Applications of UDCA in the preparation of formulations that reduce the incidence of intrauterine growth retardation in pregnant sows and in feed.

Abstract

This application relates to the field of feed, specifically to the application of UDCA in the preparation of formulations that reduce the incidence of intrauterine growth retardation (IUGR) in pregnant sows. According to the technical solution of this application, by adding 0.05% ursodeoxycholic acid to the diet of sows during late gestation (85 days) to the farrowing stage, using a restricted feeding method, at a rate of 2 kg / head / day, twice daily, the incidence of IUGR in sows can be effectively reduced by up to 76.17%, while also increasing the average weaning weight of piglets at 28 days by 9.61%.

Description

Technical Field

[0001] This application relates to the field of feed, specifically to the application of UDCA in the preparation of formulations that reduce the incidence of intrauterine growth retardation in pregnant sows and its use in feed. Background Technology

[0002] Intrauterine growth restriction (IUGR) is a prominent problem in the pig industry, leading to low birth weight, high mortality during lactation, and poor growth performance throughout the life cycle. IUGR affects the gastrointestinal development of piglets and continuously damages organs such as the gastrointestinal tract, liver, and muscles, disrupting the expression of absorption and metabolism-related proteins, thereby reducing feed utilization efficiency.

[0003] Studies have shown that oxidative stress can damage the antioxidant system and cause various pregnancy complications such as preterm birth, intrauterine growth restriction (IUGR), and abortion. Furthermore, research reports that IUGR pigs exhibit increased placental reactive oxygen species, decreased antioxidant capacity, mitochondrial and placental structural damage, and exacerbated oxidative damage. Therefore, improving the oxidative stress status of pregnant sows is of great significance for reducing the incidence of IUGR and improving sow reproductive performance.

[0004] UDCA, chemically known as 3α,7β-dihydroxy-5β-cholestan-24-acid, is odorless and bitter. In medicine, it is used to increase bile acid secretion, alter bile composition, and reduce cholesterol and cholesterol esters in bile, thus facilitating the gradual dissolution of cholesterol in gallstones. Furthermore, clinical trials have demonstrated the effectiveness of UDCA in treating liver diseases. However, there are no reports on the application of UDCA in pregnant sows to promote fetal development and reduce the incidence of IUGR (intrauterine growth restriction). Summary of the Invention

[0005] This application aims to reduce the incidence of IUGR in sows by alleviating oxidative stress during late pregnancy.

[0006] The purpose of this application is to provide the use of 3a,7β-dihydroxy-5β-cholestane-24-acid in the preparation of formulations that reduce the incidence of intrauterine growth retardation in pregnant pig fetuses.

[0007] Another objective of this application is to provide feed that reduces the incidence of intrauterine growth retardation in pregnant sows.

[0008] According to the technical solution of this application, 3a,7β-dihydroxy-5β-cholestan-24-acid is used to prepare an agent that reduces the incidence of intrauterine growth retardation in pregnant pig fetuses, wherein the pregnant pigs are those from 85 days of gestation to the parturition stage.

[0009] The feed for reducing the incidence of intrauterine growth retardation in pregnant sows according to this application contains 3a,7β-dihydroxy-5β-cholestan-24-acid, wherein the pregnant sow is from day 85 of gestation to parturition.

[0010] According to the technical solution of this application, by adding 0.05% ursodeoxycholic acid to the diet of sows during the late pregnancy period (85 days) to the farrowing stage, and adopting a restricted feeding method, the feeding amount is 2 kg / head / day, and feeding is done twice a day, which can effectively reduce the incidence of IUGR pigs by up to 76.17%, and at the same time increase the average weaning weight of piglets at 28 days by 9.61%. Attached Figure Description

[0011] Figure 1-1 , Figure 1-2 , Figure 1-3 , Figure 1-4 This study compared and analyzed the blood metabolic components and blood oxidative stress indicators of sows at 70 days and 28 days of gestation. Figure 1-1 : Orthogonal partial least squares discriminant analysis (OPLS-DA) plot of blood metabolomics; Figure 1-2 Changes in the relative content of ursodeoxycholic acid (UDCA); Figure 1-3 Blood oxidative stress-related indicators; Figure 1-4 Correlation between blood bile acid components and blood oxidative stress indicators (*P<0.05; **P<0.01; ***P<0.001). Detailed Implementation

[0012] Example 1

[0013] Metabolomics analysis comparing the composition of blood metabolites in sows during late and early pregnancy revealed that ursodeoxycholic acid (UDCA) levels in the blood of sows during late pregnancy were significantly lower than those in sows during early pregnancy, by approximately 7 times. Further analysis showed a significant positive correlation between UDCA and antioxidant indicators in sow blood, indicating that increased oxidative stress in sows during late pregnancy was accompanied by a decrease in UDCA levels, suggesting that increased maternal oxidative stress during late pregnancy may be related to a reduction in UDCA.

[0014] like Figure 1-1 , Figure 1-2 , Figure 1-3 , Figure 1-4 As shown, metabolomics analysis revealed significant differences in blood metabolite composition in sows during the last 70 days of gestation compared to the first 28 days of gestation. Figure 1-1 The content of secondary bile acids (UDCA) was significantly reduced. Figure 1-2This indicates that bile acid homeostasis in sows changes during the mid-to-late stages of pregnancy. Simultaneously, oxidative stress in sows intensifies during day 70 of gestation, manifested by increased levels of malondialdehyde (MDA), an indicator of oxidative stress damage, and decreased levels of catalase (CAT), an antioxidant indicator, in the blood. Figure 1-3 Furthermore, association analysis revealed a significant negative correlation between UDCA and MDA in the blood, and a significant positive correlation between UDCA and CAT in the blood. Figure 1-4 ).

[0015] Example 2

[0016] Twenty-four healthy Landrace × Large White sows (85 days gestation) were randomly divided into two groups (n=12). The control group was fed a corn-soybean meal basal diet, while the treatment group was fed a basal diet supplemented with ursodeoxycholic acid (UDCA) (0.05%) (diet formula shown in Table 1). Restricted feeding was used, with a feed intake of 2 kg / sow / day, fed in equal amounts at 8:00 AM and 4:00 PM. The experimental period lasted from 85 days of gestation to farrowing. During this period, all sows consumed pelleted feed and had free access to water. They were managed according to routine immunization and deworming programs, and their health status was observed. Piglet growth performance was monitored from farrowing to weaning.

[0017] Adding 0.05% UDCA to the diet of sows during late gestation (85 days) significantly increased the average birth weight of piglets by 17.45%, reduced the incidence of IUGR by up to 76.17%, and reduced the stillbirth rate by 58.89% (Table 2); it also increased the average weight of weaned piglets by 9.61% (Table 3). The results indicate that UDCA supplementation during late gestation improves sow reproductive performance, particularly in reducing the incidence of IUGR in piglets.

[0018] Comparative Example 1

[0019] Sixteen healthy Landrace × Large White sows (85 days gestation) were randomly divided into two groups (n=8). The control group was fed a corn-soybean meal basal diet, while the treatment group was fed a basal diet supplemented with chenodeoxycholic acid (CDCA) (0.05%). The diet formula is shown in Table 4. A restricted feeding method was adopted, with a feeding amount of 2 kg / sow / day, fed in equal amounts at 8:00 AM and 4:00 PM. The experimental period was from 85 days of gestation to farrowing. During this period, all sows consumed pelleted feed and had free access to water. They were managed according to routine immunization and deworming programs, and their health status was observed. Piglet growth performance was monitored from farrowing to weaning.

[0020] Supplementing the diet with 0.05% CDCA during late gestation (85 days) of sows had no significant effect on the average birth weight of piglets, the incidence of IUGR, or the stillbirth rate (Table 5). These results indicate that supplementing with CDCA during late gestation has no effect on sow reproductive performance or the incidence of IUGR in piglets.

[0021] Table 1. Dietary formulation and nutrient composition (air-dried basis, %)

[0022]

[0023] Table 2. Effects of UDCA feeding in late gestation on sow reproductive performance (n=12)

[0024]

[0025] Note: 1 IUGR pigs are defined as piglets with a birth weight of less than 1.1 kg; 2 The coefficient of variation (CV) is defined as the ratio of the standard deviation of the birth weight of piglets to their average birth weight.

[0026] Table 3. Effects of UDCA feeding in late gestation on weaning indicators of piglets at 28 days.

[0027]

[0028] Table 4. Dietary formulation and nutrient composition (air-dried basis, %)

[0029]

[0030]

[0031] Table 5. Effects of CDCA feeding in late gestation on sow reproductive performance (n=8)

[0032]

[0033] Note: 1 IUGR pigs are defined as piglets with a birth weight of less than 1.1 kg; 2 The coefficient of variation (CV) is defined as the ratio of the standard deviation of the birth weight of piglets to their average birth weight.

[0034] The above embodiments are only used to explain the technical solutions of this application and do not limit the scope of protection of this application.

Claims

The application of 1,3a,7β-dihydroxy-5β-cholestane-24-acid in the preparation of agents that reduce the incidence of intrauterine growth retardation in pregnant sow fetuses, wherein, The pregnant pigs referred to are those from 85 days of gestation until parturition.

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