placenta under nonanesthetized steady-state conditions. This animal model has provided considerable insight into placental nutrient transfer, fetal-nutrient utilization and the impaired fetal physiology associated with intrauterine growth restriction.

Additionally, swine provide a very relevant model for studying the development of cardiovascular disease, and chickens are being used as a natural model for ovarian cancer.

Clearly, animal agriculture has benefited and continues to benefit from advances made in cell and molecular biology and livestock species have served as valuable and relevant animal models for biomedical research. And, although the percentage of the U.S. work force involved with agriculture continues to decline, agriculture still is an important and required component of everyday life. The interface between cell and molecular biology and agriculture has been robust, and should continue to be, with both scientific disciplines benefiting from each other.

Russell V. Anthony (Russ.Anthony@Colostate.edu) is the Hill professor in the department of biomedical sciences at Colorado State University. Scott L. Pratt (scottp@clemson.edu) is an assistant professor in the department of animal and veterinary science at Clemson University.

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