Method for producing animal model of preterm birth and animal model of preterm birth produced by the method

#This application is a § 371 national stage entry of International Application No. PCT/KR2017/004148, filed on Apr. 18, 2017, which claims priority to South Korean Patent Application No. 10-2016-0055878, filed on May 6, 2016, and South Korean Patent Application No. 10-2017-0047866, filed on Apr. 13, 2017, the entire contents of which are incorporated herein by reference.

#The present invention relates to a method for producing an animal model of preterm birth and an animal model of preterm birth produced by the method.

#Preterm birth refers to the birth of a baby between 20 weeks and 37 weeks of pregnancy. Preterm birth accounts for approximately 12% of all pregnancies and is the most common cause of neonatal morbidity and mortality around the world. According to a US report, the socioeconomic cost of preterm birth was estimated to be $2.6 trillion in 2005.

#FIG. 1 shows photographic images of cervical excision performed in Example 1.

#FIG. 2 shows the anatomical locations of the uterus and cervix of a rodent.

#FIG. 3 is a model showing cervical injury and loss.

#Thus, the present inventor has earnestly and intensively conducted research to develop an animal model whose preterm birth is induced at an accurate time point while maintaining a very low mortality rate until preterm birth, and as a result, has succeeded in developing an improved method for producing an animal model of preterm birth. The present invention has been accomplished based on this finding.

#Specifically, a method for producing an animal model of preterm birth according to the present invention includes 1) excising the cervix of a mammal through the vagina of the mammal, 2) allowing the mammal to recover, 3) making the mammal pregnant, and 4) injecting lipopolysaccharide (LPS) intrauterinely or intraperitoneally into the mammal.

#In step 1), the cervix of a mammal is excised through the vagina of the mammal. Preferably, the cervix is excised without cutting the abdomen open. For example, the cervix may be excised through direct access to the vagina. The cervix may be excised with a suitable tool such as a scalpel. Preferably, the entrance of the vagina is opened for access to the vagina. For this opening, the vaginal wall is firmly held with forceps. The opening of the entrance of the vagina is to secure a sufficient field of view, allowing direct excision of the cervix. In contrast, cervical excision by laparotomy may lead to a high mortality rate and may require a long recovery time. Therefore, the direct cervical excision in step 1) does not lead to a high mortality rate and shortens the time needed for recovery. As a result of the direct cervical excision, resistance to an increasing intrauterine pressure is reduced, resulting in a high probability of preterm birth.