CROSS-REFERENCE TO RELATED APPLICATIONS

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.

TECHNICAL FIELD

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.

BACKGROUND ART

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.

Preterm birth is caused by various factors. Infection is currently known as the most important mechanism of preterm birth but such an inflammatory response is not always involved in the mechanism of inducing preterm birth. This fact makes it difficult to develop clear preventive and therapeutic approaches for preterm birth. Whatever its causes, preterm birth involves cervical maturation and dilatation. The clinical probability of preterm birth increases markedly in women who have undergone cervical conization or miscarriage and as a result whose cervix has been removed or injured.

As such, the role of the cervix in association with preterm birth is very important. Since damage to the cervical structure or tissue increases the risk of preterm birth, there is a need for a trial to thoroughly elucidate the relationship between preterm birth and the cervix to lower the probability of preterm birth. Despite this trial, studies remain in the early stages.

The cervix is anatomically located at the entrance of the uterus and is connected to the vagina. The cervix is a rigid structure that remains closed before changes associated with parturition occur. The cervix is a fibrous, connective tissue consisting of an extracellular matrix composed of type I and II collagens, elastin, and proteoglycans, smooth muscles, and blood vessels. There is a need to scrutinize the structure or tissue of the cervix and elucidate the relationship between the cervix and preterm birth in order to provide animal models for the purpose of further lowering the probability of preterm birth.

On the other hand, rodent models of preterm birth are known whose preterm birth is induced by injecting lipopolysaccharide between two gestational sacs near the cervix at day 15-17 of gestation. However, these animal models cannot be effectively utilized because the injection of lipopolysaccharide leads to a decrease in preterm birth yield and an excessive increase in mortality.

In this connection, experimental rabbit models whose preterm birth is induced by intrauterine infection after injection of bacteria into the uteri of pregnant rabbits through a hysteroscope are disclosed in Obstetrics & Gynecology Science, Vol. 38, No. 10 (1995), pp. 1819-1828 (“Non-Patent Document 1”)). However, the experimental procedure is complicated, the animal models are expensive to purchase and require high management costs, and it takes a very long time for symptoms to be reproduced. For these reasons, studies on the mechanism of preterm birth and the development of therapies for preterm birth using the animal models are limited.

DETAILED DESCRIPTION OF THE INVENTION

Problems to be Solved by the Invention

The present invention has been made in an effort to solve the above-described problems, and it is an object of the present invention to provide a method for producing an animal model of preterm birth that appropriately reflects a situation in which preterm birth is induced by damage to the cervix.

Means for Solving the Problems

A method for producing an animal model of preterm birth according to one feature of 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.

An animal model of preterm birth according to another feature of the present invention is produced by the method.

Effects of the Invention

The method of the present invention appropriately reflects a situation in which preterm birth is induced by damage to the cervix and is effective in providing an animal model of preterm birth based on this situation. In addition, the animal model of the present invention can be used to control and predict the time when preterm birth occurs. The animal model of the present invention can provide premature neonates.

The animal model of the present invention can reproduce a situation close to actual preterm birth induced by injury, damage or loss of the cervix compared to existing models. The animal model of the present invention can reproduce symptoms similar to those of actual patients, thus being suitable for use as a preclinical experimental model. Therefore, the animal model of the present invention is expected to greatly contribute to studies on preterm birth.

In addition, the animal model of the present invention can be effectively applied to the development of biomaterials for the investigation of the mechanism of preterm birth and therapies for preterm birth. The mortality rate of premature neonates born from the animal model of the present invention is low and the premature neonates are immature. Therefore, the animal model of the present invention can be effectively applied to studies on complications of premature neonates.

