【発明の詳細な説明】[Detailed description of the invention]
〔産業上の利用分野〕
本発明は、FSH（卵胞刺激ホルモン Follicle
Stimulating Hormone）による効率的な牛の双
子生産技術に関するものである。
〔従来の技術〕
肉用牛生産のためのコストの大部分を占めるの
は、繁殖雌牛の飼育管理費である。したがつて、
１頭の雌牛から２頭の産子を得ることができれ
ば、１頭の産子を得るよりも経済効率は極めて高
くなる。そこで、肉資源の経済的増産の手段とし
て牛の双子生産の技術が検討されてきた。
従来、牛の双子生産技術には、(1)受精卵２卵移
植方式、(2)追い移植方式（人工授精した後受精卵
を移植）及び(3)ホルモン低単位投与方式などがあ
る。
受精卵２卵移植方式は、後述する方法で採取し
た受精卵２個を、借り腹牛、すなわち受卵牛の子
宮に移植して妊娠させる方法である。受精卵の採
取には、能力の高い特定の雌牛、すなわち供卵牛
の黄体期に総量約40mg（又はAU）のFSHを１日
２回ずつ４〜５日間に分割注射することにより卵
巣に多数の卵胞を発育させ、FSH初回投与から
48時間ないし72時間経過後に黄体退行作用のある
プロスタグランデインF2αを注射して誘起された
人工発情時に能力の高い特定の雄牛の精子を授精
させ、約１週間後に子宮を洗浄して受精卵を採取
し、検査、選別を行つて良い受精卵、約数個を特
殊設備で保存する。
追い移植方式は、受卵牛の自然発情時に人工授
精を行い、約１週間後に、更に別の供卵牛から採
取した受精卵１個を移植して双子生産を図る方法
である。
他方、ホルモン投与方式は、通常１発情時に１
個排卵する動物である雌牛にホルモンを投与して
複数の排卵を誘起し、多胎妊娠させる方法であ
り、前述の２方法に比してホルモン投与以外には
特殊処理がなく、手間がかからずコストも少なく
て済む利点がある。
その具体的な方法としては、性周期の黄体期に
ある雌牛に対し、PMSG（妊馬血清性性腺刺激ホ
ルモン）の注射又はFSHを１日２回ずつ２〜３
日間分割注射を行つて卵胞を発育させ、ホルモン
初回投与後24〜48時間後に黄体退行を促進させる
ためプロスタグランデインF2αを注射し、誘起さ
れた発情時に１〜２回の授精を行つて受胎・分娩
させる方法である。
〔発明が解決しようとする課題〕
しかしながら、移植方式は受精卵のコストが高
く、その作業には多くの手間を要し、特殊な技術
と設備を必要とするため、現実には実施すること
が困難な面があつた。
また、ホルモン投与方式は、ホルモン投与によ
り１〜８個の排卵が誘発され、排卵数の増加に比
例して受胎率も向上し、多胎率（双子以上の受胎
頭数／受胎頭数）40〜80％の成績が得られたが、
３子以上の受胎例では物理的或いは生理的な原因
で妊娠牛の子宮は妊娠を継続できず、流産の発生
率が異常に高くなるという問題があつた。双子の
受胎例では流産するものが少ないので、ホルモン
の投与方法の調整により排卵数を２個前後に制御
する方法が検討されたが、ホルモン投与による排
卵数の制御は困難でこの方式による双子生産技術
は疑問視されていた。
〔課題解決の手段〕
本発明は上記課題を解決することを目的とし、
その構成は、総量６〜10mg（又はAU）のFSH
を、24時間間隔で２回に分けて投与することを特
徴とする。
本発明に使用するFSHは家畜、例えば豚、牛、
羊、馬などの下垂体前葉から抽出されるものであ
る。通常は少量のLH（黄体形成ホルモン）を含
有しているが、本発明におけるFSHとはLH含有
量の多いものから、精製されLHを極く微量にし
か含有しないものまですべてを包含する。
ホルモンの投与方法は、性周期の黄体期にある
雌牛に対しFSHを１日１回ずつ２日注射して卵
巣の卵胞発育を促進させる。同一時間、すなわち
24時間後に投与することが好ましいが、牧場にお
ける現実の牛の管理上、常に正確に24時間間隔を
守ることは困難で、例えば第１日目に午前中に投
与したが、第２日目には獣医師或いは作業の都合
上、午後に投与しなければならないような事態が
発生しがちである。しかしながら、現実の作業上
常識的に発生しがちな時間的ずれは差支えなく、
同等の効果が得られる。通常FSHの第１回投与
の24時間後に、黄体退行因子のプロスタグランデ
インF2αを注射し、発情が誘起されたら１〜２回
の授精を行う。
FSHの力価は、FSHアーマー標準品を用いて
ラツト卵巣重量増加法によつて測定され、mg又は
AUで表わされる。
FSHの総投与量は６〜10mg（又はAU）であ
る。６mg（又はAU）未満では２個以上排卵する
割合が少なく、したがつて双子率が低いので好ま
しくない。10mg（又はAU）を越えると、発情
率、受胎率及び双子率は高くなるが、３〜５個排
卵する割合が高くなり、流産発生率が高くなるの
で好ましくない。
FSHは総投与量６〜10mg（又はAU）を２日に
分けて投与する。FSH6〜10mg（又はAU）の１
回投与では排卵数が増加せず好ましくない。３回
以上投与してもその手間にふさわしい効果がな
く、投与回数の増加は省力化の点で好ましくな
い。
〔作用〕
本発明は、雌牛の多胎による流産を避けながら
可及的に多くの双子を生産させるものである。そ
のためにはFSHの投与量を総量６〜10mg（又は
AU）とし、２日に分けて投与することにより、
平均排卵数を1.4〜1.6程度に調整し双子率を20〜
30％に調整するものである。
〔実施例〕
以下、実施例により本発明を具体的に説明す
る。
実施例 １
繁殖用雌牛73頭に対し、黄体期に60〜10mg（又
はAU）のFSH（デンカ製薬(株)製、商品名アント
リン）を２日に分けて24時間間隔で注射投与し
た。初日には４〜６mg（又はAU）を投与した。
第１回投与の24時間後の第２回投与の時にプロス
タグランデインF2α―Ａ（クーパーズアニマルヘ
ルス(株)製、商品名エストラメイト）を500μｇ投
与した。発情が誘起された時１〜２回の授精を行
つた。その結果双子率は23％、流産率は３％、産
子率（産子数／分娩頭数）126％であつた。これ
らの条件及び結果を第１表に記載する。
比較例 １ないし比較例 ６
繁殖用雌牛57頭を用い、FSHの投与を行わな
い無処置の自然分娩の場合を比較例１とした。こ
の場合は双子発生は全例に認められなかつた。
総量３〜５mg（又はAU）のFSHを実施例１と
同様に投与した場合を比較例２とし、総量11〜15
mg（又はAU）のFSHを実施例１と同様に投与し
た場合を比較例３とした。比較例２の場合には、
排卵数は平均1.1個で双子の発生は全例で認めら
れなかつた。比較例３の場合は、発情率、受胎率
が高く排卵数は平均2.3個で双子率も40％と高か
つたが、３〜５個排卵する例も多く、流産発生率
は29％と異常に高かつた。以上の結果を第１表に
併記した。
FSH3〜５mg（又はAU）を12時間間隔で４回
投与した場合を比較例４とし、FSH6〜10mg（又
はAU）を12時間間隔で４〜６回投与した場合を
比較例５とし、FSH11〜15mg（又はAU）を12時
間間隔で４〜６回投与した場合を比較例６とし
た。比較例４では排卵数は1.2個で双子の発生は
全例共認められなかつた。比較例５では発情発現
も良好で排卵数は平均1.6個で、双子率は23％で
あり、流産発生率は４％と低かつた。比較例６で
は、発情率、受胎率共に高く、排卵数は平均2.5
と多くなつた結果、双子率は40％と向上したが、
３〜５個排卵する例も多く、流産発生率は44％と
異常に高かつた。以上の結果を第１表に併記し
た。
[Industrial Application Field] The present invention is directed to FSH (Follicle Stimulating Hormone Follicle
This study concerns an efficient cow twin production technique using Stimulating Hormone. [Prior Art] The cost of raising and managing breeding cows accounts for most of the costs for producing beef cattle. Therefore,
If you can get two calves from one cow, it will be much more economically efficient than producing one calf. Therefore, the technology of cow twin production has been considered as a means of economically increasing the production of meat resources. Conventional cow twin production techniques include (1) two fertilized eggs transplantation method, (2) follow-up transplantation method (transplantation of fertilized eggs after artificial insemination), and (3) low-unit hormone administration method. The two-fertilized egg transplantation method is a method in which two fertilized eggs collected by the method described below are transplanted into the uterus of a borrowed cow, that is, a recipient cow, to cause pregnancy. To collect fertilized eggs, a total amount of approximately 40 mg (or AU) of FSH is injected into the ovaries twice a day for 4 to 5 days during the luteal phase of a specific high-capacity cow, i.e., a donor cow. from the first administration of FSH.
After 48 to 72 hours, prostaglandin F 2 α, which has a luteal degeneration effect, is injected to induce artificial estrus, and the sperm of a specific bull with high ability is inseminated, and about a week later, the uterus is washed. The fertilized eggs are collected, inspected and sorted, and the few fertilized eggs that are good are stored in special equipment. The follow-up transplant method is a method in which artificial insemination is performed when a recipient cow is in natural heat, and about one week later, a single fertilized egg collected from another donor cow is transferred to produce twins. On the other hand, the hormone administration method is usually 1 at each estrus.
This is a method of administering hormones to cows, which are animals that ovulate individually, to induce multiple ovulations and resulting in multiple pregnancies.Compared to the two methods mentioned above, there is no special treatment other than hormone administration, and it requires less effort. It has the advantage of being less costly. The specific method is to inject PMSG (pregnant mare serum gonadotropin) or FSH 2 to 3 times a day to cows in the luteal phase of their estrous cycle.
Daily divided injections are performed to develop follicles, 24 to 48 hours after the first hormone administration, prostaglandin F 2 α is injected to promote corpus luteum regression, and one or two inseminations are performed when estrus is induced. This is a method of conception and delivery. [Problems to be solved by the invention] However, the transplant method is difficult to implement in reality because the cost of fertilized eggs is high, the work requires a lot of effort, and special technology and equipment are required. There were some difficult aspects. In addition, with the hormone administration method, 1 to 8 ovulations are induced by hormone administration, and the pregnancy rate improves in proportion to the increase in the number of ovulations. The results were obtained, but
In cases where three or more offspring are conceived, the uterus of the pregnant cow is unable to continue the pregnancy due to physical or physiological reasons, resulting in an abnormally high incidence of miscarriage. Since few cases of twin conception result in miscarriage, a method of controlling the number of ovulations to around two by adjusting the method of administering hormones was considered, but it was difficult to control the number of ovulations by administering hormones, and this method was not used to produce twins. The technology was questionable. [Means for solving the problems] The present invention aims to solve the above problems,
Its composition is a total amount of 6-10 mg (or AU) of FSH
It is characterized by being administered in two doses at 24-hour intervals. The FSH used in the present invention is a livestock animal, such as a pig or a cow.
It is extracted from the anterior pituitary gland of sheep, horses, etc. Normally, it contains a small amount of LH (luteinizing hormone), but in the present invention, FSH includes everything from those with a high LH content to those that are purified and contain only a trace amount of LH. The hormone is administered to cows in the luteal phase of their estrous cycle by injecting FSH once a day for two days to stimulate follicular development in the ovaries. same time, i.e.
It is preferable to administer the drug 24 hours later, but due to the actual management of cattle on farms, it is difficult to always maintain accurate 24-hour intervals. For example, if the drug is administered in the morning on the first day, but on the second day However, due to the veterinarian's or work schedule, situations tend to occur where the administration has to be done in the afternoon. However, there is no problem with the time lag that commonly occurs in actual work.
The same effect can be obtained. Usually, 24 hours after the first administration of FSH, prostaglandin F 2 α, a luteal degeneration factor, is injected, and once estrus is induced, one or two inseminations are performed. FSH titer was determined by the rat ovary weight gain method using FSH Armor standard, mg or
Represented in AU. The total dose of FSH is 6-10 mg (or AU). If it is less than 6 mg (or AU), the rate of ovulation of two or more eggs is low, and therefore the twin rate is low, which is not preferable. If it exceeds 10 mg (or AU), the estrus rate, conception rate, and twin rate will increase, but the rate of ovulation of 3 to 5 eggs will increase, and the miscarriage rate will increase, which is not preferable. FSH is administered at a total dose of 6-10 mg (or AU) divided into 2 days. 1 of FSH6-10mg (or AU)
Multiple administrations do not increase the number of ovulations and are not preferred. Even if the drug is administered three or more times, there is no effect that is worth the effort, and increasing the number of doses is not preferable from the point of view of saving labor. [Operation] The present invention allows cows to produce as many twins as possible while avoiding miscarriages due to multiple pregnancies. For this purpose, the total dose of FSH should be 6 to 10 mg (or
AU) and by administering it in two days,
Adjust the average number of ovulation to about 1.4 to 1.6 and reduce the twin rate to 20 to 1.6.
This will be adjusted to 30%. [Example] Hereinafter, the present invention will be specifically explained with reference to Examples. Example 1 During the luteal phase, 60 to 10 mg (or AU) of FSH (manufactured by Denka Pharmaceutical Co., Ltd., trade name Antolin) was injected at 24-hour intervals over two days to 73 breeding cows. 4-6 mg (or AU) was administered on the first day.
At the time of the second administration 24 hours after the first administration, 500 μg of prostaglandin F 2 α-A (manufactured by Cooper's Animal Health Co., Ltd., trade name: Estramate) was administered. One or two inseminations were performed when estrus was induced. As a result, the twin rate was 23%, the miscarriage rate was 3%, and the litter rate (number of offspring/number of calves) was 126%. These conditions and results are listed in Table 1. Comparative Example 1 to Comparative Example 6 Comparative Example 1 was a case in which 57 breeding cows were used and natural calving was performed without administration of FSH. In this case, twin occurrence was not observed in all cases. Comparative Example 2 is a case in which a total amount of 3 to 5 mg (or AU) of FSH was administered in the same manner as in Example 1, and the total amount was 11 to 15 mg.
Comparative Example 3 was a case in which mg (or AU) of FSH was administered in the same manner as in Example 1. In the case of Comparative Example 2,
The average number of ovulations was 1.1, and no twins were observed in any case. In the case of Comparative Example 3, the estrus rate and conception rate were high, the average number of ovulations was 2.3, and the twin rate was high at 40%, but there were many cases where 3 to 5 ovulations occurred, and the miscarriage rate was abnormal at 29%. It was expensive. The above results are also listed in Table 1. Comparative Example 4 is a case in which 3 to 5 mg of FSH (or AU) was administered 4 times at 12 hour intervals, Comparative Example 5 is a case in which 6 to 10 mg of FSH (or AU) was administered 4 to 6 times at 12 hour intervals, and FSH11 to Comparative Example 6 was a case in which 15 mg (or AU) was administered 4 to 6 times at 12 hour intervals. In Comparative Example 4, the number of ovulations was 1.2, and no twins were observed in any case. In Comparative Example 5, the onset of estrus was good, the average number of ovulations was 1.6, the twin rate was 23%, and the miscarriage rate was low at 4%. In Comparative Example 6, both the estrus rate and conception rate were high, and the average number of ovulations was 2.5.
As a result, the twin rate increased to 40%,
Many women ovulated between 3 and 5 eggs, and the miscarriage rate was an abnormally high 44%. The above results are also listed in Table 1.
【表】
総量として６〜10mg（又はAU）のFSHを２日
以上にわたつて投与する実施例１と比較例５を用
いると牛の双子生産を流産率を低く行うことがで
きるが、両者を比較すると比較例５の方法は獣医
師の往診回数と注射回数が多く煩雑であり、その
ためのコストも高くなるので、実施例１の方法が
省力的かつ実用的である。
〔発明の効果〕
本発明は、特殊な設備及び技術を要することな
く、FSHのより少ない投与量、及び投与回数に
より投与のコスト及び手間を省略し、流産率を低
下させ、双子率を向上し、産業上きわめて有利な
方法である。[Table] Using Example 1 and Comparative Example 5, in which a total amount of 6 to 10 mg (or AU) of FSH is administered over 2 days or more, cow twin production can be performed with a low abortion rate. In comparison, the method of Comparative Example 5 is complicated and requires a large number of veterinarian visits and injections, which also increases the cost, so the method of Example 1 is labor-saving and practical. [Effects of the Invention] The present invention reduces the cost and labor of administering FSH by reducing the amount of FSH administered and the number of times it is administered, reducing the miscarriage rate and improving the twin rate, without requiring special equipment or techniques. This is an industrially extremely advantageous method.