阅读说明：本技术 流产中的特征性代谢物 (Metabolites characteristic of abortion ) 是由 T·C·陈 C·W·古 N·S·陈 Z·W·陈 于 2018-04-30 设计创作，主要内容包括：本文公开了鉴定受试者的流产风险的方法,该方法包括检测并测量获自所述受试者的样品中至少一种代谢物的浓度。具体地,血清或尿液样品中四氢可的松浓度的增加以及丙酰基肉碱、异戊酰基肉碱、3-甲基戊二酰基肉碱、己酰基肉碱或3α,20α-二羟基-5β-孕烷-3-葡糖苷酸浓度的降低与早期妊娠中的自然流产相关。本文还公开了用于确定受试者的流产风险的试剂盒。(Specifically, an increase in the concentration of tetrahydrocortisone and a decrease in the concentration of propionyl carnitine, isovaleryl carnitine, 3-methylglutaryl carnitine, hexanoyl carnitine or 3 α,20 α -dihydroxy-5 β -pregnane-3-glucuronide in a serum or urine sample is associated with spontaneous abortion in early pregnancy.)

1. A method of identifying a risk of abortion, the method comprising detecting and measuring the concentration of at least one metabolite in a sample obtained from a subject, wherein the absence or presence of said metabolite compared to a control group identifies an increased risk of abortion, wherein said metabolite is selected from the group consisting of tetrahydrocortisone, propionyl carnitine, isovaleryl carnitine, 3-methylglutaryl carnitine, hexanoyl carnitine and 3 α,20 α -dihydroxy-5 β -pregnan-3-glucuronide.

2. A method of identifying a risk of miscarriage, the method comprising:

measuring the concentration of at least one metabolite in a sample obtained from the subject; and

comparing the concentration of the at least one metabolite with the concentration of the corresponding metabolite in the control group;

wherein the metabolite is selected from the group consisting of tetrahydrocortisone, propionyl carnitine, isovaleryl carnitine, 3-methylglutaryl carnitine, hexanoyl carnitine and 3 α,20 α -dihydroxy-5 β -pregnan-3-glucuronide and combinations thereof.

3. The method of any one of the preceding claims, wherein an increase or decrease in the concentration measurement or the absence or presence of a metabolite, as compared to the control group, identifies an increased risk of miscarriage.

4. The method of any one of the preceding claims, wherein the control group consists of subjects who underwent term labor.

5. The method of any one of the preceding claims, wherein the method comprises measuring at least two, at least three, at least four metabolites, at least five metabolites, or six metabolites.

6. The method of any one of the preceding claims, wherein the metabolites are tetrahydrocortisone, propionyl carnitine, isovaleryl carnitine, 3-methylglutaryl carnitine, caproyl carnitine and 3 α,20 α -dihydroxy-5 β -pregnan-3-glucuronide.

7. The method of any one of the preceding claims, wherein a decrease in 3 α,20 α -dihydroxy-5 β -pregnan-3-glucuronide is indicative of an increased risk of abortion.

8. The method of claim 7, wherein the decrease in 3 α,20 α -dihydroxy-5 β -pregnan-3-glucuronide compared to a control is a decrease (-0.30) of a fold change in concentration of at least 0.30 compared to a control.

9. The method of any one of the preceding claims, wherein an increase in tetrahydrocortisone is indicative of an increased risk of abortion.

10. The method of claim 9, wherein the increase in tetrahydrocortisone compared to the control is an increase in the concentration compared to the control by a fold change of at least 0.40.

11. The method of any one of the preceding claims, wherein a decrease in propionyl carnitine is indicative of an increased risk of abortion.

12. The method of claim 11, wherein the reduction in propionyl carnitine compared to a control is a reduction (-0.41) of a fold change in concentration of at least 0.41 compared to a control.

13. The method of any one of the preceding claims, wherein a decrease in isovaleryl carnitine is indicative of an increased risk of abortion.

14. The method of claim 13, wherein the reduction in isovalerylcarnitine compared to a control is a reduction (-0.32) of a fold change in concentration of at least 0.32 compared to a control.

15. The method of any one of the preceding claims, wherein a decrease in 3-methylglutaryl carnitine is indicative of an increased risk of abortion.

16. The method of claim 15, wherein the reduction of 3-methylglutaryl carnitine compared to a control is a reduction (-0.59) of a fold change of at least 0.59 in concentration compared to a control.

17. The method of any one of the preceding claims, wherein an increase in caproyl carnitine is indicative of an increased risk of abortion.

18. The method of claim 17, wherein the increase in caproyl carnitine compared to a control is an increase in the fold-change in concentration of at least 0.38 compared to a control.

19. The method of any one of the preceding claims, wherein the miscarriage is selected from the group consisting of: spontaneous abortion, early abortion, mid-abortion, withered eggs and protracted abortion.

20. The method of any one of the preceding claims, wherein the metabolite is detected using a method selected from the group consisting of: chromatography, antibody-based assays, mass spectrometry, immunoprecipitation, and combinations thereof.

21. The method of any one of the preceding claims, wherein the sample is a serum or urine sample.

22. The method according to any one of the preceding claims, wherein dydrogesterone is administered to the subject if the subject is identified as being at risk of miscarriage.

23. A kit for identifying risk of miscarriage according to the method as claimed in claims 1 to 21.

24. The kit of claim 23, wherein the kit is a kit selected from the group consisting of: ELISA kit, test strip kit and microchip test kit.

25. The kit according to claim 23, wherein the kit comprises one metabolite standard for each metabolite as described in any one of claims 1 to 21.

Technical Field

The present invention relates generally to the field of molecular biology. In particular, the invention relates to the use of biomarkers for detecting miscarriage and identifying women at risk of miscarriage.

Background

Threatened abortion (threatened miscarriage) is the most common gynecological emergency, occurring in about 20% of pregnant women. About one-fourth of these women continue to develop spontaneous abortion, yet the cause of abortion remains elusive. In order to identify possible biomarkers and novel therapeutic targets, many studies have been conducted to elucidate the pathways leading to abortion.

To date, no studies have been conducted on metabolites of urine associated with spontaneous abortion. Since current prenatal care does not accurately identify women at high risk of spontaneous abortion with sufficient accuracy, further understanding of the underlying causes is needed to better predict and ultimately prevent spontaneous abortion. Thus, there is an unmet need for a method of detecting and determining the risk of miscarriage in pregnant women.

Summary of The Invention

In one aspect, the invention relates to a method of identifying the risk of miscarriage comprising detecting and measuring the concentration of at least one metabolite in a sample obtained from a subject, wherein the absence or presence of a metabolite selected from the group consisting of tetrahydrocortisone, propionyl-carnitine, isovaleryl-carnitine, 3-methylglutaryl-carnitine, caproyl-carnitine and 3 α,20 α -dihydroxy-5 β -pregnan-3-glucuronide identifies an increased risk of miscarriage compared to a control group.

In another aspect, the invention relates to a method for identifying the risk of abortion, the method comprising measuring the concentration of at least one metabolite in a sample obtained from a subject, and comparing the concentration of the at least one metabolite with the concentration of the corresponding metabolite in a control group, wherein the metabolite is selected from the group consisting of tetrahydrocortisone, propionyl carnitine, isovaleryl carnitine, 3-methylglutaryl carnitine, hexanoyl carnitine and 3 α,20 α -dihydroxy-5 β -pregnan-3-glucuronide.

In another aspect, the present invention relates to a kit for identifying the risk of spontaneous abortion according to the method as described herein.