Application of pyrroloquinoline quinone in preparation of product for improving polycystic ovarian syndrome

Abstract

The invention provides application of pyrroloquinoline quinine or pyrroloquinoline quinine salt in preparation of a product for treating and / or improving the ovulation function of polycystic ovarian syndrome and improving fertility. Through the product, the ovarian polycystic form of a PCOS patient can be improved, sex hormone secretion disorder can be improved, the estrus cycle can be adjusted, ovarian fibrosis can be improved, oocyte maturation can be promoted, early embryonic development potential can be improved, and pregnancy can be promoted.

Description

Technical Field

[0001] The present invention relates to the field of medicine, and in particular to the use of pyrroloquinoline quinone in treating and / or improving the ovulation function of polycystic ovary syndrome and enhancing fertility. Background Art

[0002] Polycystic ovary syndrome (PCOS) is a complex syndrome of endocrine and metabolic disorders and is the primary cause of anovulatory infertility in women. Clinically, it is characterized by anovulation, polycystic ovaries, and elevated androgen levels, with major clinical manifestations including irregular menstruation, infertility, obesity, and insulin resistance. While assisted reproductive technology offers the opportunity for women with PCOS to have children, ovulation induction therapy is associated with significant side effects. Furthermore, women with PCOS often experience oocyte immaturity and low embryonic potential during in vitro fertilization and embryo transfer, resulting in suboptimal assisted reproductive outcomes.

[0003] Numerous drugs for ovarian protection have been disclosed in the prior art, but most of them are ineffective for anovulatory infertility in PCOS patients. Therefore, finding drugs that can effectively improve ovulation function and enhance fertility in PCOS patients is of great clinical significance. Summary of the Invention

[0004] In view of this, the technical problem to be solved by the present invention is to provide a drug for improving the ovulation function and fertility of patients with polycystic ovary syndrome. The pyrroloquinoline quinone provided by the present invention can treat and / or improve the ovulation function and improve the fertility of patients with polycystic ovary syndrome.

[0005] Pyrroloquinoline quinone (PQQ), a cofactor of cytochrome C oxidase, is a powerful natural antioxidant found widely in soil, plant and animal tissues, and breast milk. PQQ can capture and scavenge free radicals through the pyrrole ring and ketone groups in its molecular structure, while also activating multiple endogenous antioxidant enzyme systems to protect cells from oxidative stress. Humans cannot synthesize PQQ themselves, but they can obtain it from food. A lack of PQQ in the mammalian diet can lead to reproductive dysfunction, abnormal growth and development, and immune system-related complications. Studies have shown that PQQ can protect mouse ovaries from ischemia-reperfusion injury and alleviate follicle loss caused by chemotherapy drugs. Furthermore, PQQ can regulate insulin signaling, modulate glucose transporter translocation, increase glucose absorption, and improve energy metabolism.

[0006] The present invention provides the use of pyrroloquinoline quinone or a pyrroloquinoline quinone salt in preparing a product for treating and / or improving the ovulation function of polycystic ovary syndrome and enhancing fertility.

[0007] The inventors screened numerous drugs and creatively discovered that the pyrroloquinoline quinone or pyrroloquinoline quinone salt has the following effects, while being more stable and safer than other drugs. Compared with other drugs, it has significant advantages in the following effects.

[0008] According to the present invention, the treatment and / or improvement of polycystic ovary syndrome ovulation function and fertility enhancement include one or more of the following:

[0009] 1) Improve the polycystic ovarian morphology of PCOS patients;

[0010] II) Improve the imbalance of sex hormone secretion in PCOS patients;

[0011] III) Adjust the estrus cycle of PCOS patients;

[0012] IV) Improve sugar metabolism in PCOS patients

[0013] V) Improve ovarian fibrosis in PCOS patients;

[0014] VI), promoting oocyte maturation in PCOS patients;

[0015] VII) Enhance the early embryonic development potential and promote pregnancy in PCOS patients.

[0016] The present invention's treatment and / or improvement of polycystic ovary syndrome ovulation function and fertility enhancement includes improving the polycystic morphology of the ovaries of PCOS patients;

[0017] The experimental results of the present invention show that PQQ treatment can restore the ovaries of PCOS mice to normal morphology and the follicles are in different developmental stages.

[0018] The present invention's treatment and / or improvement of ovulation function and fertility enhancement in polycystic ovary syndrome includes improving the imbalance of sex hormone secretion in PCOS patients;

[0019] The experimental results of the present invention show that PQQ treatment can significantly reduce the testosterone level in the serum of PCOS mice.

[0020] The present invention provides for treating and / or improving the ovulation function and enhancing fertility of polycystic ovary syndrome, including adjusting the estrus cycle of PCOS patients.

[0021] The experimental results of the present invention show that PQQ treatment can improve the estrous cycle disorder of PCOS mice and make the estrous cycle regular.

[0022] The present invention's method of treating and / or improving ovulation function and enhancing fertility of polycystic ovary syndrome includes improving glucose metabolism in PCOS patients.

[0023] According to the present invention, improving sugar metabolism includes improving glucose tolerance, insulin tolerance and / or reducing body weight in PCOS patients.

[0024] The present inventors evaluated the glucose metabolism of mice through glucose tolerance test, insulin tolerance test and body weight monitoring, and found that PQQ can improve the glucose tolerance of PCOS mice, significantly improve the insulin tolerance of PCOS mice and significantly reduce the body weight of PCOS mice.

[0025] The present invention provides for treating and / or improving ovulatory function and enhancing fertility in polycystic ovary syndrome (PCOS) by improving ovarian fibrosis. Specifically, improving ovarian fibrosis in PCOS patients includes reducing the percentage of ovarian tissue sirius red-stained positive area and reducing the expression levels of ovarian fibrosis-related molecules. These ovarian fibrosis-related molecules include CTGF, TGFβ, and / or PPARγ.

[0026] The present inventors detected the ovarian fibrosis level of mice by picrosirius red staining experiment and the expression levels of ovarian fibrosis-related molecules CTGF, TGFβ, and PPARγ in mouse ovarian tissue by RT-qPCR experiment, and found that PQQ can improve ovarian fibrosis in PCOS mice.

[0027] The present invention provides a method for treating and / or improving ovulation function and enhancing fertility in PCOS patients, including promoting oocyte maturation. In the present invention, promoting oocyte maturation in PCOS patients includes reducing the rate of meiotic spindle abnormalities in MII oocytes and / or promoting the release of the first polar body in GV-stage oocytes cultured in vitro.

[0028] The inventors performed spindle immunofluorescence staining on mouse MII oocytes and observed the spindle morphology using confocal microscopy, finding that PQQ significantly reduced the rate of spindle abnormalities in MII oocytes from PCOS mice. The inventors also cultured GV-stage oocytes in vitro and found that PQQ significantly increased the rate of first polar body extrusion in GV-stage oocytes from PCOS mice.

[0029] The present invention provides for treating and / or improving ovulation function and enhancing fertility in PCOS patients, including enhancing early embryonic development potential and / or promoting pregnancy. Improving early embryonic development potential includes increasing the 4-cell formation rate and / or blastocyst formation rate in PCOS mice. Promoting pregnancy in the present invention involves shortening the time to first litter birth in PCOS mice.

[0030] The products of the present invention include medicines, health products or functional foods; the products are oral preparations; the dosage forms of the products include tablets, capsules, oral liquids, lozenges, granules, fat emulsions, microcapsules, pellets, granules, powders, ointments, pills, suspensions, powders and solutions.

[0031] The above-mentioned product provided by the present invention also includes conventional auxiliary materials used by those skilled in the art, which are not limited by the present invention and are well known to those skilled in the art.

[0032] In some embodiments provided herein, the pharmaceutically acceptable excipient is one or a mixture of two or more of fruit powder, flavoring, sweetener, acidulant, filler, lubricant, preservative, suspending agent, food coloring, diluent, emulsifier, disintegrant, or plasticizer. The present invention is not limited thereto and any of the foregoing is known to those skilled in the art.

[0033] The present invention also provides a method for treating and / or improving ovulation function and enhancing fertility in polycystic ovary syndrome, comprising administering the above-mentioned drug.

[0034] The routes of administration include oral administration, injection (including intravenous injection, intramuscular injection, subcutaneous injection, intradermal injection, etc.), inhalation, sublingual administration, rectal administration, vaginal administration, topical application (including skin, mucous membranes, etc.), and transdermal administration.

[0035] The subject of treatment and / or improvement can be a human or a mammal, and the mammal includes mice, rats, guinea pigs, rabbits, dogs, monkeys, and pigs.

[0036] The present invention provides the use of pyrroloquinoline quinone or a pyrroloquinoline quinone salt in the preparation of a product for treating and / or improving ovulation and fertility in patients with polycystic ovary syndrome (PCOS). Supplementation with pyrroloquinoline quinone has been shown to improve the polycystic ovarian morphology, improve sex hormone imbalance, regulate estrous cycles, improve glucose metabolism, improve ovarian fibrosis, promote oocyte maturation, enhance early embryonic developmental potential, and shorten the time to first birth in PCOS patients. In a dehydroepiandrosterone-induced PCOS mouse model, oral administration of pyrroloquinoline quinone improved the polycystic ovarian morphology of PCOS mice, regularized their estrous cycles, alleviated sex hormone imbalances, improved glucose and insulin tolerance, and significantly reduced their body weight. It also significantly reduced ovarian fibrosis and the expression of fibrosis-related factors, significantly reduced the rate of meiotic spindle abnormalities in oocytes, significantly increased the maturation rate of GV-stage oocytes in vitro, and significantly increased the four-cell formation rate and blastocyst formation rate of oocytes subjected to in vitro fertilization, shortening the time to first litter. In vivo mouse studies suggest that pyrroloquinoline quinone can improve ovulation, promote oocyte maturation, enhance early embryonic developmental potential, and promote pregnancy in PCOS patients. It has promising potential for the development of drugs, health supplements, or functional foods to treat and / or improve ovulation and enhance fertility in PCOS. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 These are the experimental results of Example 1 showing that supplementation of PQQ improves the polycystic ovarian morphology, enhances the regularity of the estrous cycle, and improves the imbalance of sex hormone secretion in PCOS mice. * indicates P < 0.05, and ** indicates P < 0.01.

[0038] Figure 2 The results of the experiment in Example 1 on improving glucose metabolism in PCOS mice by supplementing with PQQ. ** indicates P < 0.01.

[0039] Figure 3 The results of the experiment in Example 2 in which PQQ supplementation improved ovarian fibrosis in PCOS mice were shown in Table 2. ** indicates P < 0.01.

[0040] Figure 4 This is the experimental result of Example 3 in which PQQ supplementation reduced the abnormal morphology rate of meiotic spindle in MII oocytes of PCOS mice. * indicates P < 0.05.

[0041] Figure 5 The results of the experiment in Example 4 showing that supplementation of PQQ promoted in vitro maturation of GV-stage oocytes in PCOS mice. * indicates P < 0.05.

[0042] Figure 6The results of the experiment in Example 5 show that supplementation of PQQ improves the early embryonic development potential of MII oocytes in vitro fertilization of PCOS mice. ** indicates P < 0.01, and *** indicates P < 0.001.

[0043] Figure 7 The experimental results of Example 6 show that PQQ supplementation shortens the time to first litter birth in PCOS mice. * indicates P < 0.05.

[0044] Figure 8 Flowchart for the construction and PQQ treatment of PCOS model mice. DETAILED DESCRIPTION

[0045] The present invention provides the use of pyrroloquinoline quinone in treating and / or improving the ovulation function of polycystic ovary syndrome and improving fertility. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters to achieve the desired effect. It should be noted in particular that all similar replacements and modifications are obvious to those skilled in the art and they all fall within the scope of protection of the present invention. The methods and applications of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the methods and applications herein without departing from the content, spirit and scope of the present invention to implement and apply the technology of the present invention.

[0046] It should be understood that the expression "one or more of" includes individually each of the items recited after the expression and various combinations of two or more of the recited items, unless otherwise apparent from the context and usage. The expression "and / or" in conjunction with three or more recited items should be understood to have the same meaning, unless otherwise apparent from the context.

[0047] The terms "comprising", "having" or "containing", including their grammatical synonyms, should generally be understood as open and non-restrictive, e.g., not excluding other unrecited elements or steps, unless otherwise specifically stated or understood from the context.

[0048] In this application, the term "and / or" describes the association relationship between associated objects, indicating that three relationships may exist. For example, A and / or B can mean: A exists alone, A and B exist at the same time, and B exists alone. A and B can be singular or plural.

[0049] In this application, "at least one" means one or more, and "more than one" means two or more. "At least one of the following" or similar expressions refers to any combination of these items, including any combination of single or plural items.

[0050] In one embodiment of the present invention, a dehydroepiandrosterone (DHEA)-induced PCOS mouse model was constructed, and PQQ was administered orally for treatment. The ovarian morphology, estrous cycle, and sex hormone levels of the mice were detected by HE staining of ovarian tissue, vaginal smears, and serum sex hormone detection experiments. It was found that PQQ treatment can restore the normal morphology of the ovaries of PCOS mice, place the follicles in different developmental stages, improve the estrous cycle disorder of PCOS mice, and significantly reduce the serum testosterone (T) level and luteinizing hormone (LH) level of PCOS mice.

[0051] The glucose metabolism of mice was evaluated through glucose tolerance test, insulin tolerance test and body weight monitoring. It was found that PQQ can improve the glucose tolerance of PCOS mice, significantly improve the insulin tolerance of PCOS mice and significantly reduce the body weight of PCOS mice.

[0052] The fibrosis level of mouse ovarian tissue was detected by picrosirius red staining experiment, and the expression levels of ovarian fibrosis-related molecules CTGF, TGFβ, and PPARγ in mouse ovarian tissue were detected by RT-qPCR experiment. It was found that PQQ can improve ovarian fibrosis in PCOS mice.

[0053] Mouse MII oocytes were taken for spindle immunofluorescence staining, and the oocyte spindle morphology was observed using a confocal microscope. It was found that PQQ could significantly reduce the rate of meiotic spindle abnormalities in MII oocytes of PCOS mice.

[0054] Mouse GV stage oocytes were cultured in vitro, and it was found that PQQ can significantly improve the maturation rate of GV stage oocytes in PCOS mice.

[0055] Mouse MII oocytes were taken for in vitro fertilization and cultured to the blastocyst stage. It was found that the 4-cell formation rate and blastocyst formation rate of PCOS mice were significantly increased after PQQ treatment.

[0056] Each group of mice was caged with fertile male mice of reproductive age until the birth of the first litter of offspring. The time required for each group of mice from caged together to birth was counted, and it was found that PQQ treatment could shorten the time to first litter birth in PCOS mice.

[0057] In the above examples, it is proposed that PQQ supplementation can improve PCOS ovulation function, promote PCOS oocyte maturation, enhance early embryo development potential and promote pregnancy.

[0058] It should be understood that the order of steps or the order in which certain actions are performed are not important as long as the present invention remains operable. Additionally, two or more steps or actions may be performed simultaneously.

[0059] The use of any and all examples or exemplary language, such as "such as" or "including," herein is intended merely to better illustrate the invention and does not limit the scope of the invention unless otherwise claimed. No language in this specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

[0060] In addition, the numerical ranges and parameters used to define the present invention are approximate values. The relevant numerical values ​​in the specific examples have been presented as accurately as possible. However, any numerical value inherently inevitably contains standard deviations due to individual testing methods. Therefore, unless otherwise expressly stated, all ranges, amounts, values, and percentages used in this disclosure should be understood to be modified by the word "about." As used herein, "about" generally means that the actual value is within plus or minus 10%, 5%, 1%, or 0.5% of a specified value or range.

[0061] It should be understood that in the various embodiments of the present application, the size of the serial numbers of the above-mentioned processes does not mean the order of execution. Some or all of the steps can be executed in parallel or sequentially. The execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0062] Some cases are described in the embodiments and comparative examples of the present invention, wherein the embodiments illustrate certain implementations of the present invention. However, this does not mean that the effects of the present invention can only be achieved in these cases.

[0063] To further illustrate the present invention, the application of pyrroloquinoline quinone provided by the present invention in treating and / or improving ovulation function of polycystic ovary syndrome and enhancing fertility is described in detail below with reference to the examples.

[0064] Example 1 PQQ supplementation can improve the polycystic ovarian morphology of PCOS mice, enhance the regularity of estrous cycle, improve sex hormone secretion disorders, and improve glucose metabolism.

[0065] The experimental method is as follows: 21-day-old C57 female mice were subcutaneously injected with DHEA (60 mg / kg body weight) for 21 consecutive days to establish a PCOS mouse model. After the DHEA modeling was completed, vaginal smears were performed for 14 consecutive days to observe the estrous cycle of the mice. From the day of subcutaneous DHEA injection to the end of vaginal smears, the mice were gavaged with PQQ aqueous solution at a dose of 1 mg / kg body weight. The mice were weighed daily during this period. The estrous cycle, serum sex hormones, ovarian tissue HE staining, glucose tolerance and insulin tolerance tests were performed to evaluate the PCOS-like phenotype. The experimental results are as follows: Figure 1 and Figure 2 shown.

[0066] Figure 1Figure A shows that the ovaries of mice treated with DHEA exhibited an increase in the number of cystic and antral follicles, while the ovaries of mice treated with PQQ displayed normal morphology, with follicles at various stages of development. Figure B shows that the estrous cycles of mice treated with DHEA were irregular, with periods of prolonged stagnation. The estrous cycles of mice treated with PQQ became more regular compared to those in the DHEA group. Figure C shows that serum testosterone and luteinizing hormone levels were significantly higher in mice treated with DHEA than in the control group, while PQQ treatment significantly reduced these elevated levels. Figure 2 Figure A shows that glucose tolerance improved in the PQQ-treated group compared to the DHEA-treated group. Figure B shows that insulin tolerance was significantly lower in the DHEA-treated group than in the control group, while significantly higher in the PQQ-treated group. Figure C shows that the body weight of mice in the DHEA-treated group was significantly higher than in the control group, while the body weight of mice in the PQQ-treated group was significantly lower, suggesting that PQQ supplementation can improve glucose metabolism in PCOS mice.

[0067] Example 2 PQQ supplementation improves ovarian fibrosis in PCOS mice

[0068] The experimental method is as follows: Mouse ovarian tissue sections were stained with Sirius red (PSR) to detect the level of ovarian tissue fibrosis, and RNA was extracted from mouse ovarian tissue for RT-qPCR experiments to detect the expression levels of ovarian fibrosis-related molecules. The experimental results are as follows Figure 3 shown.

[0069] Figure 3 Figures A and B show that the area of ​​ovarian fibrosis in the DHEA group was significantly higher than in the control group, while the area of ​​ovarian fibrosis in the PQQ-treated group was significantly reduced. Figure C shows that the expression levels of ovarian fibrosis-related molecules CTGF and TGFβ-1 were significantly lower in the PQQ-treated group than in the DHEA group, while the expression level of PPARγ was significantly higher. This suggests that PQQ supplementation can improve ovarian fibrosis in PCOS mice.

[0070] Example 3 PQQ supplementation can reduce the rate of spindle abnormalities in oocytes of PCOS mice

[0071] Mice were superovulated by intraperitoneal injection of 7.5 IU pregnant mare serum gonadotropin (PMSG), and 48 hours later, 7.5 IU human chorionic gonadotropin (hCG) was injected. Mice were sacrificed 14 hours after hCG injection, and the oviducts were dissected and the cumulus-oocyte complexes were collected from the ampulla. Hyaluronidase was used to remove the cumulus cells and obtain MII oocytes. Immunofluorescence staining of the oocyte spindle was performed, and confocal microscopy was used to examine the spindle morphology. The experimental results are shown in Figure 2. Figure 4 shown.

[0072] Figure 4The results showed that the rate of abnormal spindle morphology of oocytes in the DHEA group was significantly higher than that in the control group, while PQQ treatment could significantly reduce the rate of abnormal spindle morphology of oocytes.

[0073] Example 4 PQQ supplementation can improve the in vitro maturation rate of GV-stage oocytes in PCOS mice

[0074] The experimental method is as follows: mice were superovulated by intraperitoneal injection of 7.5 IU pregnant mare serum gonadotropin (PMSG). Mice were sacrificed 48 hours later. Ovarian tissue was minced with a surgical blade to collect GV oocytes. They were cultured in vitro for 14 hours for in vitro maturation and the first polar body was observed. The experimental results are as follows: Figure 5 shown.

[0075] Figure 5 The results showed that the maturation rate of oocytes in the GV stage in the DHEA group was significantly lower than that in the control group, while the maturation rate of oocytes in the PQQ-treated group was significantly higher than that in the DHEA group, suggesting that PQQ supplementation can promote oocyte maturation in PCOS mice.

[0076] Example 5 PQQ supplementation can enhance the early embryonic development potential of PCOS mouse oocytes

[0077] The experimental method is as follows: Mice were superovulated by intraperitoneal injection of 7.5 IU of pregnant mare serum gonadotropin (PMSG), followed 48 hours later by an injection of 7.5 IU of human chorionic gonadotropin (hCG). Mice were sacrificed 14 hours after hCG injection, and the oviducts were dissected and the cumulus-oocyte complexes were collected from the ampulla and placed in a fertilization dish. Three- to four-month-old C57 male mice were sacrificed, and the epididymis was harvested. Sperm was released from the epididymis in human tubal fluid (HTF) medium. One hour after capacitation, a final concentration of 1 × 10 5 / ml of sperm was added to the fertilization medium. After 6 hours of fertilization, the eggs were transferred to KSOM medium for further culture. The cleavage rate was observed 24 hours after fertilization, the 4-cell rate was observed 48 hours after fertilization, and the blastocyst formation rate was observed 96 hours after fertilization. Figure 6 shown.

[0078] Figure 6 Figures A and B show that the 4-cell formation rate and blastocyst formation rate of oocytes from mice in the DHEA group after in vitro fertilization were significantly lower than those in the control group, while the 4-cell formation rate and blastocyst formation rate of oocytes from mice in the PQQ treatment group were significantly increased. These results suggest that PQQ treatment can improve the early embryonic development potential of PCOS mice.

[0079] Example 6 PQQ supplementation can shorten the time to first litter birth in PCOS mice

[0080] The experimental method is as follows: 2-4 month old male mice with confirmed fertility were caged with female mice from each group at a ratio of 1:2 until delivery, and the time from caged to the delivery of the first litter was recorded.

[0081] Figure 7 The results showed that compared with the control group, the time to birth of the first litter of mice in the DHEA group was significantly prolonged, while supplementation with PQQ could shorten the time to birth of the first litter.

[0082] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. Use of pyrroloquinoline quinone or a pyrroloquinoline quinone salt in the preparation of a product for treating and / or improving polycystic ovary syndrome.

2. The use according to claim 1, characterized in that The treatment and / or improvement of polycystic ovary syndrome includes improving the ovulation function and enhancing the fertility of patients with polycystic ovary syndrome.

3. The use according to claim 2, characterized in that The pyrroloquinoline quinone or pyrroloquinoline quinone salt improves the ovulation function and fertility of patients with polycystic ovary syndrome by one or more of the following ways: 1) Improve the polycystic ovarian morphology of PCOS patients; II) Improve the imbalance of sex hormone secretion in PCOS patients; III) Adjust the estrus cycle of PCOS patients; IV), improve glucose metabolism in PCOS patients; V) Improve ovarian fibrosis in PCOS patients; VI), promoting oocyte maturation in PCOS patients; VII) Enhance the early embryonic development potential and promote pregnancy in PCOS patients.

4. The use according to claim 3, characterized in that The improvement of the polycystic ovarian morphology of PCOS patients is to restore the normal morphology of the ovaries and place the follicles in the ovaries in different developmental stages.

5. The use according to claim 3, characterized in that The improving the sex hormone secretion disorder of PCOS patients is to reduce the testosterone level in serum.

6. The use according to claim 3, characterized in that The adjusting of the estrus cycle of PCOS patients is to make the estrus cycle regular.

7. The use according to claim 3, characterized in that The improving of glucose metabolism in PCOS patients includes improving glucose tolerance, insulin tolerance and / or reducing body weight.

8. The use according to claim 3, characterized in that The improvement of ovarian fibrosis in PCOS patients includes reducing the proportion of picrosirius red staining-positive area in ovarian tissue and reducing the expression levels of fibrosis-related molecules in ovarian tissue.

9. The use according to claim 8, characterized in that The ovarian tissue fibrosis-related molecules include CTGF, TGFβ and / or PPARγ.

10. The use according to claim 3, characterized in that The promoting oocyte maturation of PCOS patients includes reducing the abnormality rate of meiotic spindle in MII oocytes of PCOS patients and / or promoting the discharge of the first polar body.

11. The use according to claim 3, characterized in that The enhancing of the early embryonic development potential of PCOS patients includes enhancing the 4-cell formation rate and / or the blastocyst formation rate, and the promoting of pregnancy is to shorten the time of first birth.

12. The use according to claim 1, characterized in that The dosage form of the product is selected from one or more of tablets, capsules, oral liquids, buccal preparations, granules, fat emulsions, microcapsules, dripping pills, granules, pills, powders, ointments, pills, suspensions, powders, and solutions.

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