Compositions for ovary function modulation

Abstract

To provide compositions for modulating ovary functions.SOLUTION: The inventors have elucidated that bile acid substances have excellent effects on promotion of follicle growth, improvement of embryo incidence rate, enhancement of ovulation and reduction of ROS of ovum. One aspect provides compositions comprising bile acid substances for modulating ovary functions.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The technical field of the present invention relates to ovarian function regulating compositions. [Background technology]

[0002] The number of eggs ovulated in a lifetime is less than 0.1% of all germ cells. If the remaining 99.9% or more of the undeveloped follicles present in the ovaries could be effectively utilized, it could contribute to increasing livestock production and preserving endangered species in the agricultural field, and to infertility treatment in the medical field, and is therefore a technology that has long been desired. On the other hand, FXR is a nuclear receptor that is expressed mainly in the liver and intestine and functions to maintain the homeostasis of various nutrients, including cholesterol, lipids, and sugars. The world's first FXR knockout mice, generated in 2000, showed no abnormalities in reproductive function, leading to the conclusion that FXR is not a factor involved in reproduction (Non-Patent Document 1). However, we have reported that FXR is present in ovarian follicle cells and is involved in sex hormone synthesis (Non-Patent Document 2). Furthermore, we independently generated FXR knockout mice and found that follicular development and the number of ovulated oocytes were significantly increased. Furthermore, in an in vitro follicle culture system of wild-type mice, the addition of the FXR agonist GW4064 to the culture medium significantly suppressed follicular development, demonstrating the involvement of FXR in follicular development (Non-Patent Document 4). Bear bile, which has long been used in traditional Chinese medicine, is used as a medicine for the general digestive system, including stomachic and choleretic effects, but it has also been said to have various other benefits as a panacea. For example, ursodeoxycholic acid (UDCA), the main component of bear bile, is known as a partial agonist that partially inactivates FXR, and is already commonly used as a treatment for gallstones and liver disease, as well as for stomach upset and indigestion. [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] Signal CJ ​​et al., Cell. 2000 Sep 15;102(6):731-44 [Non-patent document 2] Takae K et al., J Reprod Dev. 2019 Feb 8;65(1):47-55 [Non-patent document 3] Koichi Watanabe et al., Elucidation of the mechanism of ovulation suppression by FXR, a key metabolic control factor, 26th Annual Meeting of the Japanese Society of Reproductive Endocrinology, 2022 [Non-patent document 4] Ikuo Tomioka et al., Promotion of follicle development by FXR regulation, 41st Japanese Society of Fertilization and Implantation, 2023 Summary of the Invention [Problem to be solved by the invention]

[0004] Although various findings have been accumulated to date, conventional techniques for utilizing immature follicles have not been sufficient. [Means for solving the problem]

[0005] After extensive research, the inventors discovered that FXR, previously thought to be unrelated to reproduction, can be effectively promoted by culturing ovarian and ovarian follicles in vitro with the addition of ursodeoxycholic acid, a bile acid that acts as an FXR ligand. Furthermore, in the utilization of undeveloped follicles in infertility treatment and livestock farming, a non-invasive approach is desirable to reduce the burden on the mother. Therefore, the inventors further conducted experiments in which bile acid substances were orally administered to living organisms. The results demonstrated that bile acid substances have excellent effects on improving the rate of fertilization, promoting ovulation, and reducing ROS in eggs, leading to the completion of this invention.

[0006] According to one aspect of the present invention, there is provided a composition for regulating ovarian function, which comprises a bile acid substance. Use of this composition can produce an excellent regulating effect of ovarian function.

[0007] The bile acid substance may be cholic acid, chenodeoxycholic acid, glycocholic acid, glucochenodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, α-muricholic acid, β-muricholic acid, ω-muricholic acid, deoxycholic acid, lithocholic acid, ursocholic acid, ursodeoxycholic acid, tauroursodeoxycholic acid, glycoursodeoxycholic acid, isocholic acid, isochhenodeoxycholic acid, isodeoxycholic acid, isolithocholic acid, 12-epideoxycholic acid, 12-oxochenodeoxycholic acid, 7-oxodeoxycholic acid, 7-oxolithocholic acid, 3-oxocholic acid, 3-oxochenodeoxycholic acid, phenylaranocholic acid, tyrosocholic acid, or leucholic acid. [Brief explanation of the drawings]

[0008] [Figure 1] FIG. 1 shows the experimental design of Example 1. [Figure 2] FIG. 2 is a line graph showing changes in the body weight of the mice measured during the 3-week feeding period. [Figure 3] FIG. 3 is a graph showing a representative estrous cycle for each group. [Figure 4] FIG. 4 is a graph showing the average number of superovulated eggs in each group. [Figure 5] FIG. 5 is a graph showing the average number of naturally ovulated eggs in each group. [Figure 6] FIG. 6 is a graph showing the rate of fertilized eggs in each group. [Figure 7] FIG. 7 shows images of superovulated oocytes in each group fluorescently stained for reactive oxygen species, and a graph showing the average fluorescence brightness. [Figure 8] FIG. 8 is a graph showing the numbers of primordial follicles, primary follicles, and secondary follicles in each group in the in vitro-cultured ovaries of Example 2. [Figure 9] Figure 9 shows images of fluorescently stained reactive oxygen species in in vitro matured oocytes. [Figure 10] FIG. 10 is a graph showing the average fluorescence intensity of the images in FIG. DETAILED DESCRIPTION OF THE INVENTION

[0009] Hereinafter, embodiments of the present invention will be described in detail, with the same contents omitted as appropriate to avoid repetition.

[0010] (1) Composition According to one embodiment of the present invention, there is provided a composition for regulating ovarian function, which contains a bile acid substance. Use of this composition can produce an excellent ovarian function regulating effect, as demonstrated in the examples described below.

[0011] The composition according to this embodiment can regulate ovarian function. The ovaries include follicles or oocytes, including isolated ovaries, follicles, or oocytes. Ovarian function may be assessed using indicators such as the rate of fertilization, the number of ovulations, the ROS level in oocytes, and / or the developmental stage of follicular growth.

[0012] The composition according to this embodiment may be used for increasing the rate of fertilized eggs, promoting ovulation, reducing reactive oxygen species (ROS) in eggs, and / or promoting follicle development.

[0013] In one embodiment of the present invention, fertilization may be performed in vivo or in vitro, and development of fertilized eggs may be performed in vivo or in vitro. Development of fertilized eggs refers to the progression of fertilized eggs through sequential developmental stages, such as the 2-cell stage, the 4-cell stage, the 8-cell stage, the morula, and the blastocyst, at a rate typically expected by those skilled in the art, without cleavage occurring differently from the typically expected cleavage pattern known to those skilled in the art. The rate of fertilized egg development refers to the percentage of fertilized eggs that have reached each typically expected developmental stage (e.g., the 2-cell stage, the 4-cell stage, the 8-cell stage, the morula, and the blastocyst) at a certain point after fertilization. An increase in the rate of fertilized egg development refers to an increase in the rate of fertilized egg development in individuals who have ingested the composition compared to that in individuals who have not ingested the composition, or an increase in the rate of fertilized egg development when fertilized eggs collected from individuals are cultured in a medium containing the composition compared to that when the eggs are cultured in a medium not containing the composition.

[0014] In one embodiment of the present invention, the increase in the rate of fertilized egg development in individuals who have ingested the composition may be 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, or 10% or more relative to the rate of fertilized egg development in individuals who have not ingested the composition.

[0015] In one embodiment of the present invention, ovulation may be natural ovulation or ovulation induced by superovulation treatment. Promotion of ovulation refers to an increase in the number of naturally ovulated eggs or superovulated eggs in an individual who has ingested the composition compared to an individual who has not ingested the composition.

[0016] In one embodiment of the present invention, the increase in the number of superovulated eggs in an individual who has ingested the composition may be 20, 25, 30, 35, 40, 45, or 50% or more relative to the number of superovulated eggs in an individual who has not ingested the composition.

[0017] In one embodiment of the present invention, the increase in the number of naturally ovulated eggs in an individual who ingests the composition may be 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, or 10% or more relative to the number of naturally ovulated eggs in an individual who does not ingest the composition.

[0018] In one embodiment of the present invention, reactive oxygen species (ROS) in oocytes refers to the ROS level in oocytes ovulated by natural ovulation or superovulation treatment, and a reduction in reactive oxygen species (ROS) in oocytes refers to a reduction in the ROS level in oocytes of individuals ingesting the composition compared to the ROS level in individuals not ingesting the composition. Alternatively, a reduction in reactive oxygen species (ROS) in oocytes refers to a reduction in the ROS level in oocytes cultured in a medium containing the composition compared to the ROS level in oocytes cultured in a medium not containing the composition. ROS levels may be assessed by fluorescent staining methods well known to those skilled in the art.

[0019] In one embodiment of the invention, the reduction in reactive oxygen species levels in an individual ingesting the composition may be 5, 10, 15, 20, or 25% or more relative to the reactive oxygen species levels in an individual not ingesting the composition.

[0020] In one embodiment of the present invention, follicular development may be performed in vivo or in vitro. Follicular development refers to the sequential progression of primordial follicles through developmental stages, such as primary, secondary, and tertiary (Grafian) follicles, at a rate typically expected by those skilled in the art, without undergoing morphological changes different from the typically expected developmental pattern known to those skilled in the art. Promotion of follicular development refers to an increase in the proportion of follicles that have reached each typically expected developmental stage (e.g., primary, secondary, and tertiary (Grafian) follicles) at a given point in time. Promotion of follicular development refers to the promotion of follicular development in an individual who has ingested the composition compared to follicular development in an individual who has not ingested the composition, or the promotion of follicular development in follicles collected from an individual and cultured in a medium containing the composition compared to follicular development in a medium not containing the composition.

[0021] In one embodiment of the present invention, the increase in the proportion of primary or secondary follicles in follicles cultured in a medium containing the composition may be 10, 15, 20, 25, 30, 35, 40, 45, 50, or 55% or more compared to when cultured in a medium not containing the composition.

[0022] The composition according to this embodiment may be used for treating or ameliorating infertility. Treatment or amelioration includes exerting an effect of alleviating symptoms, suppressing an effect of suppressing recurrence, or preventing an effect of treating a target disease or one or more symptoms associated with the disease.

[0023] According to one embodiment of the present invention, the bile acid substance may be cholic acid, chenodeoxycholic acid, glycocholic acid, glucochenodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, α-muricholic acid, β-muricholic acid, ω-muricholic acid, deoxycholic acid, lithocholic acid, ursocholic acid, ursodeoxycholic acid, tauroursodeoxycholic acid, glycoursodeoxycholic acid, isocholic acid, isochhenodeoxycholic acid, isodeoxycholic acid, isolithocholic acid, 12-epideoxycholic acid, 12-oxochenodeoxycholic acid, 7-oxodeoxycholic acid, 7-oxolithocholic acid, 3-oxocholic acid, 3-oxochenodeoxycholic acid, phenylaranocholic acid, tyrosocholic acid, or leucholic acid.

[0024] In one embodiment of the present invention, the composition may be in the form of, for example, a pharmaceutical product, a food or drink, or an ovarian culture medium or additive. Pharmaceutical products include, for example, pharmaceutical compositions for infertility treatment. In addition to the bile acid substance according to the above embodiment, the composition may further contain any component suitable for regulating ovarian function. The content of the bile acid substance according to the above embodiment in the composition is not particularly limited and can be selected appropriately depending on the purpose.

[0025] The components other than the bile acid substance in the composition are not particularly limited as long as they do not impair the effects of the present invention, and can be appropriately selected from components used in pharmaceuticals, foods and beverages, culture media, etc., such as known bile acid substances, depending on the dosage form. Examples include nonionic surfactants, sugars, sugar alcohols, polysaccharides, polyacrylic acid, polyethylene oxide, polyethylene glycol, polyvinylpyrrolidone, hydroxyethyl cellulose, hydroxypropyl cellulose, starch, etc. These may be used alone or in combination of two or more. The content of these components in the composition is not particularly limited and can be appropriately selected depending on the purpose.

[0026] The amount of the composition to be administered to an individual is not particularly limited and can be appropriately selected taking into consideration the age, weight, and presence or absence of diseases of the individual to be treated, and examples of the amount administered at one time include 0.05 mg / kg to 2 g / kg.

[0027] The composition may be used alone or in combination with a medicine containing another ingredient as an active ingredient. The composition may also be used in a state where it is incorporated into a medicine containing another ingredient as an active ingredient.

[0028] The mode of use of the above-mentioned composition is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include oral, transdermal, enteral, transmucosal, intravenous, intraarterial, subcutaneous, intramuscular, intraperitoneal, etc. These may be used alone or in combination of two or more.

[0029] The dosage form of the above-mentioned composition is not particularly limited, and a known dosage form can be appropriately selected depending on the mode of use, etc. The dosage form may be solid, semi-solid, or liquid, and examples thereof include oral administration preparations such as tablets, granules, powders, capsules, soft capsules, and syrups; transdermal or transmucosal administration preparations such as liquids, ointments, creams, gels, sprays, patches, inhalants, and suppositories; and injections. These dosage forms of ovarian function regulators can be produced by known methods.

[0030] There are no particular limitations on the administration interval of the above composition, and it can be appropriately selected taking into consideration the age, weight, and presence or absence of diseases of the subject individual.

[0031] The individual to which the composition is administered is not particularly limited and can be appropriately selected depending on the purpose. The subject may be a vertebrate, such as a mammal, a bird, a reptile, an amphibian, or a fish. Examples include humans, mice, rats, cattle, pigs, sheep, goats, horses, monkeys, dogs, cats, chickens, Japanese crested ibises, turtles, and eels. The subject may also be a patient. The subject may be a patient diagnosed with infertility or a patient in need of treatment. The subject may be an economic animal or a pet, or an endangered animal.

[0032] When using the above composition in an ovary in vitro culture system, the mode of use, dosage form, amount added to the culture system, addition interval, subjects from which the ovaries are removed, and subjects to be subjected to natural ovulation or superovulation treatment are not particularly limited and can be selected appropriately depending on the purpose.

[0033] (2) Pharmaceutical composition According to one embodiment of the present invention, there is provided a pharmaceutical composition comprising a bile acid substance, optionally including a pharmaceutically acceptable carrier, which can be used to treat a disease.

[0034] According to one embodiment of the present invention, there is provided a pharmaceutical composition containing a bile acid substance for treating infertility. This pharmaceutical composition can be used to treat infertility.

[0035] In one embodiment of the present invention, the pharmaceutical composition may be prepared by, for example, mixing an active ingredient with one or more pharmacologically acceptable carriers and using any method known in the technical field of pharmaceuticals. Furthermore, the pharmaceutical composition may be used in any form, as long as it is used for treatment. It may contain the active ingredient alone or a mixture of the active ingredient with any other ingredient. The form of the carrier is also not particularly limited, and may be, for example, a solid or liquid (e.g., a buffer solution). The content of the carrier may be, for example, a pharmaceutically effective amount. This effective amount may be, for example, an amount sufficient for pharmaceutical stability or delivery of the active ingredient. For example, a buffer solution is effective for stabilizing the active ingredient in a vial. Preferably, the pharmaceutical composition contains a therapeutically effective amount of the active ingredient, or an amount effective to exert the desired effect.

[0036] In one embodiment of the present invention, the disease to be treated can be appropriately selected depending on the purpose, and includes, for example, infertility. Infertility includes, for example, ovulation disorders and underdevelopment of follicles and fertilized eggs, including those caused by hyperprolactinemia and polycystic ovary syndrome.

[0037] (3) Treatment method According to one embodiment of the present invention, there is provided a method of treatment using a bile acid substance, which may include administering to a subject a composition comprising a bile acid substance. Such a method can be used to treat a subject.

[0038] (4) Therapeutic use According to one embodiment of the present invention, there is provided a use of bile acid substances for the treatment of diseases, whereby a subject can be treated.

[0039] (5) Use in the manufacture of pharmaceuticals According to one embodiment of the present invention, there is provided a use of a bile acid substance in the manufacture of a medicament for regulating ovarian function or treating infertility, which can be used to manufacture a medicament for regulating ovarian function or treating infertility in a subject.

[0040] (5)Food and beverages According to one embodiment of the present invention, a food or drink containing a bile acid substance is provided. The use of such a food or drink can produce an excellent ovarian function regulating effect. In one embodiment of the present invention, the food or drink may be a food or beverage product. Food or drink includes those that can be taken orally, and includes, for example, general food and drink, as well as foods for specified health uses, nutritional supplements, functional foods, and foods for the sick. Food and drink may be in the form of, for example, a supplement. Food and drink may contain additives such as flavorings, colorings, or preservatives. Known methods can be used as appropriate to produce the food or drink depending on the type of food or drink.

[0041] (6) How to eat and drink According to one embodiment of the present invention, there is provided a method for consuming a bile acid substance. This method may include a step of having a subject ingest a composition containing the bile acid substance. Such a method can produce an excellent ovarian function regulating effect.

[0042] (7) Ovarian culture medium or additives According to one embodiment of the present invention, there is provided a medium or additive for ovarian culture containing a bile acid substance, which can exert an excellent ovarian function regulating effect, such as reducing reactive oxygen species (ROS) in oocytes and / or promoting follicle development.

[0043] (8)Cell culture method According to one embodiment of the present invention, there is provided a method for culturing ovaries using a bile acid substance. This method may include adding a composition containing a bile acid substance to a culture medium. Such an ovary culture method can produce excellent ovarian function regulating effects, such as reducing reactive oxygen species (ROS) in oocytes and / or promoting follicle development.

[0044] (9) Production method According to one embodiment of the present invention, there is provided a method for producing a composition containing a bile acid substance. The composition containing albumin obtained by such a production method can be used to exert an excellent ovarian function regulating effect.

[0045] According to one embodiment of the present invention, there is provided a use of bile acid substances for producing a pharmaceutical composition for treating diseases, and the pharmaceutical composition obtained by such a production use can produce an excellent ovarian function regulating effect.

[0046] All publications cited herein are incorporated by reference in their entirety. In this specification, "or" is used when "at least one or more" of the items listed in the text can be employed. The same applies to "alternative." In this specification, when it is stated that "within a range of two values," the range also includes the two values ​​themselves. In this specification, "A to B" includes A and B.

[0047] Although the embodiments of the present invention have been described above, these are merely examples of forms that may be included in the present invention, and the present invention is not limited to these, and various configurations other than those described above may also be adopted. Furthermore, the present invention may be adopted by combining or independently adopting each of the configurations or features described in the above embodiments. [Example]

[0048] The present invention will be further explained below with reference to examples, but is not limited to these.

[0049] Example 1 Experimental design The experimental design is shown in Figure 1. Female mice were divided into three groups: a control group fed a normal diet (NMF; Oriental Yeast Co., Ltd.); a CDCA-fed group fed a diet supplemented with 0.4% chenodeoxycholic acid (CDCA; Fujifilm Wako Pure Chemical Industries, Ltd.), an FXR activator; and a UDCA-fed group fed a diet supplemented with 0.4% ursodeoxycholic acid (UDCA; Fujifilm Wako Pure Chemical Industries, Ltd.), an FXR inactivator. The "0.4%" level was calculated based on the human intake and was sufficient for mice. Feeding began at 3 weeks of age, the time required for ovarian follicles to develop into the follicles immediately prior to ovulation. The following experiments were performed during and after the feeding period to investigate the effects of CDCA and UDCA feeding on follicular development and ovulation.

[0050] 1.Weight measurement The body weight of each group was measured once a week from the start of feeding.

[0051] The results are shown in Figure 2. There were no differences between the groups in any of the weeks, and all groups steadily gained weight.

[0052] 2. Observation of estrous cycle and mating behavior One week after the start of feeding, vaginal smears were collected every morning at 9:00 a.m. to examine the estrous cycle, which was divided into four phases: proestrus, estrus, metaestrus, and telogen.

[0053] Representative results for each group are shown in Figure 3. In each group, there were a certain number of mice with estrous cycles (left column in Figure 3) and mice without estrous cycles (right column in Figure 3). During the 12-day test period, the control group and CDCA-fed group had an average of 1.5 estrous cycles, and the UDCA-fed group had an average of 1.6 cycles, with no significant difference between the groups.

[0054] As with the control group, mice in the CDCA- and UDCA-fed groups mated normally.

[0055] 3. Counting the number of superovulated oocytes, staining for reactive oxygen species, and measuring brightness After three weeks of feeding, mice from each group were hormonally treated to induce superovulation, and the number of superovulated oocytes was counted and compared. Hormone treatment was performed by intraperitoneally injecting 10 IU of PMSG (Asuka Animal Health Co., Ltd.), followed 48 hours later by intraperitoneally injecting 10 IU of hCG (Asuka Animal Health Co., Ltd.). Oocytes were collected 15 hours or later after hCG treatment. The resulting superovulated oocytes were stained using a ROS assay kit (DOJINDO) according to the protocol provided, and then observed under a Keyence fluorescence microscope and analyzed for fluorescence intensity using ImageJ.

[0056] The results of counting the number of superovulated oocytes are shown in Figure 4. Compared with the control group, the average number of superovulated oocytes was significantly higher in the CDCA-fed group and tended to be higher in the UDCA-fed group.

[0057] The results of staining and measurement of reactive oxygen species (ROS) are shown in Figure 7. Compared to the control group, the amount of reactive oxygen species in the oocytes was significantly reduced in the CDCA-fed and UDCA-fed groups. This result indicates that the quality of the oocyte cytoplasm is improved in the CDCA-fed and UDCA-fed groups, which is thought to be the reason for the increased rate of fertilized eggs in the experiment shown in Figure 6.

[0058] 4. Counting the number of naturally ovulated eggs and measuring the rate of fertilized eggs After three weeks of feeding, the mice were mated with male mice, and eggs were collected after mating to compare the number of naturally ovulated eggs.Furthermore, the collected fertilized eggs were cultured to determine the fertilized egg development rate.

[0059] The results of counting the number of naturally ovulated oocytes are shown in Figure 5. Although there was no significant difference in the number of naturally ovulated oocytes between the groups, there was a tendency for the CDCA-fed group and the UDCA-fed group to have a higher number.

[0060] The results of measuring the rate of fertilized egg development are shown in Figure 6. The CDCA-fed and UDCA-fed groups tended to have a higher rate of fertilized egg development, and the UDCA-fed group in particular had a significantly higher rate of fertilized egg development than the control (CTL) group.

[0061] Example 2 Ovaries were harvested from 8-day-old wild-type mice, and the left ovaries were cultured as a control (CTL) group and the right ovaries as a ursodeoxycholic acid (UDCA)-treated group for 4 days. The ovaries were then fixed, embedded in paraffin, serially sectioned, and the follicles were counted. The results are shown in Figure 8. Compared to the control (CTL) group, the UDCA-added group showed a decrease in the number of primordial follicles, a significant increase in the number of activated primary follicles, and a tendency toward a significant increase in the number of developed secondary follicles. These results demonstrate that UDCA can activate primordial follicles and promote follicular development.

[0062] Example 3 Staining and brightness measurement of reactive oxygen species in in vitro matured oocytes Mice were treated with hormones to induce follicular development, and immature oocytes were collected. Hormone treatment was performed by intraperitoneal injection of 10 IU PMSG (Asuka Animal Health Co., Ltd.). Oocytes were collected 48 hours after PMSG treatment. The obtained immature oocytes were then cultured for 24 hours in a medium containing no or 100 μM UDCA to obtain mature oocytes. The obtained mature oocytes were stained using a ROS assay kit (DOJINDO) according to the protocol provided, and observed under a Keyence fluorescence microscope and analyzed for fluorescence intensity using ImageJ. The results of staining and measurement of reactive oxygen species (ROS) are shown in Figures 9 and 10. Compared to the control (CTL) group, the amount of reactive oxygen species in the eggs in the UDCA-added group was significantly reduced. This result indicates that the quality of the egg cytoplasm is improved by the addition of UDCA, which is thought to be the reason for the increased rate of fertilized eggs in the experiment shown in Figure 6. In the UDCA feeding experiment on individual mice, it was not clear how the ingested UDCA affected the egg cells, but the data from this experiment showed that UDCA acts directly on egg cells and has the effect of reducing ROS.

[0063] The present invention has been described above based on the embodiments. However, these embodiments are merely illustrative, and it will be understood by those skilled in the art that various modifications are possible and that such modifications are also within the scope of the present invention.

Claims

1. A composition for regulating ovarian function, comprising a bile acid substance.

2. The composition for regulating ovarian function according to claim 1, which is used to increase the rate of fertilized eggs, promote ovulation, reduce reactive oxygen species (ROS) in eggs, and / or promote follicle development.

3. The composition for regulating ovarian function according to claim 1, which is used for treating or improving infertility.

4. The composition according to any one of claims 1 to 3, wherein the bile acid substance is cholic acid, chenodeoxycholic acid, glycocholic acid, glucochenodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, α-muricholic acid, β-muricholic acid, ω-muricholic acid, deoxycholic acid, lithocholic acid, ursocholic acid, ursodeoxycholic acid, tauroursodeoxycholic acid, glycoursodeoxycholic acid, isocholic acid, isochhenodeoxycholic acid, isodeoxycholic acid, isolithocholic acid, 12-epideoxycholic acid, 12-oxochenodeoxycholic acid, 7-oxodeoxycholic acid, 7-oxolithocholic acid, 3-oxocholic acid, 3-oxochenodeoxycholic acid, phenylaranocholic acid, tyrosocholic acid, or leucholic acid.

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