Food or feed containing ergothioneine

Abstract

To provide a highly safe food or feed that can increase female fertility in human or non-human mammal, or that can decrease female estrus recursion days.SOLUTION: Provided is a method for improving fertility of mammalian female, which is a method for ingesting ergothioneine-containing food or feed into a subject mammalian female in order to increase fertility of mammalian female, or to decrease estrus recursion days, and in which a food or feed whose intake of ergothionein by mammalian female is 0.18 mg / kg body weight / day or more is ingested into non-human mammalian female.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a food or feed containing ergothioneine for improving fertility in female mammals, and a method for improving fertility in female mammals by ingesting ergothioneine. [Background technology]

[0002] In recent years, the trend of later marriage in Japan has led to an increase in the number of women using assisted reproductive technology. This is because the average age of women hoping to become pregnant is rising, while women's fertility declines with age, leading to an increase in cases where medical intervention is required to become pregnant. Treatments to increase women's fertility include the use of ovulation-inducing drugs and hormones, but these treatments are known to have a number of side effects.

[0003] In order to improve productivity in non-human mammals, particularly in cattle, pigs, sheep, and other animals used for meat, it is desirable to increase the average number of offspring in multiparous animals and to increase the birth frequency in singleparous animals. It is also desirable to increase the number of pregnancies per unit time in both multiparous and singleparous animals.

[0004] Ergothioneine is a type of amino acid contained in mushrooms such as Tamogitake mushroom and used as an antioxidant in cosmetics. Patent Document 1 reports that the ergothioneine content in Tamogitake mushroom is 15.8±0.06 mg per 1 g dry weight. Non-Patent Document 1 shows that ergothioneine, when ingested by humans and animals as food, takes a long time to metabolize, so it is likely to accumulate in many tissues and body fluids of humans and animals. It has been confirmed in vitro that ergothioneine has antioxidant and cytoprotective effects, and it has been suggested that it is involved in the repair of tissue damage in the human and animal bodies. In humans, ergothioneine is expected to be a highly safe food-derived component that has therapeutic effects on neurodegenerative diseases, eye diseases, cardiovascular diseases, kidney diseases, diabetes, etc. due to its antioxidant and cytoprotective effects. However, the fertility-improving effect of ergothioneine in humans or mammals other than humans has not been reported so far. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent Publication 2012-105618 [Non-patent literature]

[0006] [Non-Patent Document 1] B. Halliwell et al., FEBS letters, vol.592, pp. 3357-3366 (2018) Summary of the Invention [Problem to be solved by the invention]

[0007] An object of the present invention is to provide a highly safe food or feed that is capable of improving female fertility or reducing the number of days for estrus to return in humans or non-human mammals. [Means for solving the problem]

[0008] As a result of intensive research, the present inventors have found that fertility of mammals is increased and / or the number of days for estrus to return is reduced by ingesting ergothioneine, and have completed the present invention. That is, the present invention provides the following. (1) Food or feed for improving fertility or reducing the number of days to return to estrus in female mammals, containing ergothioneine. (2) The food or feed of (1), in which the ergothioneine intake of a female of the mammal is 0.18 mg / kg body weight / day or more. (3) A method for improving fertility in female mammals, comprising administering ergothioneine to female non-human mammals. (4) The method according to (3), wherein the intake of ergothioneine in the female non-human mammal is 0.18 mg / kg body weight / day or more. (5) A method for decreasing the number of days to return to estrus in a female non-human mammal by administering ergothioneine to the female mammal. (6) The method according to (5), wherein the intake of ergothioneine in the female non-human mammal is 0.18 mg / kg body weight / day or more. Effect of the Invention

[0009] According to the present invention, it is possible to provide a highly safe food or feed that can improve female fertility or reduce the number of days for estrus to return in humans or non-human mammals. [Brief description of the drawings]

[0010] [Figure 1] FIG. 1 is a schematic diagram showing the procedure for producing mice by repeated superovulation stimulation in Example 1. [Diagram 2] 1 is a line graph showing the estrous cycle patterns of a 3-month-old control mouse (A) and a mouse that had been subjected to six rounds of superovulation stimulation (B). [Diagram 3]1 is a bar graph showing the length of one estrous cycle in control mice and mice after superovulation stimulation. An "*" in the figure indicates a p-value of less than 0.05 in the Student's t-test. [Figure 4] 1 is a bar graph showing the number of ovulated eggs in 3-month-old mice and mice that underwent repeated superovulation stimulation. In the figure, "**" indicates that the p-value in the Student's t-test was less than 0.01. [Diagram 5] FIG. 1 is a line graph showing the estrous cycle patterns of mice without ergothioneine administration (A) and mice with ergothioneine administration (B). [Figure 6] 1 is a bar graph showing the length of one estrous cycle in mice without and with ergothioneine administration. An "*" in the figure indicates that the p-value in the Student's t-test was less than 0.05. [Figure 7] 1 is a bar graph showing the number of ovulated eggs in control mice and mice that were repeatedly superovulated without and with ergothioneine administration. In the figure, "*" and "**" indicate that the p-value in the Student's t-test was less than 0.05 and 0.01, respectively. [Figure 8] FIG. 1 is a schematic diagram showing the procedure for administering ergothioneine in drinking water to mice in Example 4. [Figure 9] 1 is a bar graph showing the number of ovulated eggs in control mice and mice administered ergothioneine in each test group. In the figure, "*" indicates that the p value in the Student's t-test was less than 0.05. [Figure 10] 1 is a bar graph showing the number of eggs ovulated in control mice and mice treated with various doses of ergothioneine. An "*" in the figure indicates a p-value of less than 0.05 in the Student's t-test. [Figure 11] 1 is a bar graph showing the average number of pups per litter in control and ergothioneine-treated mice. An "*" in the figure indicates a p-value of less than 0.05 in the Student's t-test. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] <1. Food or feed> The food or feed of the present invention contains ergothioneine and is characterized in that it improves fertility or reduces the number of days for estrus to return in female mammals. In the present invention, "food" refers to a substance or composition in a form suitable for human ingestion. Also, in the present invention, "feed" refers to a substance or composition in a form suitable for animals other than humans to ingest.

[0012] In the present invention, "ergothioneine" refers to a compound represented by the following formula I and its derivatives. All stereoisomers having the structural formula of the following formula I are included. The derivatives referred to here include metal salts, hydrates, etc., but are not particularly limited as long as they have the skeleton of the following formula I.

[0013] [ka]

[0014] Ergothioneine is contained in mushrooms such as Tamogitake, Oyster Mushroom, King Oyster Mushroom, Sparassis crispa, Enokitake, and Shiitake mushrooms, and is known to be contained in Tamogitake in particular. Ergothioneine may be purified from raw materials such as mushrooms containing ergothioneine and added to the food or feed of the present invention. As a method for purifying ergothioneine, for example, the method shown in Patent Document 1 can be used. Alternatively, ergothioneine may be contained in the food or feed of the present invention as unrefined finely ground raw materials such as mushrooms containing ergothioneine, dried powder, concentrated extract, etc. In the present invention, ergothioneine is preferably contained in the food or feed as a dried powder or concentrated extract of mushrooms, particularly as a dried powder or concentrated extract of Tamogitake.

[0015] In the present invention, "mammal" refers to animals belonging to the phylum Chordata, subphylum Vertebrate, class Mammalia, including humans and non-humans, and includes, for example, primates including humans and chimpanzees, pet animals such as dogs and cats, livestock animals such as cows, pigs, horses, sheep, goats, rodents such as mice and rats, mammals kept in zoos, etc. The subjects to be ingested with the food or feed of the present invention are preferably humans or livestock animals such as cows, pigs, sheep, etc.

[0016] In the present invention, "fertility" means the ease with which a female mammalian animal can become pregnant. In the present invention, improvement of fertility is determined by the stabilization or shortening of the estrous cycle, and in the case of multiparous animals, an increase in the number of offspring per birth. In human adult females, one of the causes of infertility is a disruption or prolongation of the menstrual cycle. One of the objects of the present invention is to stabilize this, thereby improving fertility.

[0017] In the present invention, the "number of days to estrus recurrence" refers to the number of days from when a female mammalian animal weans a previously born child until the animal goes into estrus again. By decreasing the number of days to estrus recurrence, it is possible to increase the number of births per unit period (e.g., one year), and as a result, to increase the number of offspring per unit period.

[0018] In a study using mice in the examples of this specification, the estrous cycle of mice was lengthened by repeated superovulation stimulation, but in mice administered ergothioneine simultaneously with the superovulation stimulation, the estrous cycle was shortened to the same length as that of normal mice. Furthermore, the number of ovulations in the oviducts of mice administered ergothioneine was greater than that of normal mice. Furthermore, in a study using pigs, a decrease in the number of days for estrus recurrence and an increase in the number of offspring were observed in pigs that ingested ergothioneine. Thus, it was revealed that ergothioneine has the effect of improving the fertility of female mammals and the effect of reducing the number of days for estrus recurrence. The present invention is to include ergothioneine having the above-mentioned effect in food or feed, thereby improving the fertility and / or reducing the number of days for estrus recurrence in female mammals that ingest it.

[0019] The form of the food or feed of the present invention is not particularly limited as long as it can be easily ingested by the target mammalian animal, and may be, for example, a liquid (beverage), powder, granules, tablet, capsule, etc. Furthermore, the food or feed of the present invention may contain a carrier as necessary. Examples of the carrier include excipients, binders, disintegrants, fillers, emulsifiers, flow additive regulators, lubricants, etc.

[0020] Examples of excipients include sugars such as monosaccharides, disaccharides, cyclodextrins, and polysaccharides (more specifically, including, but not limited to, glucose, sucrose, lactose, raffinose, mannitol, sorbitol, inositol, dextrin, maltodextrin, starch, and cellulose), metal salts (e.g., sodium chloride, sodium or calcium phosphate, calcium sulfate, magnesium sulfate, calcium carbonate), citric acid, tartaric acid, glycine, low, medium, and high molecular weight polyethylene glycols (PEGs), pluronics, kaolin, silicic acid, or combinations thereof.

[0021] Examples of binders include starch paste using corn, wheat, rice, or potato starch, simple syrup, glucose solution, gelatin, tragacanth, methylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, shellac, and / or polyvinylpyrrolidone.

[0022] Examples of disintegrants include the above-mentioned starches, lactose, carboxymethyl starch, cross-linked polyvinylpyrrolidone, agar, laminaran powder, sodium hydrogen carbonate, calcium carbonate, alginic acid or sodium alginate, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, stearic acid monoglyceride, or salts thereof.

[0023] Examples of the filler include the above-mentioned sugars and / or calcium phosphate (eg, tricalcium phosphate or calcium hydrogen phosphate).

[0024] Examples of emulsifiers include sorbitan fatty acid esters, glycerin fatty acid esters, sucrose fatty acid esters, and propylene glycol fatty acid esters.

[0025] Examples of flow regulators and lubricants include silicates, talc, stearates or polyethylene glycol.

[0026] Such carriers are used to maintain the shape of the product and the effect of ergothioneine, and may be used appropriately as necessary. In addition to the above-mentioned additives, the product may also contain flavorings, solubilizers, suspending agents, diluents, surfactants, stabilizers, absorption promoters, bulking agents, wetting agents, humectants, adsorbents, disintegration inhibitors, coating agents, colorants, preservatives, antioxidants, fragrances, flavorings, sweeteners, buffers, etc., if necessary.

[0027] The food or feed of the present invention may be ingested as it is, or may be mixed with other foods or feeds or added to drinking water. In particular, when it is ingested by mammals other than humans, it may be ingested by mixing with other feeds or dissolving in drinking water in order to ensure that the required amount is ingested.

[0028] In the food or feed of the present invention, the content of ergothioneine is preferably adjusted so that the intake amount of a mammalian animal ingesting the food or feed is 0.18 mg / kg body weight / day or more, particularly 0.36 mg / kg body weight / day or more. The upper limit of the intake amount is not particularly limited, but the amount that can be ingested as food or feed can be, for example, 10.0 mg / kg body weight / day or less, particularly 5.0 mg / kg body weight / day or less, and further 3.2 mg / kg body weight / day or less. Note that 3.2 mg / kg body weight corresponds to the amount of ergothioneine that a human adult female (assumed to weigh 50 kg) can ingest when eating 100 g (raw weight) of Pleurotus cornucopiae.

[0029] The food or feed of the present invention preferably contains 1 / 5 to 3 times, and particularly 1 / 3 to 1 times, the daily intake amount of ergothioneine per serving, i.e., the intake frequency is preferably once every 3 days to 5 times a day, and particularly once to 3 times a day.

[0030] The timing and period for which the food or feed of the present invention is ingested by a mammalian animal is not particularly limited, and may be ingested daily, for example, or only during the period from a few days before ovulation until mating, for example.

[0031] <2. Method for improving fertility in female mammals> The present invention includes a method for improving fertility in a female mammalian animal, comprising having a female non-human mammalian animal ingest ergothioneine. In the present invention, the means for having a mammalian animal ingest ergothioneine is preferably having the mammalian animal ingest the feed of the present invention.

[0032] In the present invention, "non-human mammals" refers to all animals other than humans that belong to the phylum Chordata, subphylum Vertebrate, class Mammalia, including primates including chimpanzees, pet animals such as dogs and cats, livestock animals such as cows, pigs, horses, sheep, goats, rodents such as mice and rats, mammals kept in zoos, etc. The subjects to which the method of the present invention is applied are preferably livestock animals such as cows, pigs, sheep, etc.

[0033] In the present invention, the amount of ergothioneine ingested by a mammal is preferably 0.18 mg / kg body weight / day or more, particularly 0.36 mg / kg body weight / day or more. The upper limit of the intake amount is not particularly limited, but can be, for example, 10.0 mg / kg body weight / day or less, particularly 5.0 mg / kg body weight / day or less, and further 3.2 mg / kg body weight / day or less.

[0034] In the method of improving the fertility of female mammals of the present invention, the definitions of "ergothioneine" and "fertility", the preferred form of feed containing ergothioneine, the method and frequency of ingestion, etc. are all as described in the section <1. Food or feed>.

[0035] <3. Methods for reducing the number of days for which estrus returns in female mammals> The present invention includes a method for reducing the number of days until estrus recurs in a female mammalian animal, comprising administering ergothioneine to a non-human female mammalian animal. In the present invention, the means for administering ergothioneine to a mammalian animal is preferably the administration of the feed of the present invention.

[0036] In the method of the present invention for reducing the number of days until estrus recurs in a female mammal, the target mammal, the amount of ergothioneine to be ingested by the mammal, the definitions of "ergothioneine" and "number of days until estrus recurs," the preferred form of the feed containing ergothioneine, the method and frequency of ingestion, etc. are all as described in the sections <1. Food or feed> and <2. Method for improving fertility of female mammal>.

[0037] <4. Methods for improving fertility in human females> The present invention also includes a method for improving fertility in a human female. The method for improving fertility in a human female of the present invention is characterized in that the human female ingests ergothioneine. In the present invention, the means for ingesting ergothioneine in a human female is preferably by ingesting the food product.

[0038] In the method of improving fertility in human females of the present invention, the definitions of "ergothioneine" and "fertility", the preferred form, intake amount, intake method and intake frequency of foods containing ergothioneine, etc. are all as described in the sections <1. Food or feed> and <2. Method of improving fertility in female mammals>. EXAMPLES

[0039] <Example 1: Generation of mice by repeated superovulation stimulation> Three-week-old immature C57BL6 mice were administered equine chorionic gonadotropin (eCG) (a follicle-stimulating hormone (FSH) preparation) and human chorionic gonadotropin (hCG) (a luteinizing hormone (LH) preparation) to stimulate superovulation, and mice were generated that underwent repeated superovulation stimulation. Specifically, 4 I.U of eCG was administered by subcutaneous injection, followed by 5 I.U of hCG two days later. This process was repeated six times every 10 days (Figure 1). After each administration, the mice were subjected to vaginal cavity examination, and their estrous cycle was observed. In addition, vaginal cavity examination was also performed on 3-month-old and 6-month-old mice that had not been administered hormone drugs as control mice. The number of control mice and superovulation-stimulated mice tested was three each, and the mean ± standard error of each measurement was calculated.

[0040] Figure 2 shows the estrous cycle patterns of 3-month-old control mice (Figure 2A) and mice that underwent six superovulatory stimulations (Figure 2B). Figure 3 shows the length of one estrous cycle in each control mouse and each superovulatory stimulation. An "*" in the figure indicates that the p-value in the Student's t-test was less than 0.05. The estrous cycle in the control mice was 4.7 ± 0.9 days, whereas in the mice that underwent six superovulatory stimulations, microestrus was observed continuously and the estrous cycle was prolonged to 8.1 ± 1.1 days.

[0041] Mice that had been subjected to six rounds of superovulation stimulation were further subjected to one round of superovulation stimulation (administration of eCG and hCG). 16 hours after administration of hCG, the oviducts were collected and the number of ovulated eggs was measured. The number of ovulated eggs was also measured in the same manner for 3-month-old mature female control mice. Three control mice and three superovulation-stimulated mice were tested, and the average value ± standard error of each measurement was calculated.

[0042] Figure 4 shows the number of eggs ovulated in 3-month-old mice and mice that underwent repeated superovulation stimulation. In the figure, "**" indicates that the p-value was less than 0.01 in the Student's t-test. In the 3-month-old mice, 16.6±2.3 eggs were ovulated, but in the mice that underwent repeated superovulation, only 5.3±0.3 eggs were ovulated, a significant decrease. Therefore, it was revealed that repeated superovulation stimulation reduces the fertility of female mice.

[0043] <Example 2: Examination of the effect of ergothioneine on the lengthening of the estrous cycle> Three-week-old immature C57BL6 mice were continuously administered 1.8 mg / kg body weight / day of ergothioneine in drinking water, and superovulation stimulation was performed six times every 10 days. The mice were subjected to vaginal cavity examination, and their estrous cycle was observed. As control mice, mice treated under the same conditions except for omitting ergothioneine administration were also observed for their estrous cycle. Three mice were tested each with and without ergothioneine administration, and the mean ± standard error of each measured value was calculated.

[0044] Figure 5 shows the estrous cycle patterns of mice without ergothioneine administration (Figure 5A) and with ergothioneine administration (Figure 5B). Figure 6 shows the length of one estrous cycle of mice without and with ergothioneine administration. An "*" in the figure indicates that the p-value in the Student's t-test was less than 0.05. In mice that underwent six repeated superovulation stimulations, the microestrus period continued and the estrous cycle was prolonged to 11 ± 0.7 days. On the other hand, when superovulation stimulation was repeated six times while ergothioneine was administered in drinking water, no prolongation of the estrous cycle was observed (4.9 ± 0.2 days).

[0045] <Example 3: Examination of the effect of ergothioneine on decreased hormone sensitivity> Mice were continuously administered 1.8 mg / kg body weight / day of ergothioneine in drinking water and were subjected to six superovulation stimulations every 10 days, and then further superovulation stimulations (eCG and hCG administration) were performed once. Then, 16 hours after hCG administration, the oviducts were collected and the number of ovulated eggs was measured. For comparison, the number of ovulated eggs was measured for mice treated under the same conditions except that ergothioneine administration was omitted. The number of ovulated eggs was also measured for 3-month-old mature female mice as control mice. The number of control mice and mice without and with ergothioneine administration was 5 each, and the mean ± standard error of each measurement value was calculated.

[0046] FIG. 7 shows the number of ovulated eggs in the control mice and the mice that were repeatedly stimulated by superovulation without and with ergothioneine administration. In the figure, "*" and "**" indicate that the p-values ​​in the Student's t-test were less than 0.05 and less than 0.01, respectively. In the mice that were repeatedly stimulated by superovulation six times, the number of ovulations was significantly reduced compared to the control mice (9±1.7 ovulations). On the other hand, in the mice that were repeatedly stimulated by superovulation and administered ergothioneine, the number of ovulations increased dramatically. The number of ovulations in the control mice, mice without ergothioneine administration, and mice with ergothioneine administration was 23±1.2, 9±1.7, and 30±2.6, respectively. Therefore, it was revealed that long-term administration of ergothioneine in drinking water has the effect of preventing the decrease in fertility caused by repeated superovulation stimulation.

[0047] <Example 4: Examination of the timing of administration of ergothioneine> To examine the effects of ergothioneine on young mice, 1.8 mg / kg body weight / day of ergothioneine was administered in drinking water, starting at the same time as eCG administration (Test Group 1) and two days before (Test Group 2). Figure 8 shows an outline of ergothioneine administration in drinking water for Test Groups 1 and 2. 48 hours (two days) after eCG administration, hCG was administered, and 16 hours later, the oviducts were collected and the number of ovulated eggs was measured. The number of ovulated eggs was also measured for control mice of the same age that were not administered ergothioneine. The number of control mice and mice in Test Groups 1 and 2 was 5 each, and the mean ± standard error of each measured value was calculated.

[0048] Figure 9 shows the number of eggs ovulated in the control mice and the mice in test groups 1 and 2. The "*" in the figure indicates that the p-value in the Student's t-test was less than 0.05. It was revealed that the number of ovulations was significantly increased by administering ergothioneine in drinking water starting from two days before eCG administration.

[0049] <Example 5: Examination of optimal concentration of ergothioneine> To determine the optimal concentration of ergothioneine, 0.09, 0.18, 0.36, 0.9, and 1.8 mg / kg body weight / day of ergothioneine were administered in drinking water starting 2 days before eCG administration, and hCG was administered 48 hours later. 16 hours after hCG administration, oviducts were collected from each mouse, and the number of eggs ovulated was measured. In addition, the number of eggs ovulated was measured for control mice of the same age that were not administered ergothioneine. The number of control mice and mice administered ergothioneine at each dose was three for each test, and the mean ± standard error of each measurement value was calculated.

[0050] Figure 10 shows the number of eggs ovulated in control mice and mice administered ergothioneine at various doses. In the figure, "*" indicates that the p-value in the Student's t-test was less than 0.05. The number of ovulations increased depending on the amount of ergothioneine administered, with the highest number of ovulations observed at 1.8 mg / kg body weight / day.

[0051] <Example 6: Examination of the effect of ergothioneine on mouse litter size> To clarify the effect of ergothioneine on the number of offspring, 3-month-old female mice were bred with males for 3 months under conditions where they were administered 1.8 mg / kg body weight / day of ergothioneine in their drinking water. The number of offspring per birth was measured during that period. As control mice of the same age were treated in the same way except that they were not administered ergothioneine, and the number of offspring per birth was measured. Four control mice and four mice administered ergothioneine were tested, and the mean ± standard error of each measurement was calculated.

[0052] Figure 11 shows the average number of offspring per birth for control mice and mice administered ergothioneine. In the figure, "*" indicates that the p-value in Student's t-test was less than 0.05. The number of offspring born was significantly increased by administering ergothioneine to drinking water. In other words, it was revealed that ergothioneine has the effect of improving fertility by increasing the number of ovulations in females.

[0053] <Example 7: Examination of the effect of ergothioneine on pig fertility and number of days to return to estrus> Thirteen multiparous sows (excluding primiparous ones) were fed Tamogitake powder so that their ergothioneine intake was 0.36 mg / kg body weight / day from weaning to mating (Test group 3). For each individual, the number of days to estrus return (number of days from weaning to estrus) and the number of offspring at the first birth after Tamogitake intake were counted. In addition, the number of days to estrus return and the number of offspring were counted for each individual in the control group that did not receive Tamogitake.

[0054] The number of pigs, number of days to estrus recurrence, and number of offspring in the test group 3 and the control group are shown in Table 1. The average value ± standard deviation for each group was calculated for the number of days to estrus recurrence and number of offspring. There were two pigs in the control group whose number of days to estrus recurrence exceeded 50 days, but these were not included in the calculation of the average number of days to estrus recurrence.

[0055] [Table 1]

[0056] As shown in Table 1, in test group 3 where pigs were fed Tamogitake mushrooms, the number of offspring born increased by an average of about one compared to the control group. In addition, a decrease in the number of days until estrus recurred was also observed. From the above results, it was found that ergothioneine also has a fertility-enhancing effect in pigs. It was also found that ergothioneine has an effect of decreasing the number of days until estrus recurs.

Claims

1. A food or feed for stabilizing or shortening the estrus cycle of a female mammal, comprising ergothioneine.

2. A feed containing ergothioneine for increasing the number of offspring per birth in female mammalian multiparous animals.

3. The food described in claim 1 or the feed described in claim 1 or 2, wherein the intake amount of ergothioneine is 0.18 mg / kg body weight / day or more.

4. A method for stabilizing or shortening the estrous cycle of a female non-human mammal, comprising administering ergothioneine to the female non-human mammal.

5. 5. The method of claim 4, wherein the non-human mammalian female has an intake of ergothioneine of 0.18 mg / kg body weight / day or more.

6. A method for increasing the number of offspring per birth in female mammalian animals that are multiparous, comprising having the female mammalian animal ingest ergothioneine.

7. The method described in claim 6, wherein the intake of ergothioneine in the female of the mammalian multiparous animal is 0.18 mg / kg body weight / day or more.

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