The development of "surrogacy" technology has allowed excellent females to have more offspring.
When women are reluctant to give birth on their own or are physically unable to have children normally, advances in "surrogacy" technology have ignited new hopes for these women to have offspring. Paid "surrogacy" services are controversial and banned in many countries. However, "surrogacy" is a common means of reproduction in the animal farming industry and has made an important contribution to the adequate supply of livestock products.
The core of this "surrogacy" technique is embryo transfer, which is generally the transfer of fertilized eggs or embryos of good females into the womb of "surrogate" females, so that the latter can produce offspring that are not related to them, so as to rapidly expand the population of excellent females. The reproductive technology represented by superovulation, live egg collection, in vitro insemination, embryo transfer, etc., has become an important technology for the rapid breeding of excellent breeding livestock and the cultivation of new breeds.
The first "surrogate mother"
The first recorded "surrogacy" incident dates back to 1890, while the first "surrogate mother" was a Belgian female rabbit. The Englishman Walter Heape detailed this process in the Proceedings of the Royal Society of London.
Born in 1855 in Manchester, the city at the heart of the British Industrial Revolution, Walter Hepp came from a wealthy family and a successful businessman and banker, and in today's parlance, Hepp was an out-and-out "rich second generation". Hepp originally planned to inherit his father's business, and from the beginning of college, he underwent years of business training under his father's arrangement. However, due to health problems, Hepp decided to give up business at the age of 24 and chose scientific research. In 1882, Hepp was hired as an assistant professor of animal morphology at cambridge university and became interested in animal reproduction and breeding.
On 27 April 1890, Hepp removed two fertilized embryos from the womb of an Angolan female rabbit and transferred them to the upper end of the fallopian tube of a Belgian female rabbit. The 7-month-old Belgian female rabbit had just mated with a male rabbit of the same species 3 hours before the embryo transfer. After the "surrogate mother" Belgian mother rabbit completed her pregnancy, she gave birth to six rabbits, four of which were of the same breed as her own, while the other two young rabbits had exactly the same characteristics as the angora rabbit, and had significant differences with the other four Belgian young rabbits in the same fetus, so Hepp was very sure that his first embryo transfer experiment was successful.
However, due to the need for reproducibility in scientific experiments, Hepp conducted several embryo transfer trials in the following years, all of which failed, and it was not until 7 years later that they were successful again, proving that "surrogate" females could be used to breed offspring of another breed. The detailed course of the first embryo transfer trial was also published in the journal Proceedings of the Royal Society of London in 1897. In 1906, Hepp also published his first scientific book, The Breeding Industry, and in the same year he was elected a Fellow of the Royal Society for his exploration of embryo transfer techniques.
In vitro insemination
The reason why embryo transfer technology can be promoted on a large scale is inseparable from in vitro insemination technology. Most reproductive techniques are developed and matured in animals before being applied to assisted reproduction in humans. However, in vitro insemination technology was developed to treat human infertility.
Before introducing the in vitro insemination technique, it is necessary to talk about the invention of artificial insemination technology. Artificial insemination technology was first invented by the famous Russian biologist Ilya Ivanovich Ivanov in 1899. When Studying the reproductive process of animals, Ivanov found that the combination of sperm and egg is the key to animal reproduction, and if properly preserved, sperm can still remain viable for a certain period of time. Initially, Ivanov collected sperm from inside the vagina of a newly mated mare and used it to inseminate other mares and make them pregnant. Later, Ivanov invented methods such as rectal massage and false vagina to collect sperm, and invented methods such as sperm preservation and disinfection, and established a set of artificial insemination techniques. In the decade that followed, Ivanov applied artificial insemination techniques to horses, cattle, sheep, rabbits, chickens, and even dogs and foxes.
In 1922, Ivanov published the results of Russia's large-scale application of artificial insemination technology in animal husbandry production, which caused great concern, and Europe, the United States, Japan and other countries and regions began to study artificial insemination technology. By 1931, nearly 20,000 cows in Russia had been produced using artificial insemination, and countries such as the United States subsequently began to apply this new breeding technology on a large scale. After continuous technical improvement, artificial insemination efficiency has been greatly improved, the cost has been greatly reduced, and artificial insemination technology has become the most extensive breeding technology in animal husbandry production.
It is worth mentioning that Ivanov's pioneering research on artificial insemination techniques is well respected, but his experiments with ape hybridization in the 1920s disgraced science. After using artificial insemination techniques to obtain hybrid offspring such as zebras and donkeys, European bison and domestic cattle, guinea pigs and rabbits, Ivanov began to frantically experiment with ape hybridization. He used chimpanzee semen to vasculate female volunteers, not only failing to obtain the ape hybrid he expected, but also causing the death of some of the volunteers, Ivanov himself was exiled, and after his death was ridiculed as "Frankenstein red".
In vitro insemination techniques by scientists date back to the late 1880s, but it wasn't until the early 1930s that breakthroughs were made in rabbits. In 1934, Gregory Pincus, who was working at Harvard University in the United Kingdom at the time, and colleagues took egg cells from the dark gray female rabbit, inseminated them in vitro, and then transplanted the fertilized eggs into the fallopian tubes of another breed of New Zealand red rabbit, successfully producing 7 young rabbits with dark gray hair.
However, the authenticity of Pincus's "test tube rabbit" as the world's first in vitro insemination animal has been questioned. In 1951, Dr. Colin Austin of Australia and Dr. Zhang Mingjue of the United States independently discovered that sperm acquisition is a necessary condition for egg cell fertilization, that is, the sperm undergoes a series of changes under the action of some amylase in the female reproductive tract secretion, in order to truly obtain the ability to fertilize the egg. Therefore, some people speculate that Pincus mixed eggs and sperm together when breeding "test tube rabbits", and there is no condition for sperm to be able to function, and the egg fertilization process actually occurs after the sperm-egg mixture is injected back into the rabbit's fallopian tubes, not strictly in vitro insemination. In 1959, Dr. Zhang Mingjue of the United States completed the in vitro insemination of domestic rabbits for the first time and obtained a batch of "test tube rabbits". It is generally believed that Dr. Zhang Mingjue's "test tube rabbit" is the world's first in vitro in vitro insemination "test tube animal" without controversy.
In addition to the success of in vitro insemination of small animals such as rabbits, mice, and rats, major breakthroughs in human in vitro insemination have been faster than for large domestic animals such as pigs, cattle, and sheep. On July 25, 1978, British physiologist Robert Edwards and obstetrician and gynecologist Patrick Steptoe collaborated to in vitro insemination of egg cells of patients with tubal occlusion for up to 9 years, and successfully obtained in vitro in vitro insemination of "IVF", which became the most important assisted reproductive technology for the treatment of various infertility disorders, and also laid the foundation for the application of "surrogacy" in humans and livestock. By the end of 2018, more than 8 million IVF babies had been born worldwide. In 2010, Edward was also awarded the Nobel Prize in Physiology or Medicine.
The success of "IVF" not only brings great hope to infertility patients around the world, but also stimulates the research and application of in vitro in vitro in vitro infusion in livestock. In the 1980s, scientists in Japan, the United States and other countries have bred the world's first batch of test-tube cattle, test-tube goats, test-tube pigs, test-tube sheep, and even in vitro inseminated baboons and chimpanzees have also been successful. Animal "surrogacy" technology is also becoming more mature, and its application in animal husbandry production is becoming more in-depth.
The more embryos the better
With the maturity of in vitro insemination technology, embryo transfer technology has become more useful. Unlike human reproductive purposes, livestock breeding techniques are intended to maximize the genetic potential of good breeding stocks. With artificial insemination, the offspring of an excellent breeding bull can be spread all over the world, and the number of offspring can reach thousands or even tens of thousands of heads per year. With in vitro fertilization and embryo transfer, good females can breed more offspring, but only if there are more egg cells.
Female mammals have a gradual decrease in germ cells, with cattle having about 2 million germ cells during the embryonic stage, still about 200,000 germ cells at birth, and only 2500 follicles left by adulthood. Cattle are singletons, with an average of one litter a year. If calculated according to the reproductive efficiency of natural conception, the cow can give birth to more than ten calves in its lifetime.
In order to get more egg cells or embryos, scientists sacrifice three tricks.
The first trick is overovulation + artificial insemination. In a natural estrus cycle, cattle can generally only release one mature egg, but under some gonadotropin stimulation, the ovaries can release multiple eggs at the same time, up to more than fifty oocytes. Beginning around the 1940s, British zoologists discovered that animal ovaries, under the influence of some pituitary extracts, can release multiple eggs that mature. In the early 1950s, researchers at the University of Cambridge in the United Kingdom first used the serum gonadotropin/equine chorionic gonadotropin (PMSG) in cattle to induce hyperovulation in cattle. However, this pregnant horse serum gonadotropin has a long half-life in the body and can have long-term adverse effects on animal health. At the end of the 1950s, researchers at the University of Minnesota began to use follicle-stimulating hormone (FSH) for overovulation, with good results. With the commercialization of follicle-stimulating formulations in the 1970s, this method has also been used today. Combined with artificial insemination, cows can obtain 6 to 7 transferable embryos per over-row, more than 20 transferable embryos can be produced in a year, and according to the calving rate of 50%, more than 10 calves can be obtained, which is equivalent to the production capacity of a cow in the case of natural conception. At present, more than 400,000 bovine embryos are produced by this method every year in the world, most of which are transferred to the "surrogate" cows, which plays a very important role in continuously improving the production performance of the cattle herd.
The second trick is live egg collection + in vitro insemination. Embryo transfer technology, artificial insemination and in vitro insemination technology were all developed from rodents, while live egg collection technology was specifically aimed at sheep, cattle and other livestock, and later applied to human in vitro embryo production. In 1974, scientists at Michigan State University in the United States first tried live egg collection, and with the assistance of laparoscopy, they successfully aspirated 6 oocytes from sheep follicles stimulated by hormones such as follicles. By the end of the 1980s, ultrasound-guided in vitro egg collection technology had developed and became the main live egg collection technology.
The combination of live egg harvesting and in vitro insemination has made in vitro embryo production vigorously developed. Live egg harvesting has some distinct advantages over the technique of hyperovulation + in vivo insemination. For example, live egg harvesting can obtain 10 to 100 oocytes each time, and each female animal can breed 50 offspring per year, which is more than 5 times the number of offspring bred by the hyperovulation technique; Moreover, these oocytes can be combined with the semen of different bulls, maintaining the genetic diversity of the herd, and the sperm used in each embryo collected for superovulation are generally from the same bull.
At present, live egg collection + in vitro insemination + in vitro embryo maturation + embryo transfer has become an increasingly important livestock breeding technology. According to 2018 data from the International Association for Embryo Technology, more than 1.5 million livestock embryos are produced worldwide, of which 96.7% come from cattle. Of these embryos, more than 1 million are in vitro inseminated.
"Super Father"
A breeding bull can collect tens of thousands or even hundreds of thousands of doses of semen a year, and each cow can obtain more than 100 in vitro embryos a year through live egg collection and in vitro insemination technology, and more than 20 in vivo embryos obtained through overovulation. A large number of semen and embryos may not be used up immediately, only when the cryopreservation technology develops and matures, the animal "surrogacy" technology can really be promoted on a large scale around the world, and excellent breeding stocks can also branch out in all corners of the world.
In the 1930s, scientists began to try to use cryopreservation cells, but cryopreserved sperm destroyed cell membranes because of ice crystals formed inside and outside cells, resulting in frozen sperm unable to thaw and resurrect, let alone rejuvenate. In 1949, Polge et al. of the National Institute of Medicine published a short, one-page paper in the journal Nature, in which the team found that glycerol as a semen dilution could protect a variety of semen, including human semen, and that poultry semen frozen for 10 weeks at -79 °C under the protection of more than 20% glycerol semen dilution could be completely rejuvenated and formed chicken embryos through in vitro insemination. To date, the study by British scientists has been cited more than 2,300 times and has become the cornerstone of the research result of cryopreservation of semen and embryos in humans and other animals.
In 1950, British scientists used frozen semen for the first time to obtain the first calf. In the following years, scientists continued to improve cryopreservation protectors, freeze and thaw procedures, and promoted the rapid application of artificial insemination technology in herds, making artificial insemination increasingly the most conventional breeding technology. At present, the utilization rate of frozen semen in dairy cows in the United States and other countries can reach more than 90%. Some breeding bulls have also become "super fathers", with hundreds of thousands or even hundreds of thousands of "children" around the world.
A breeding bull called "Toy Story" became the breeding bull with the largest number of children. "Toy Story" was born in May 2001 and takes its name from the Hollywood animated film Toy Story. The breeding bull began collecting sperm around the age of 1, and by his death in October 2014, it had produced more than 2.4 million doses of semen in its lifetime, and had produced a staggering 500,000 offspring, 25 times the average number of offspring of the average breeding bull, and its offspring were spread to more than fifty countries around the world. All of the "Toy Story" is so successful, on the one hand, because it is very strong in itself, and its ability to produce sperm is very strong; On the other hand, because its semen fertilization rate and calving rate are very high, and female offspring have the characteristics of physical fitness and high milk production, they are very popular. In 2009, one of its "daughters" was auctioned off for $340,000.
Embryo freezing is much later than semen freezing techniques. In 1971, Whittingham of the University Of Humanities Laboratory in Cambridge, England, first reported in the journal Nature that he had successfully used dry ice to preserve mouse embryos of the 8-cell stage, which could continue to develop normally after thawing most of the mouse embryos preserved at -79 °C. The following year, Whitingham et al. further continued the mouse embryo freezing experiment in -196 °C and -269 °C liquid nitrogen, this time they froze about 2500 embryos, after thawing about 1000 embryos were resurrected, they were transferred to the "surrogate" female mouse, about 65% of the female mice were successfully pregnant, of which 40% of the pregnant mother mice successfully gave birth to healthy mice. The study, published in the form of a cover story in the journal Science, greatly stimulated the enthusiasm of scientists to study the technology of cryogenic freezing of livestock embryos.
In 1973, Ian Wilmut, a developmentist at the Rosslyn Institute in the United Kingdom, and colleagues thawed cryopreserved embryos and transferred them to a "surrogate" cow, resulting in a frozen embryo calf, named Frosty. It is worth mentioning that the research team led by Wilmut shocked the world in 1996 by breeding the world's first somatic cell-cloned livestock, dolly sheep.
Relative to semen and embryos, people did not attach great importance to the cryopreservation of oocytes, because there were fewer oocytes at that time, and in vitro insemination techniques were not very mature. However, by the end of the 1970s and early 1980s, with the increasing maturity of live egg collection technology and in vitro insemination technology, the cryopreservation technology of oocytes also began to develop, and the preservation of oocytes in animals such as rats, hamsters, rabbits, monkeys and so on was successful, and then the human oocyte preservation technology was also becoming more and more mature. As oocyte and embryo cryopreservation techniques mature, "surrogacy" techniques are becoming increasingly important in the livestock breeding process.
Southern Weekend Contributing Writer Tombo