Use of stromal cell-derived factor 1 in preparation of drugs for preventing and treating ovarian aging

Abstract

The present application relates to the technical field of biological medicine, and more particularly to application of stromal cell-derived factor 1 in preparation of medicines for preventing and treating ovarian aging. By supplementing SDF-1 in the body of old mice, the results show that supplementing SDF-1 in the body can significantly improve the ovarian function and reproductive capacity of old mice in multiple key indicators, revealing the great potential of SDF-1 in delaying ovarian aging and improving reproductive outcomes, providing a new drug target and preparation scheme for improving the reproductive capacity of old women and improving the success rate of assisted reproductive technology, and having important clinical application value.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to the application of stromal cell-derived factor 1 in the preparation of drugs for preventing and treating ovarian aging. Background Technology

[0002] Age-related decline in female fertility is a significant clinical challenge in reproductive medicine. While assisted reproductive technologies (ART) offer a pathway to pregnancy, their effectiveness is heavily influenced by the mother's age. Live birth rates after in-vitro fertilization (IVF) are reported to exceed 40% in women under 35, but drop sharply to only 1-2% by age 44. This reproductive aging is largely attributed to reduced ovarian reserve and decreased oocyte quality, often accompanied by increased aneuploidy. Although preclinical interventions such as nicotinamide mononucleotide (NMN) supplementation have shown promise in alleviating these deficiencies in animal models, the search for more potential treatment strategies remains an urgent research priority.

[0003] Currently, the most common drugs used in clinical practice to treat ovarian aging are antioxidants, such as melatonin, vitamin E, and coenzyme Q10. These drugs help improve ovarian function by reducing ROS levels, protecting mitochondria, and promoting DNA damage repair, which is beneficial for oocyte and embryonic development. In addition, DHEA, GH, anticoagulants (aspirin, low molecular weight heparin), immunosuppressants (glucocorticoids, tacrolimus, sirolimus, etc.), traditional Chinese medicine, and stem cells have all been reported for the treatment of ovarian aging.

[0004] Stromal cell-derived factor-1 (SDF-1), also known as CXC motif chemokine 12 (CXCL12), is a multifunctional cytokine known to regulate various cellular processes, including antioxidant defense, migration, proliferation, and differentiation, in multiple cell types. Current research on local injection of SDF-1 in vivo mainly focuses on neurological and orthopedic diseases, emphasizing the mechanism of action of SDF-1 as a chemokine in disease development. However, research on reproductive system diseases remains relatively weak, particularly regarding the effects of SDF-1 supplementation on ovarian function and oocyte quality in older female animals, where systematic experimental evidence and in-depth exploration are still lacking. Summary of the Invention

[0005] In view of this, the present invention proposes the application of stromal cell-derived factor 1 (SDF-1) in the preparation of drugs for preventing and treating ovarian aging. Supplementation of aged mice with SDF-1 showed that in vivo supplementation significantly improved ovarian function and reproductive capacity in aged mice across multiple key indicators, revealing the great potential of SDF-1 in delaying ovarian aging and improving reproductive outcomes.

[0006] The technical solution of this invention is implemented as follows: In a first aspect, the present invention provides the application of stromal cell-derived factor 1 in the preparation of drugs for preventing and treating ovarian aging.

[0007] Based on the above technical solutions, preferably, the drug is a drug used to treat one or more of the following: decreased ovarian function, reduced number of follicles, decreased quality of oocytes, or reduced embryonic developmental potential.

[0008] Based on the above technical solutions, preferably, the drug includes an injectable form.

[0009] Based on the above technical solutions, preferably, the unit dose of stromal cell-derived factor 1 in the injection is 10~100μg.

[0010] Secondly, a drug for preventing and treating ovarian aging is provided, comprising stromal cell-derived factor 1 and a pharmaceutically acceptable carrier.

[0011] The application of the stromal cell-derived factor 1 of the present invention in the preparation of drugs for preventing and treating ovarian aging has the following advantages over the prior art: 1. This invention discovers and confirms that stromal cell-derived factor 1 (SDF-1) can be used to prepare drugs for preventing and treating ovarian aging. Clinical sample testing revealed that the SDF-1 content in the follicular fluid of older women was significantly lower than that of younger women, and that SDF-1 levels were negatively correlated with age and positively correlated with antral follicle count, suggesting a close relationship between SDF-1 and ovarian aging. Based on this, this invention systematically verified the effect of SDF-1 on improving the quality of oocytes in older women through in vivo experiments, providing a novel direction for the application of SDF-1 in the field of reproductive aging.

[0012] 2. Intraperitoneal injection of SDF-1 significantly improved ovarian function and oocyte quality in older female mice, specifically by improving ovarian reserve, increasing the number and quality of oocytes, improving nuclear maturation, enhancing mitochondrial function, reducing oxidative stress, and improving fertilization capacity and embryonic development potential.

[0013] 3. SDF-1 is an endogenous small molecule chemokine with good biocompatibility and low immunogenicity. In vivo experiments have demonstrated that, within the effective dosage range, SDF-1 significantly improves oocyte and embryonic development without obvious toxic side effects. Furthermore, SDF-1 can be recombinantly expressed and purified using existing biotechnological methods, making production costs controllable and showing promising prospects for clinical translation. Attached Figure Description

[0014] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0015] Figure 1 Correlation diagram of SDF-1 content in follicular fluid and various clinical parameters in women in Example 1 of the present invention; Figure 2 A comparison of SDF-1 content in follicular fluid between young and elderly patients in Example 1 of this invention; Figure 3 The figures shown are ovarian volume and ovarian index of the young group, the older group, and the older drug administration group in Example 2 of the present invention. Figure (A) shows the ovarian volume and Figure (B) shows the ovarian index. Young: young group, Aged: older group, SDF-1+Aged: older drug administration group. Figure 4 The images show HE staining and follicle counting of ovarian sections from mice in the young group, older group, and older drug-treated group in Example 2 of the present invention. Image (A) shows a representative image of a mouse ovarian section, with scale bars: a=500μm, b=250μm. Image (B) shows the number of follicles at different developmental stages in each ovarian section. Figure 5 The figures in Example 2 of this invention show the DNA damage in the ovaries of mice in the young group, older group, and older drug administration group. Figure (A) shows a representative image of γH2AX immunohistochemical staining of mouse ovarian sections. Scale bar: a=250 μm, b=100 μm. Figure (B) shows a statistical chart of the proportion of γH2AX positive cells among the groups. Figure 6 The following diagram illustrates the effect of SDF-1 on the in vivo maturation of oocytes in older mice in Example 2 of this invention. Figure (A) shows a schematic diagram of mature oocytes in each group, with scale bars: a=50 μm, b=30 μm. Figure (B) shows the number of oocytes retrieved after ovulation induction in each group. Figure (C) shows the oocyte maturation rate after ovulation induction in each group. Figure (D) shows the oocyte fragmentation rate after ovulation induction in each group. Figure 7 The following is a diagram showing the effect of in vivo SDF-1 supplementation on the spindle and chromosome morphology of oocytes in aged mice in Example 2 of the present invention. In the diagram, (A) shows the fluorescence staining of spindle and chromosome in each group, with green fluorescence representing spindle and blue fluorescence representing chromosome. Scale bar: 25 μm. (B) shows the statistical diagram of the proportion of abnormal chromosome arrangement in each group. (C) shows the statistical diagram of the proportion of abnormal spindle morphology in each group. Figure 8 The figure shows the effect of SDF-1 on the mitochondrial function of mature oocytes in elderly mouse oocytes in Example 2 of the present invention. Figure (A) shows the mitochondrial fluorescence staining between groups, scale bar: 50 μm, and Figure (B) shows the fluorescence intensity statistics between groups. Figure 9 The figure shows the effect of SDF-1 on the ROS level of mature oocytes in vivo from aged mice in Example 2 of the present invention. Figure (A) shows the ROS fluorescence of oocytes in vivo in each group, scale bar: 20 μm, and Figure (B) shows the statistical graph of ROS levels among different groups. Figure 10 The diagram shows the effect of SDF-1 on the cortical granules of mature oocytes in elderly mice in Example 2 of the present invention. In the diagram (A), the LCA fluorescence staining of mature oocytes in the young group, the elderly group and the elderly drug-treated group is shown. The scale bar is 20 μm. The diagram (B) shows the statistical diagram of LCA fluorescence intensity among the groups. Figure 11 The figure shows the effect of in vivo SDF-1 supplementation on the sperm-egg binding level of oocytes in elderly mice in Example 2 of the present invention. Figure (A) shows the sperm-egg binding fluorescence staining in each group, scale bar: 20 μm, and Figure (B) shows the statistical diagram of the number of sperm bound to each oocyte in each group. Figure 12 The diagram shows the effect of SDF-1 on the in vivo IVF outcome of mature oocytes in elderly mice in Example 2 of the present invention. Figure (A) shows the schematic diagram of the two-cell and blastocyst stages of IVF in mice in the young group, the elderly group, and the elderly drug-treated group. Scale bar: 100 μm. Figure (B) shows the statistical graph of fertilization rate, cleavage rate and blastocyst formation rate among the groups. Detailed Implementation

[0016] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0017] Clinical Sample Collection: Follicular fluid and immature oocytes in this invention were obtained from patients undergoing IVF treatment at the Reproductive Medicine Center of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (Wuhan, China). All participants provided informed consent for the donation of these materials for research purposes, and this invention was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-IRB202410032). Patients diagnosed with tubal or male factor infertility were included. Exclusion criteria included endometriosis, adenomyosis, tumors, chromosomal abnormalities, or other complications. Controlled ovarian stimulation (COH) was performed according to a known standard protocol. After oocyte retrieval, follicular fluid was examined under a stereomicroscope to identify and obtain the cumulus-oocyte complex. After removing cumulus cells, immature oocytes were collected and fixed with 4% paraformaldehyde for subsequent fluorescent staining. The retained follicular fluid was collected and centrifuged at 1500×g for 20 minutes. The resulting follicular supernatant was then transferred to test tubes and stored at -80°C for subsequent SDF-1 concentration detection.

[0018] All animal experimental protocols used in this invention were approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJH-202312019). The 6-8 week old young female ICR mice, 44-48 week old older female ICR mice, and 10 week old male ICR mice used were all SPF-grade animals purchased from Shulaibao (Wuhan) Biotechnology Co., Ltd. The mice were raised at the Animal Experiment Center of the inventor's research building and have been approved by the hospital's Animal Ethics Committee.

[0019] The SDF-1 recombinant protein used in this invention was purchased from Wuhan Aiboteke Biotechnology Co., Ltd., and the other reagents were all commercially available products.

[0020] Example 1: Correlation analysis of SDF-1 content in follicular fluid of human population Whether SDF-1 levels differ among different populations in follicular fluid, whether its concentration is correlated with clinical parameters such as age, body mass index (BMI), antral follicle count (AFC), and various hormone levels, and whether SDF-1 participates in oocyte development and maturation—these questions remain unanswered. Therefore, this study will first measure the SDF-1 concentration in collected follicular fluid, analyze the correlation between SDF-1 levels and clinical parameters such as age, BMI, AFC, and various hormone levels, and then group the included women according to age to analyze the differences in SDF-1 levels between the two groups, comparing the laboratory indicators and clinical outcomes between the two groups.

[0021] This study collected discarded follicular fluid samples from 182 female patients who underwent assisted reproductive technology at our Reproductive Medicine Center and met the inclusion and exclusion criteria. To investigate the correlation between SDF-1 levels in follicular fluid and various clinical parameters of the female patients, we used an ELISA kit to detect SDF-1 concentration in follicular fluid and analyzed it using Spearman correlation analysis. The results indicated that SDF-1 levels in follicular fluid were negatively correlated with female age (r=-0.528, P<0.001) and positively correlated with female AFC (r=0.182, P=0.014), both showing statistically significant differences. However, no significant correlations were found between SDF-1 levels in follicular fluid and female BMI (r=-0.142, P=0.055), endometrial thickness on the day of hCG administration (r=0.120, P=0.106), anti-müllerian hormone (AMH) (r=0.075, P=0.311), and basal FSH (r=-0.034, P=0.649). Figure 1 (As shown).

[0022] The aforementioned results suggest a negative correlation between SDF-1 levels in follicular fluid and female age. Therefore, we grouped the 182 collected discarded follicular fluid samples according to age: 77 cases in the advanced age group (≥35 years) and 105 cases in the younger age group (<35 years). The clinical baseline differences between the two groups are shown in Table 1. The basal FSH, AFC, and AMH levels in the advanced age group were significantly lower than those in the younger group (P<0.05), and the proportion of secondary infertility and female factor infertility was significantly higher in the advanced age group (P<0.05). Furthermore, there were no statistically significant differences in BMI and duration of infertility between the two groups.

[0023] Table 1. Clinical baseline characteristics of patients in the elderly and younger groups.

[0024] The results of the difference in SDF-1 content in follicular fluid between the older and younger groups are as follows: Figure 2 As shown, the SDF-1 content in the follicular fluid of older patients was significantly lower than that of younger patients (4861.8±26.2 pg / mL vs. 4410.3±19.7 pg / mL), which was statistically significant (P<0.001).

[0025] Based on the results of this embodiment, the SDF-1 content in the follicular fluid of older women was lower than that in younger women, suggesting that SDF-1 may have a beneficial effect on oocyte quality or ovarian reserve function. Therefore, in subsequent experiments, we will attempt to supplement older mice with SDF-1 in vivo and observe the effects of SDF-1 on ovarian function, oocyte quality, and subsequent development in older mice.

[0026] Example 2: Study on the effect of in vivo SDF-1 supplementation on oocyte quality in aged mice 1. Intraperitoneal injection of SDF-1 into mice.

[0027] Experimental groupings and animals used in this embodiment: ①Young group: 6-8 week old young female ICR mice (n=6); ②Aged group: 44-48 week old female ICR mice (n=6); ③Aged drug-treated group (SDF-1+ Aged): 44-48 week old female ICR mice (n=6).

[0028] The SDF-1 recombinant protein powder was dissolved in PBS, aliquoted, and frozen at -80°C. Before injection, the aliquoted SDF-1 solution was taken out, diluted with physiological saline, and administered intraperitoneally to group ③ at a dose of 10 μg / kg mouse body weight. Groups ① and ② were injected intraperitoneally with the same amount of physiological saline. All three groups were injected continuously for 14 days before subsequent experiments.

[0029] Fourteen days after intraperitoneal injection, mice were sacrificed, and their ovaries were removed for weighing, photographing, and ovarian index calculation. The results showed (e.g.) Figure 1 As shown in the figure: the ovarian volume of older mice was significantly smaller than that of younger mice, and the ovarian index was significantly lower (0.027±0.002‰ vs. 0.038±0.002‰, P=0.0005). After intraperitoneal injection of SDF-1, the ovarian volume of older mice increased, and the ovarian index significantly increased to 0.038±0.001‰ (P=0.0002), approaching the level of younger mice.

[0030] According to the above-mentioned study, intraperitoneal injection of SDF-1 at a dose of 10 μg / kg body weight for 14 consecutive days significantly improved ovarian function in aged mice. Using the body surface area normalization method for interspecies dose conversion, the mouse dose needs to be divided by approximately 12.3 to convert to the human equivalent dose (HED), meaning a 10 μg / kg mouse dose is equivalent to approximately 0.8 μg / kg human dose. Based on an average adult body weight of 60 kg, the single-dose dose is approximately 48 μg. Considering individual differences, formulation stability, and clinical ease of use, the unit dose range for the human injectable is determined to be 10 μg-100 μg, which adequately covers the clinically effective dose requirements.

[0031] 2. Ovarian tissue sampling and processing, ovarian section HE staining and follicle counting.

[0032] After the last administration, mice were sacrificed by cervical dislocation, and both ovaries were harvested. One ovary was weighed, and the ovarian index was calculated (ovarian index = weight of one ovary / mouse body weight × 1000‰); the other ovary was fixed in 4% paraformaldehyde for 24 hours using standard methods, dehydrated with graded ethanol, embedded in paraffin, and sectioned.

[0033] Sections were routinely dewaxed, stained with hematoxylin for 5 minutes, differentiated, blued, and stained with eosin for 5 minutes. After dehydration and mounting, follicles at different developmental stages were observed and counted under a light microscope. Follicle classification criteria: primordial follicle (PmF), primary follicle (PF), secondary follicle (SF), preantral follicle (PAF), and antral follicle (AF).

[0034] Results of ovarian section HE staining and follicle count (e.g.) Figure 2 As shown in the figure): the number of all types of follicles in older mice was significantly lower than that in younger mice (PmF: 142.6±4.5 vs. 1019.2±19.1, P<0.0001; PF: 37.0±1.5 vs. 143.4±3.7, P<0.0001; SF: 20.2±1.5 vs. 91.2±2.2, P<0.0001; PAF: 11.8±0.9 vs. 56.6±1.7, P<0.0001; AF: 2.6±0.5 vs. 14.8±1.7, P=0.0003). After intraperitoneal injection of SDF-1, the number of PmF, PF, and SF in older mice was slightly increased compared with that in untreated older mice, but the difference was not statistically significant, while PAF and AF were significantly increased (PAF: 16.8±0.9 vs. 14.8±1.7, P=0.0003). 11.8±0.9, P=0.0065; AF: 6.2±0.6 vs. 2.6±0.5, P=0.0026).

[0035] 3. Immunohistochemical detection of ovarian damage.

[0036] After dewaxing, the sections underwent antigen retrieval, elimination of endogenous peroxidase with 3% H2O2, blocking with goat serum, and incubation with γH2AX primary antibody overnight at 4°C. They were then incubated with HRP-labeled secondary antibody at room temperature for 1 hour, developed with DAB, counterstained with hematoxylin, and dehydrated and mounted. The entire slide was scanned, and the proportion of γH2AX-positive cells was analyzed.

[0037] The expression of γH2AX, an ovarian injury marker, in different groups of mice was observed by immunohistochemical staining. Figure 3The results showed that the proportion of γH2AX positive cells in older mice was significantly higher than that in younger mice (54.5±5.2% vs. 26.8±0.9%, P=0.0008). The proportion of γH2AX positive cells in the older mice treated with the drug was significantly reduced (33.0±1.1% vs. 54.5±5.2%, P=0.0038), but it was still higher than that in the younger mice.

[0038] 4. Effects of SDF-1 administration on in vivo maturation capacity and ovarian reserve of oocytes in older mice.

[0039] (1) Ovulation induction and oocyte collection in mice.

[0040] On the first day, female mice were intraperitoneally injected with PMSG (10 IU / mouse) at 7 PM, followed by hCG (10 IU / mouse) 48 hours later. 14-16 hours after hCG injection, the mice were euthanized. Both fallopian tubes were placed in mineral oil in a hyaluronidase degranulation dish. Under a stereomicroscope, the ampulla of the fallopian tube was incised using two 1 mL syringe needles to release COCs (cumulus-oocyte complexes). The COCs were then drawn into a droplet of hyaluronidase using a syringe. The oocytes were repeatedly agitated with a glass pipette for approximately 2-3 minutes until the granulosa cells loosened. The naked oocytes were then transferred to an adjacent M2 droplet and agitated repeatedly until the granulosa cells were completely detached. The naked oocytes were then repeatedly washed in M2 culture medium droplets to remove hyaluronidase. The number of ovulation-inducing eggs, oocyte maturation rate (number of mature oocytes / total number of oocytes), and fragmentation rate (number of fragmented oocytes / total number of oocytes) were recorded.

[0041] Oocytes were collected from aged mice after ovulation induction, and their counts and morphological evaluations were performed. The results are as follows: Figure 4As shown: Ovulation induction was performed on three groups of mice. The number of oocytes retrieved from the older group was significantly lower than that from the younger group (19.8±1.3 vs. 37.6±1.8, P<0.0001). After drug administration, the number of oocytes retrieved from the older group was significantly higher (24.5±1.2 vs. 19.8±1.3, P=0.0178). Among the oocytes retrieved after ovulation induction, the maturation rate of oocytes from the younger group was significantly higher than that from the older group (80.6±1.2% vs. 58.3±1.4%, P<0.0001). Intraperitoneal administration improved the maturation rate of ovulation-inducing oocytes (70.5±1.1% vs. 58.3±1.4%, P<0.0001). Regarding oocyte fragmentation rate, the fragmentation rate of oocytes stimulated in young mice was approximately 3.9±0.5%, while the fragmentation rate of older mice increased significantly to approximately 22.1±0.8%, with a statistically significant difference between the two groups (P<0.0001). After administration, the fragmentation rate of older mice was significantly lower than that of the unadministered group (13.2±2.0% vs. 22.1±0.8%, P=0.0012), but it was still higher than that of young mice (P=0.0005).

[0042] We further evaluated the effect of in vivo SDF-1 administration on the quality of mature oocytes in aged mice, such as... Figure 5 As shown, the proportion of abnormal spindle morphology in older mice was significantly higher than that in younger mice (23.3±1.4% vs. 11.8±0.9%, P=0.002). After drug administration, the proportion of abnormal spindle morphology in older mice decreased, showing a statistically significant difference (17.5±0.6% vs. 23.3±1.4%, P=0.018). The trend of abnormal chromosome arrangement proportion was consistent with that of spindle morphology. The proportion of abnormal chromosomes in younger mice was approximately 4.2±1.2%, while the proportion in older mice was significantly higher than that in younger mice (9.2±0.5%, P=0.018). After drug administration, the proportion of abnormal chromosomes in older mice decreased (6.7±0.2%), showing a significant difference (P=0.012). This indicates that SDF-1 can improve the quality of oocytes in older mice.

[0043] The mitochondrial function of three groups of mature oocytes was assessed (e.g. Figure 6 As shown in the figure, the mitochondrial fluorescence intensity of oocytes in the young group was significantly higher than that in the older group (88.18±8.6 vs. 17.7±1.0, P<0.0001), while the mitochondrial fluorescence intensity of older mice after intraperitoneal administration was higher than that in the unadministered group (54.5±3.4 vs. 17.7±1.0, P<0.0001), but still did not reach the level of the young group.

[0044] Subsequently, the ROS levels of each group were measured, such as... Figure 7As shown, the ROS level in the younger group was significantly lower than that in the older group (9.6±0.9 vs. 15.5±1.7, P=0.011), and intraperitoneal administration significantly reduced the ROS level in mature oocytes of older mice (7.8±0.8 vs. 15.5±1.7, P=0.001), bringing it close to the level in the younger group.

[0045] 5. Effects of SDF-1 on fertilization capacity and developmental potential in older mice.

[0046] The cytoplasmic maturation of oocytes, which is closely related to fertilization capacity, was detected using conventional methods (results are shown below). Figure 8 As shown in the figure, the fluorescence intensity of cortical granules in oocytes of the young group was significantly higher than that of the old group (10.6±1.9 vs. 2.9±0.7, P=0.002). SDF-1 administration could partially increase the fluorescence intensity of cortical granules in old mice, which was statistically significant (5.7±0.9 vs. 2.9±0.7, P=0.025).

[0047] The effect of SDF-1 on sperm-egg binding during IVF was also examined, such as... Figure 9 As shown, the number of sperm fertilized per oocyte in young mice was approximately 260.4 ± 19.3, while this number decreased significantly in older mice to approximately 49.4 ± 3.4, with a statistically significant difference between the two groups (P < 0.0001). After in vivo administration, the number of sperm fertilized in older mice increased to 77.5 ± 4.3, and compared with untreated older mice, SDF-1 could increase the number of sperm fertilized in older mice to a certain extent (P < 0.0001).

[0048] Simultaneously, the IVF-related indicators of each group were statistically analyzed to explore the effect of SDF-1 in vivo administration on IVF outcomes in aged mice. The results are as follows: Figure 10 As shown, the fertilization rate, cleavage rate, and blastocyst formation rate of young mice were all higher than those of older mice, with statistically significant differences. In vivo administration can improve the fertilization rate, cleavage rate, and blastocyst formation rate of older mice to a certain extent, thus improving the IVF outcome of older mice.

[0049] In this embodiment, we supplemented aged mice with SDF-1, hoping to improve ovarian function and oocyte quality by increasing the concentration of SDF-1 in the ovarian microenvironment. Results showed that SDF-1 can improve ovarian function and oocyte quality in aged mice, enhance oocyte fertilization capacity and subsequent embryonic development, thereby improving the fertility of aged mice. This embodiment focuses on the antioxidant function of SDF-1, applying it to aged mice via intraperitoneal injection. The results showed that ovarian function in aged mice was significantly improved in several aspects: ovarian index was significantly increased, the number of follicles at each stage increased, and the level of ovarian damage decreased. Furthermore, the ovulation induction effect was significantly enhanced, manifested in increased oocyte number, reduced fragmentation rate, and improved maturation rate. Oocyte quality was also significantly improved, specifically manifested in reduced abnormal spindle morphology rate and chromosome alignment rate, enhanced mitochondrial activity, and reduced ROS levels. The fertilization capacity of older mice in the drug-treated group was significantly improved, as evidenced by an increase in the number of sperm-egg combinations and elevated levels of cortical granules. The subsequent embryonic development potential of older mice was also improved, with significantly increased fertilization rate, cleavage rate, and blastocyst formation rate.

[0050] In summary, the results of this study suggest that in vivo SDF-1 supplementation can significantly improve ovarian function and reproductive capacity in aged mice across multiple key indicators, revealing the significant potential of SDF-1 in delaying ovarian aging and improving reproductive outcomes. These findings not only provide a new perspective for understanding the mechanisms of ovarian aging but also offer strong theoretical support for developing clinical intervention strategies targeting fertility issues in older women.

[0051] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. The application of a stromal cell-derived factor 1 in the preparation of drugs for preventing and treating ovarian aging.

2. The application as described in claim 1, characterized in that, The drug is used to treat one or more of the following: decreased ovarian function, reduced number of follicles, decreased oocyte quality, or reduced embryonic developmental potential.

3. The application as described in claim 1, characterized in that: The medications mentioned include injectable forms.

4. The application as described in claim 3, characterized in that: The unit dose of stromal cell-derived factor 1 in the aforementioned injection is 10~100μg.

5. A drug for preventing and treating ovarian aging, characterized in that: It contains stromal cell-derived factor 1 and a pharmaceutically acceptable carrier.

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