Effects Of Different Doses Of Estrogen On The Repair Of Rat Endometrial Injury

Objective Intrauterine adhesion(IUA) is a common gynecological disease which affects the physical and mental health of women of childbearing age. It has become one of the common causes of female infertility. Among the many IUA formation factors, the most common cause is intrauterine manipulation. At present, the formation mechanism of IUA is still unclear, and there is no effective treatment. Preventing IUA after uterine cavity operation especially for curettage has important significance. Prevention IUA and IUA formation again has become a hot research topic in the academic. Although estrogen is widely used in induced abortion, but its effect on the prevention of IUA formation and the use of dosage and so on are still controversial. Under the restriction of ethical factors, it is necessary to study the effect of estrogen on the prevention of intrauterine adhesion on the basis of establishing an experimental animal model which is stable and ideal. Our research group has successfully established a stable animal model of intrauterine adhesions in rats, which can provide a good platform for the prevention of IUA related research. This research is expected based on this animal experimental model to blocking the synthesis of estrogen in the body by aromatase inhibitor------Letrozole), then add different doses of exogenous estrogen. The effect of estrogen on uterine cavity adhesion formation were investigated, including estrogen intervention on 7 days after injured, and the long-term endometrial receptivity function.Method(1) Short-term effect observation of different doses of estrogen’ interference in intrauterine adhesion of rats: selected the Wistar rats in estrus through conventional vaginal smear and random Ly divided them into 5 groups. In addition to normal Control group(group C), the rest 4 groups all adopted self-made miniature spatula to simulate mechanical dilatation and curettage, and were treated with injury of uterus on the left side, while the right side was not treated. According to the needs of different observation, the rest four groups were divided into Damage group(group D), Damage +Letrozole group(group DL), Damage+Letrozole+10μg E2 group(group DL-10) and Damage+Letrozole+100μg E2 group(group DL-100). Collected serum of rats in various groups for testing before the operation, and 3 and 5 days after operation and before killing. All the rats were killed by being broken neck on 4 o’clock in the afternoon 7days after operation, collected materials immediately and collected uterus specimens.The expression of HE staining and correlation factors of immunohistochemical examination tissue repair in the endometrium after routine paraffin embedding and section.(2) Long-term effect observation of different doses of estrogens’ prevention of intrauterine adhesion of rats: random Ly divided the Wistar rats in estrus into 4 groups,respectively were normal Control group(group C), Damage group(group D), Damage+ 10μg E2 group(group D-10) and Damage +100μg E2 group(group D-100). Injury and estrogen intervention were as above. Let female rats mate with male rats after 21 days of estrogen intervention, and killed for collecting materials after rats being pregnant for5.5 days and 7 days. The expression of treating with HE staining and immunohistochemical examination receptivity correlation in the endometrium after routine paraffin embedding and section.Result(1) Based on intrauterine adhesion model of rats, the experiment intervened model by using aromatase inhibitors and exogenous estrogen adding. Observed from aspects such as correlation factors of HE morphological staining and adhesion,correlation factors of angiogenesis, correlation factors of inflammatory and generated cells, etc., with the increase in the level of estrogen in the body, the area of endometrial fibrosis had narrowed and had statistical differences(P <.05). But in the environment of high estrogen, the endometrial glandular epithelium of rats showed different degrees of squamous metaplasia.(2) The effect observation of endometrium damage of rats on endometrial receptivity after being given with different doses of estrogen intervention,C and D-10 groups had rich glands and many parenchymal cells, while the number of glands of D and D-100 had significantly reduced, parenchymal cells reduced and fibrotic area was larger. Compared various damage groups with group C, the expression quantity of endometrial αvβ3 and LIF decreased significantly(P<.05); compared group D-10 with group D, group D-100, the expression quantity of αvβ3 and LIF increased significantly(P <.05); compared group D-100 with group D, expression quantity of αvβ3 was equivalent(P>.05),while expression quantity of LIF decreased(P<.05). Compared with group C and self-control side of various groups, the number of implantation sites of damage side of various damage groups reduced significantly(P<.05); compared between various damage groups, the number of implantation of group D-10 increased slightly than those in group D and group D-100, but had no significant difference; compared group D-100 with group D, they had equivalent number of implantation and had no significant difference.Conclusion(1) Prompt of estrogen can reduce the incidence of uterine adhesion and fibrosis to some extent, but the use of high estrogen will bring about high risks and side effects.(2) Estrogen addition can promote endometrial repair and improve the function of endometrial receptivity to a certain extent, 10μg dose(equivalent to physiological level of rats) has the best effect, and large dose of estradiol may lead to the decline in endometrial receptivity.