CN111686101A - Application of sulforaphane in improving reproductive performance of mammals - Google Patents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/26—Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
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- Chemical Kinetics & Catalysis (AREA)
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- Gynecology & Obstetrics (AREA)
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Abstract
The invention relates to an application of sulforaphane in improving the reproductive performance of mammals, which can promote the proliferation and the activity of in vitro granular cells and inhibit the apoptosis of the granular cells by utilizing the sulforaphane. Sulforaphane promotes the production of estradiol and the expression of steroid synthase genes such as granulosa cells StAR and CYP19A1 in vitro. Sulforaphane promotes the expression of the FSH receptor of granulosa cells in vitro. Sulforaphane promotes development of mouse ovary and increases weight of ovary. Sulforaphane promotes the proliferation of granulosa cells in vivo. The sulforaphane promotes the development of ovarian follicles of mice, increases the number of the follicles and increases the number of ovulations. The daily ration of the weaned sow added with the sulforaphen obviously improves the litter size of the sow. The invention provides a new application of the sulforaphane, greatly improves the application value of the sulforaphane, enlarges the application range of the sulforaphane, expands the new field of the sulforaphane, and has wide application prospect and commercial value.
Description
Technical Field
The invention belongs to the technical field of reproductive biology, and particularly relates to application of sulforaphane in improving reproductive performance of mammals.
Background
The reproduction is the root of the continuation of the human generation, unfortunately, the reproduction disorder of the human beings in the current society occurs frequently, and about 10 percent of couples are troubled by the reproduction disorder according to statistics; on the other hand, the reproductive performance of livestock is an important economic character, and the improvement of the double-lamb rate of livestock such as beef cattle, sheep and the like and the increase of the litter size of sows (shortening the gap with developed countries) have great significance for improving the quality and the efficiency of the animal husbandry. Therefore, the research and development of a new technology for safely and efficiently improving the reproductive performance of mammals not only has great practical requirements, but also has great application value and commercial prospect.
The ovary is the most important reproductive organ of female animals, and the function of the ovary is mainly to produce ovum and steroid hormone. Ovarian follicle growth and development are the physiological basis for oestrus and ovulation in dams. Granulosa cells are the main components of follicles except oocytes in follicles, and the regulation of the growth and development of oocytes by the production of steroid hormones (e.g., estradiol and progesterone) and the secretion of Stem Cell Factor (SCF) is an important function of granulosa cells (Yada H et al, 1999). During the development of the follicle, granulosa cells are continuously proliferated and differentiated, and are expressed as morphological change and increase of the number of cells and the number of layers; at the same time, the granulosa cells have an increasing capacity for steroid hormone synthesis. Follicular development is mainly regulated by Follicle Stimulating Hormone (FSH), which promotes cell proliferation and steroid hormone production via granulosa cell membrane receptors (Yu FQ et al, 2005). FSH is considered to be the most important regulator of follicular growth and development. It is known that exogenous administration of FSH is effective in promoting ovulation and that techniques for superovulation in various domestic animals including pigs have been established using this principle, but these techniques have the disadvantages of high cost, influence on hormone balance and embryo attachment, etc. The applicant finds that the plant-derived small molecular compound-Sulforaphane (SFN) can remarkably promote the proliferation of porcine follicular granular cells and mouse follicular granular cells, and surprisingly, the promoting effect of the SFN on the proliferation of the porcine follicular granular cells is better than that of FSH, and the expression of steroid synthase genes such as StAR, CYP19A1 (similar to FSH) is remarkably promoted, so that the possibility of improving the reproductive performance of female animals by utilizing the SFN is provided.
Sulforaphane (1-isothiocyanato-4-methylsulfonylbutane, SFN), also known as sulforaphane, is an isothiocyanate produced from glucosinolates by myrosinase hydrolysis in plants, and is widely found in cruciferous plants, such as broccoli, cabbage, cauliflower, and the like. Sulforaphane is a sulfur-containing compound with molecular formula of C6H11S2NO, with a relative molecular mass of 177.29, is a yellow or colorless liquid at room temperature, is insoluble in water, is very soluble in organic solvents, and is easy to absorb. A large number of research reports prove that sulforaphane has the functions of resisting oxidation, tumors and inflammation, regulating epigenetic modification and the like (Li H et al, 2018; Byrne MM et al, 2014). It has been shown that ingestion of sulforaphane-rich cruciferous vegetables is beneficial for health, including prevention of many diseases such as cardiovascular diseases, neurodegenerative diseases and diabetes. In terms of tumor prevention, sulforaphane can reduce the risk of many types of tumors, such as colorectal cancer, renal cancer, breast cancer, and the like. Regulating and controlling cell proliferation and differentiation are important ways for SFN to play a role, the concentration and cell type of the SFN influence the regulating and controlling effect of the SFN on cell proliferation and differentiation, for example, Han et al (Han Z et al, 2017) find that low-concentration sulforaphane can promote the proliferation of neural stem cells and remarkably promote the differentiation of neurons, so that the effect of preventing neurodegenerative diseases is achieved; in contrast, sulforaphane has the effects of inhibiting the proliferation of different types of cancer cells, inducing cell cycle arrest of the cancer cells, promoting cancer cell apoptosis and the like (Bryant CS et al, 2010; Chaudhuri D et al, 2007; Ashok BT et al, 2005).
The present invention related to sulforaphane focuses on its extraction and preparation technology, such as a preparation method for extracting sulforaphane from broccoli (CN105949098A), a sulforaphane extraction process (CN108048498A), a sulforaphane extraction method (CN108912024A), a sulforaphane microcapsule preparation method (CN107569470A), a sulforaphane inclusion compound preparation method (CN108992675A), a sulforaphane health tablet preparation method (CN106214721A), and the like. In the application aspect of the sulforaphane, patents focusing on the protection effect of the sulforaphane on adult health are mostly focused, and no patents for promoting the reproductive performance of mammals exist, such as the application of the sulforaphane in telomerase activity inhibition and preparation of anti-cancer drugs (CN109771409A), the application of the sulforaphane in preparation of foods, health care products or medicines for preventing diabetic lesions (CN108743576A), the application of the sulforaphane in preparation of drugs for protecting the fetal vascular development of women drinking wine during pregnancy (CN108771669B) and the like.
Disclosure of Invention
The technical problem to be solved is as follows: the invention provides an application of sulforaphane in improving the reproductive performance of mammals in order to improve the reproductive capacity of the mammals. The sulforaphane is adopted to remarkably promote the proliferation of follicular granular cells of pigs and mice and the synthesis of steroid hormones, and more importantly, the sulforaphane with a certain concentration can promote the ovarian weight gain of the mice, the follicular development and ovulation of the mice and the litter size of sows.
The technical scheme is as follows: application of sulforaphane and its derivatives in preparing product for improving mammal reproductive performance is provided.
Application of sulforaphane and derivatives thereof in preparing mature products for promoting follicular granulosa cell proliferation.
Application of sulforaphane and derivatives thereof in preparing products for promoting ovarian follicle development.
Application of sulforaphane and derivatives thereof in preparing products for promoting estrus and ovulation.
The effective concentration of the sulforaphane is as follows: not higher than 10 μ M in vitro and not higher than 5mg/kg in vivo.
The effective concentration of the sulforaphane is as follows: 1-10 μ M in vitro and 0.1-5 mg/kg in vivo.
The Sulforaphane (SFN) has the molecular formula of C6H11S2NO, relative molecular mass 177.29.
Has the advantages that: the sulforaphane promotes the proliferation and the activity of in vitro granular cells and inhibits the apoptosis of the granular cells. Sulforaphane promotes the production of estradiol and the expression of steroid synthase genes such as granulosa cells StAR and CYP19A1 in vitro. Sulforaphane promotes the expression of the FSH receptor of granulosa cells in vitro. Sulforaphane promotes development of mouse ovary and increases weight of ovary. Sulforaphane promotes the proliferation of granulosa cells in vivo. The sulforaphane promotes the development of ovarian follicles of mice, increases the number of the follicles and increases the number of ovulations. The daily ration of the weaned sow added with the sulforaphen obviously improves the litter size of the sow. The invention provides a new application of the sulforaphane, greatly improves the application value of the sulforaphane, enlarges the application range of the sulforaphane, expands the new field of the sulforaphane, and has wide application prospect and commercial value.
Drawings
FIG. 1 is a graph showing that sulforaphane promotes the proliferation and viability of granulosa cells in vitro and inhibits apoptosis of the granulosa cells in example 1 of the present invention. In the figure, A: after the in vitro culture granular cells of the pigs and the mice are treated by adding the sulforaphane for 24 hours, the activity level of the cells is detected by CCK-8. B: after the granular cells cultured in vitro of the pigs and the mice are added with the sulforaphane for treatment for 12h, the granular cells are doped with EdU for incubation for 2h, and then the granular cells are observed and photographed under a laser confocal microscope, the level of the EdU staining marker of the granular cells is detected, and the proportion of positive cells is quantitatively analyzed. C: after the granular cells cultured in vitro of pigs and mice are treated by adding sulforaphane for 12 hours, the expression level and the gray level of PCNA protein of the granular cells are detected by western blot. D: adding sulforaphane into the mouse in vitro cultured granular cells, and detecting the expression level and gray level analysis of the granular cell clean-caspase 3 protein by using western blot after 12 hours. The results of the above corresponding experiments are expressed as mean ± sem, # P <0.05, # P <0.01, # P <0.001, # P <0.0001, ns, not significant, P > 0.05.
FIG. 2 is a graph showing the in vitro promotion of estradiol production by sulforaphane and the expression of steroid synthase genes such as granulosa cells StAR and CYP19A1 in example 2 of the present invention. In the figure, A: ELISA was used to detect changes in estrogen levels in the supernatants of granular cell cultures from control and sulforaphane mice. P < 0.05. B: after the mouse granular cells are treated by the sulforaphane for 12 hours, the mRNA level change of the steroid hormone synthetase gene is detected by fluorescent quantitative PCR, and the expression quantity of the related gene is calculated by taking beta-actin as an internal reference. C: after the mouse granular cells are treated by sulforaphane for 12 hours, Western blot is used for detecting the protein level change of the steroid hormone synthetase gene and carrying out gray level analysis. The results of the above corresponding experiments are expressed as mean ± sem, # P <0.05, # P <0.01, # P <0.001, # P <0.0001, ns, not significant, P > 0.05.
FIG. 3 is a graph showing the enhancement of in vitro granulosa cell FSH receptor expression by sulforaphane in example 3 of the present invention. After the mouse granular cells are treated by sulforaphane for 12 hours, Western blot is used for detecting the level change of FSHR protein of an FSHR receptor and carrying out gray scale analysis. Results are expressed as standard deviation ± sem. P < 0.01.
FIG. 4 is a graph of sulforaphane promoting development of mouse ovary and increasing weight of ovary in example 4 of the present invention. In the figure, A: the development of ovaries is promoted after the sulforaphane with different concentrations is injected into abdominal cavities of mice (n is 7), so that the ovaries are enlarged. B: the influence and statistics of different concentrations of sulforaphane on the change of the weight of the ovary after the intraperitoneal injection (n is 7) of the mouse are changed. C: after intraperitoneal injection of mice (5 weeks old) with S6 concentration of sulforaphane according to the A, B results, mouse ovaries of the control group, sulforaphane and follitropin group were weighed and counted together, respectively (n ═ 18).
FIG. 5 is a graph showing that sulforaphane promotes the proliferation of granulosa cells in vivo in example 5 of the present invention. In the figure, A: after the mice are injected with the sulforaphen in the abdominal cavity, the microscopic confocal detection respectively detects the level of the ovarian granular cell Edu staining markers of the control group, the sulforaphen group and the follicle-stimulating hormone group and the quantitative statistics of the proportion of the marked cells. B: after injecting sulforaphen into the abdominal cavity of the mouse, detecting the change of the levels of the proliferation marker protein PCNA of the control group and the sulforaphen group by Western blot, and performing gray level analysis. The corresponding test results are expressed as mean ± sem. P <0.001, P <0.0001, ns, not significant, P > 0.05.
FIG. 6 is a graph showing that sulforaphane promotes the production of estradiol in vivo and that steroid synthase genes such as granulosa cells StAR and CYP19A1 are expressed in example 6 of the present invention. In the figure, A: radioimmunoassay was used to detect the levels of estrogen and progestin in the serum of control and sulforaphane mice. B: and (3) analyzing the expression level and the quantification of the ovarian steroid hormone synthetase protein of the control group and the sulforaphane group mice. The results of the above corresponding experiments are expressed as mean ± sem, # P <0.05, # P <0.01, # P <0.0001, ns, not significant, P > 0.05.
FIG. 7 is a graph showing that sulforaphane promotes the expression of the FSH receptor in granulosa cells in vivo in accordance with example 7 of the present invention. After the mice are injected into the abdominal cavity of sulforaphane, Western blot detects the protein level change of ovarian FSHR receptor and performs gray scale analysis. Results are expressed as standard deviation ± sem. P < 0.0001.
FIG. 8 is a graph of sulforaphane promoting ovarian follicular development and increasing follicular numbers in mice, in accordance with example 8 of the present invention. In the figure, A: and (3) detecting the ovarian morphology of the control group and the sulforaphane group after H & E staining of the mouse ovarian paraffin. B: after H & E, the number of ovarian preantral follicles (PA) and antral follicles (a) in mice was counted (n ═ 7). Results are expressed as standard deviation ± sem. P < 0.001.
FIG. 9 is a graph of increasing ovulation in mice promoted by sulforaphane according to example 9 of the present invention. In the figure, A: and counting the ovulation number of the mice in the control group and the sulforaphane group (n is 10). Results are expressed as mean ± sem. P < 0.001. B: the ovulation rate of the control group and the sulforaphane group was counted (n ═ 17).
FIG. 10 is a graphical representation of the overall effect of sulforaphane of the present invention in enhancing reproductive performance in mammals.
Detailed Description
The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention. Unless otherwise indicated, the examples were run under conventional experimental conditions, or as recommended by the manufacturer's instructions. The present invention will be described in further detail with reference to the following examples and accompanying drawings.
The important findings of the applicant group are that the sulforaphane obviously promotes the proliferation of follicular granular cells of pigs and mice and the synthesis of steroid hormones, and the sulforaphane promotes the ovarian weight gain, the follicular development and the ovulation of the mice. The weight of the ovary and the number of the antral follicles of the mouse are increased remarkably after 48 hours of in vivo administration of the sulforaphane, and particularly, the sulforaphane can be used for replacing FSH in the mouse superovulation program to induce the ovulation of the mouse. Meanwhile, the applicant also finds that the litter size of the daily ration of the weaned sows fed with the added sulforaphen for 3 days is obviously increased. Based on the above findings, applicants have invented techniques for using sulforaphane to improve reproductive performance in mammals. The technology for improving the reproductive performance of mammals by applying the sulforaphane provides a new application of the sulforaphane, greatly improves the application value of the sulforaphane, enlarges the application range of the sulforaphane, expands a new field of applying the sulforaphane, and has wide application prospect and commercial value.
Sulforaphane, used in the following examples, was purchased from Sigma (S4441) in vitro and from aladdin (S111997) in vivo.
Example 1 sulforaphane promotes the proliferation and viability of granulosa cells in vitro, inhibits apoptosis of granulosa cells
The growth and development of follicles in the ovary are the physiological basis for oestrus and ovulation in female mammals, and granulosa cells play a very crucial role in the growth and development of follicles. The change of the particle cell activity is detected after adding different concentrations of sulforaphane (0 mu M, 1 mu M, 5 mu M, 10 mu M and 0 mu M, 1 mu M, 5 mu M, 10 mu M, 50 mu M) respectively to treat for 24h by using an in vitro culture model of the particle cells of the pigs and the mice. In mice, CCK-8 detection results show that the activity level of granular cells can be remarkably improved by low-concentration sulforaphane (1 mu M), and the activity of the granular cells can be inhibited by high-concentration sulforaphane (5 mu M, 10 mu M and 50 mu M); in pigs, low concentrations of sulforaphane (1 μ M, 5 μ M) also significantly increased the level of granulosa cell viability (fig. 1. a). Therefore, we selected low-concentration sulforaphane 5. mu.M and 1. mu.M as optimum treatment concentrations for swine and mice, respectively, to perform the following experiments. Western blot detects the expression level of cell proliferation marker protein PCNA, and finds that the expression level of the PCNA of the granulosa cells in the SFN treatment group is obviously increased (figure 1. C); the proliferation level of the granular cells is detected by using an EdU proliferation detection kit, and the proliferation level of the granular cells in the SFN treatment group is found to be remarkably increased (figure 1.B), so that the result shows that the SFN can remarkably promote the proliferation activity of the granular cells. Most follicles become locked during development and eventually involution disappears. Apoptosis of granulosa cells has been found to be the major cause of follicular atresia. Therefore, the reduction of the apoptosis level of granulosa cells has important significance on the development of follicles. We also examined the level of apoptosis in SFN-treated granulosa cells and found that the level of apoptosis marker protein clear-caspase 3 was significantly down-regulated, indicating that sulforaphane was able to inhibit apoptosis of granulosa cells (fig. 1.D) (. P <0.05,. P <0.01,. P <0.001,. P <0.0001, ns, not significant, P > 0.05).
Example 2 sulforaphane promotes the production of estradiol and the expression of steroid synthase genes such as granulosa cells StAR and CYP19A1 in vitro
Steroid hormones play a crucial role in the proliferative and differentiative properties of granulosa cells, and estrogen has been reported to significantly promote granulosa cell proliferation (saskatis et al, 1996). Therefore we examined changes in the levels of estrogen and steroid hormone synthase in granulocytes after treatment with low concentrations of sulforaphane (1 μ M). We collected pellet cell culture supernatants after 12h SFN treatment and examined estrogen levels by ELISA, and the cells found that the estrogen levels in SFN group were significantly elevated (fig. 2. a). The transcription and protein level of steroid hormone synthetase were measured by QRT-PCR and Western blot techniques, and StAR was found to be very significantly up-regulated on the mean level of mRNA and protein, the transcription levels of CYP11A1 and HSD3B genes were increased, and the expression levels of aromatase-encoding genes CYP17A1 and CYP19A1 proteins were significantly increased (FIG. 2.B/C) (. P <0.05,. P <0.01,. P <0.001,. P <0.0001, ns, not nififican, P > 0.05). The results show that low-concentration sulforaphane can promote the change of steroid hormone synthetase such as StAR, CYP19A1 and the like, and further promote the production of estrogen.
Example 3 sulforaphane promotes in vitro granulosa cell FSH receptor expression
The growth and development of the follicle and the proliferation and differentiation of the granulosa cells are simultaneously controlled by gonadotropin secreted by the pituitary and sex steroid hormone secreted by the ovary, the Follicle Stimulating Hormone (FSH) secreted by the pituitary has obvious promotion effect on the proliferation of the granulosa cells, and can promote the granulosa cells to generate FSHR and enhance the response capability to FSH, thereby continuously promoting the development of the follicle. In order to detect whether SFN can promote expression of FSH receptor, increase the response capacity of granulosa cells to FSH, and further promote granulosa cell proliferation, we also used Western blot technique to detect expression of FSH hormone receptor FSHR of granulosa cells after treating granulosa cells with low-concentration sulforaphane (1 μ M) for 12h, and found that FSHR of SFN-treated group was significantly up-regulated (fig. 3) (. p < 0.01). The results indicate that SFN may enhance the responsiveness of granulosa cells to FSH by up-regulating FSHR expression levels, promoting granulosa cell proliferation.
Example 4 sulforaphane promotes ovarian development and increases ovarian weight in mice
In vitro discovery that SFN can remarkably promote the proliferation and differentiation characteristics of granular cells, in order to study the application effect of SFN in vivo, 5-week-old mice are divided into 7 groups of control (0), S1(0.05mg/kg), S2(0.1mg/kg), S3(0.25mg/kg), S4(0.5mg/kg), S5(1mg/kg) and S6(1.25mg/kg) according to the concentration of SFN, and each group comprises 7 mice. Performing intraperitoneal injection of SFN at 8 am and 8 pm every day for two days, killing the mouse by breaking the neck after 12h of the last injection, collecting serum and ovarian tissues, photographing and weighing the ovary at one side, fixing 4% paraformaldehyde, and then slicing paraffin, wherein the ovary at the other side is used for extracting protein. As a result, the long diameter of the ovary of the group S4-S6 is obviously larger than that of the control group (figure 4.A), the weight of the ovary is obviously higher than that of the control group (figure 4.B), and the S6 action concentration is most obvious, so that the concentration of the S6 is selected in subsequent in vivo experiments. FSH is considered to be the most effective promoter for the proliferation of follicular granulosa cells. In order to compare the effect of SFN and FSH on ovarian development, mice of 5 weeks of age were divided into a control group, an SFN group and an FSH group, FSH injection was performed at the currently common dose and method (10IU-5IU-2IU-1IU), 9 mice per group were intraperitoneally injected at 8 am and 8 am every day for two days, and the mice were sacrificed by neck-breaking 12h after the last injection, and ovarian tissues were collected. As a result, both SFN and FSH were found to significantly increase ovarian weight (fig. 4.C (. x.p <0.0001), while the ovarian weight was not significantly different between SFN group and FSH group (NS, not significant, P > 0.05).
Example 5 sulforaphane promotes the proliferation of granulosa cells in vivo
To further investigate the mechanism by which SFN significantly promotes ovarian weight gain, we examined whether SFN increased ovarian weight by affecting granulosa cell proliferation by measuring proliferation levels of follicular granulosa cells in mice by in vivo injection of EdU. We used 5 week old mice divided into control, SFN and FSH groups, with 5 mice per group. Injecting SFN and FSH into the abdominal cavity at 8 am and 8 am every day for two days, injecting with EdU (5 mug/g) together at the last time of injection, killing the neck of the mouse after 12h, fixing paraformaldehyde, making paraffin sections, and detecting the change level of the EdU by using an immunofluorescence technique. As a result, the positive ratio of EdU in the cells with lumenal follicular granulosa of the SFN group and the FSH group was found to be significantly higher than that of the control group (×) P <0.0001, while there was no significant difference between the SFN group and the FSH group (fig. 5.a) (NS, not significant, P > 0.05). To further demonstrate the proliferation effect of SFN on follicular granulosa cells in mice, we used Western blot technique to detect the level of change in PCNA, a cell proliferation marker protein, and found that the PCNA level in the SFN group was significantly higher than that in the control group (fig. 5.B) (. x.p < 0.001). Experimental results prove that the sulforaphane can promote the proliferation of granular cells in vivo so as to increase the weight of the ovary.
Example 6 Desulfopristin promotes in vivo estradiol production and steroid synthase gene expression such as granulosa cell StAR and CYP19A1
To further investigate the effect of in vivo SFN injection on granulosa cell differentiation characteristics, we examined the levels of estrogen and progestin in serum of control and SFN groups using radioimmunoassay and found that the levels of estrogen and progestin were significantly increased in SFN group mice (fig. 6. a). Meanwhile, the expression level of the ovarian tissue protein steroid hormone was measured by Western blot technique, and as a result, it was found that StAR, CYP17a1 and CYP19a1 were all significantly increased in steroid hormone synthase (fig. 6.B) (. P <0.05,. P <0.01,. P <0.0001, ns, not significan, P > 0.05). The experimental results prove that the sulforaphane also promotes the expression of estrogen, progestogen and steroid hormone synthetase in vivo.
Example 7 sulforaphane promotes in vivo expression of granulosa cell FSH receptor
We have demonstrated in vitro that sulforaphane is able to up-regulate FSHR expression. To further confirm the effect of SFN on FSHR expression in vivo, we examined the expression level of FSHR protein in ovarian tissue of mice in the SFN group, and found that SFN group significantly promoted FSHR expression compared to control group (fig. 7) (. P < 0.001). Experiments prove that the SFN can also promote the expression of FSHR in vivo and enhance the response capability of mouse ovary to gonadotropin, thereby promoting the development of mouse ovary.
Example 8 sulforaphane promotes ovarian follicular development in mice and increases follicular numbers
To further investigate the effect of sulforaphane on mouse ovarian development, we used HE staining, observed morphological changes in mouse ovaries and statistically analyzed the number of follicles at each level. By paraffin embedding the control group and the SFN group, 7 ovaries are arranged in each group, then, when the embedded ovarian tissue section is cut to be close to the maximum cross section, one ovary is taken at intervals of 10 cuts, 10 ovaries are taken for HE staining, the shape of the ovary is observed, and the number of follicles at each stage is counted. As a result, SFN group ovarian tissue was found to increase significantly, and both pre-antral (PA) and antral (a) follicles were increased significantly (fig. 8.a) (. P < 0.001). Experimental results prove that the number of follicles can be obviously increased by intraperitoneal injection of the sulforaphane.
Example 9 sulforaphane promotes ovarian follicular development in mice and increases ovulation number
We have demonstrated that sulforaphane can promote the development of mouse ovary, and to further study the effect of sulforaphane on mouse ovulation, we divided 5-week-old mice into a control group and an SFN group of 17 mice each. Injecting physiological saline and SFN into the abdominal cavity at 8 am and 8 am every day for two days, removing the neck after 12h, killing the mouse, collecting the oviduct, wherein 10 oocytes in the oviduct of the mouse are detected and counted, and the other 7 oocytes are counted to determine whether to ovulate. As a result, the number of ovulations was significantly higher in the SFN group than in the control group (fig. 9.a) (. x.p < 0.001); more interestingly, all mice in the SFN group ovulated, and the ovulation rate reached 100% (17/17), the control group had only 47.06% (8/17) of ovulation rate (fig. 9. a); the experimental result proves that the sulforaphane can promote the ovulation of the ovarian follicles of the mice and increase the ovulation number.
Example 10 adding sulforaphane to daily ration of weaned sows significantly improves farrowing performance of sows
Broccoli extract containing sulforaphane (batch No. 200319) was purchased from Angelica shikei Biotech Co., Ltd, and added to feed for weaned sows in an amount such that the daily intake of sulforaphane per sow was 100 mg. Feeding the sows after birth and birth for 3 days, continuously feeding the sows for 3 days, performing oestrus identification and mating treatment according to a conventional method after 3 days, and counting the characters such as litter size and the like after delivery of the sows. The research shows that (table 1), the average litter size of the grown multiparous sow (34 litters) fed with the sulforaphane-containing feed is 15.3, which is obviously higher than the level of 12.6 in a control group (33 litters); the number of alive animals in the test group reached 14.7, while the number in the control group reached 11.8, and the difference between them was equally significant (significant difference between different letters).
TABLE 1 influence of daily ration of weaned sows on farrowing performance by adding sulforaphane
Note: a. b different letters represent significant differences.
Claims (6)
1. Application of sulforaphane and its derivatives in preparing product for improving mammal reproductive performance is provided.
2. Application of sulforaphane and derivatives thereof in preparing mature products for promoting follicular granulosa cell proliferation.
3. Application of sulforaphane and derivatives thereof in preparing products for promoting ovarian follicle development.
4. Application of sulforaphane and derivatives thereof in preparing products for promoting estrus and ovulation.
5. The use according to claim 1, characterized in that the effective concentration of sulforaphane is: not higher than 10 μ M in vitro and not higher than 5mg/kg in vivo.
6. The use according to claim 5, characterized in that the effective concentration of sulforaphane is: 1-10 μ M in vitro and 0.1-5 mg/kg in vivo.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112402590A (en) * | 2020-12-11 | 2021-02-26 | 青岛德瑞骏发生物科技股份有限公司 | An equine reproduction promoter |
| CN113025700A (en) * | 2021-03-05 | 2021-06-25 | 中国农业科学院北京畜牧兽医研究所 | Use of STAR and regulatory genes thereof |
| CN113249304A (en) * | 2021-06-04 | 2021-08-13 | 中国农业科学院北京畜牧兽医研究所 | Application of sulforaphane in preparation of bovine oocyte in-vitro maturation liquid |
| CN116144708A (en) * | 2022-09-29 | 2023-05-23 | 西南大学 | All-male sterile nile tilapia strain and construction method thereof |
-
2020
- 2020-07-20 CN CN202010701931.XA patent/CN111686101A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| 刘风藏: "莱菔硫烷对大鼠肾缺血再灌注诱发肠损伤的影响", 《中国优秀硕士学位论文全文数据库（电子期刊）》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112402590A (en) * | 2020-12-11 | 2021-02-26 | 青岛德瑞骏发生物科技股份有限公司 | An equine reproduction promoter |
| CN112402590B (en) * | 2020-12-11 | 2022-06-14 | 青岛德瑞骏发生物科技股份有限公司 | An equine animal breeding promoter |
| CN113025700A (en) * | 2021-03-05 | 2021-06-25 | 中国农业科学院北京畜牧兽医研究所 | Use of STAR and regulatory genes thereof |
| CN113249304A (en) * | 2021-06-04 | 2021-08-13 | 中国农业科学院北京畜牧兽医研究所 | Application of sulforaphane in preparation of bovine oocyte in-vitro maturation liquid |
| CN116144708A (en) * | 2022-09-29 | 2023-05-23 | 西南大学 | All-male sterile nile tilapia strain and construction method thereof |
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