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Scientists make reproduction breakthrough (Released: 8/13/98)

by Renu Aldrich, Office of University Communications.

Storrs , Conn. -- Technological advances made by the University of Connecticut Transgenic Animal Facility have allowed a heifer to become a mother of two before puberty, alleviating one of the obstacles toward using transgenic cattle to produce milk therapeutic to humans.

The techniques also could be beneficial in the treatment of female infertility.

"If we are able to use the many eggs the cow produces that are destined to degenerate, we can save a lot of time and money in the reproduction of cows used as bioreactors or human organ donors," says Dr. Xiangzhong (Jerry) Yang, professor of animal science. "This will also save money for the patient and the consumer. The process and the techniques we used may further benefit breeding programs for domestic livestock, the preservation of endangered species and the treatment of infertility in women."

Yang presented the data at the annual meeting of the Society for the Study of Reproduction at Texas A&M University on August 11.

Yang and his team collected eggs from the ovaries of a two-month old calf and then matured and fertilized them through an in vitro method. The viable embryos were carried to term by surrogate mothers at Fairvue Farm in Woodstock, Conn. Two calves, named Chuck and Gus, were born healthy one day apart in the middle of May B their mother was just 11 months old. Another pre-pubescent heifer became a mother of four successfully in July.

The first study to produce embryos and progeny from juvenile calves was reported in Australia in 1991. Currently, there are a handful of laboratories in the world actively pursuing research using calf eggs, or oocytes, but UConn is one of only two laboratories to successfully produce progeny from juvenile calves. The technology is focused on producing viable eggs from a cow before puberty to significantly reduce the time line for the creation of a transgenic herd. A transgenic animal is one that has had DNA introduced into one or more of its cells artificially.

"The length of time it takes to produce such a herd is the main obstacle to the use of transgenic cattle for the production of recombinant therapeutic proteins in cow's milk," says Dr. Yann Echelard, vice director of research at Genzyme Transgenic Corp., which partially funded the project.

"While it may cost over a $1,000,000 to produce a transgenic calf, this technology will permit the reproduction in large numbers of the valuable calf relatively inexpensively. It would also save the company at least one year in each generation to reproduce their valuable animals that may mean millions of dollars to the company," Yang says.

The actual retrieval of the eggs may be simplified when the animals reach six or seven months of age. While the first two collections from the mother cow were performed surgically, subsequent collections were done by a non-invasive procedure known as ultrasound-guided transvaginal oocyte pick-up (OPU). With OPU, eggs may be collected from a heifer or cow once or even twice weekly - meaning that as many as 1,000 eggs per year may be collected from a single female. The embryos may also be manipulated to produce offspring of a desired gender or be frozen for embryo transfer at a later time or at a different location.

The ability to use in vitro matured oocytes in humans would avoid the need for women to be hormonally stimulated, a process that costs several thousands of dollars and sometimes can cause physiological and psychological side effects, Yang says. Most human infertility clinics currently use in vivo matured oocytes -- those that are matured within the human body -- for in vitro fertilization because it has been difficult to mature oocytes with the in vitro method.

"I hope an efficient system to mature calf oocytes will have some implication in humans," he says.

The UConn Transgenic Animal Facility is affiliated with the UConn Biotechnology Center and the College of Agriculture and Natural Resources. The facility's goal is to be a Center of Excellence for research, training and collaboration in transgenic production and related animal biotechnologies.

The Facility is one of only a few academic transgenic facilities in the world that works on transgenic farm animals and other non-rodent species such as the rabbit. Transgenic technology has great potential for breeding disease resistance-transgenic animals, or animals with more lean meat or better milk quality. The production of transgenic farm animals has been encouraged recently by the pharmaceutical industry's investment in producing transgenic farm animals as bioreactors or human organ donors. Yang's research was supported in part by Genzyme Transgenic Corporation of Framingham, Mass. and a grant from the U.S. Department of Agriculture.