RU2306944C1 - Method for early stimulation of reproductive cyclic recurrence in cows after delivery - Google Patents

Abstract

FIELD: animal science, veterinary obstetrics.

SUBSTANCE: cows should be subcutaneously injected with DSP (denaturated suspended placenta) at the dosage of 20 ml/cow/d during 10 d, not more, before delivery or immediately after delivery. The innovation enables to shorten the terms of service period at optimal fertilization in cows due to increasing the level of adaptational-metabolic homeostasis and activating neuroendocrine regulation of reproductive cyclic recurrence.

EFFECT: higher efficiency.

4 dwg, 7 tbl

Description

The present invention relates to the field of animal husbandry, in particular to veterinary obstetrics, and can be used in the prevention of infertility in cows after childbirth.

It is known that for the first time after childbirth, cows can come into a state of hunting already on the 30th day and fertilize by 65-77 days (Dowlen N., Richardson D. Reproductive management at the dairy experiment station. - Jersey J., 1977, v 24, No. 6. - p. 46; Kupferschmiedt N. Untersuchungen über die postpartale Rastzeit beim Rind. Schweizer Archiv für Tierheilkunde, 1975, Bd. 117, H.5. - S.243-254). By reducing the service period, the number of fertilized cows per year can be increased by about 5% (Kräusslich N. et. Al. Der Einfluss der Rastreit auf verschiedene Fruchtbarkeitsparameter. - Berl. Mid Munch. Tierarztl., Wschr., 1977, Bd.90. , H.3. - S.55-57).

Known methods for early stimulation of sexual cyclicity to reduce the service period by using hormonal drugs both separately and in combination with biogenic stimulants before and after childbirth (B. Semenov. Using various means and methods of sexual excitability of cows / B.Ya. Semenov / / In the book Questions of veterinary pharmacy and pharmacotherapy. - Riga. - 1982. - 284 pp .; VA Akatov. Effect of synestrol, estradiol dipropionate and oxytocin on uterine motility / V.A. Akatov, V.D. Misailov / / Veterinary medicine, 1970. - No. 2. - P.89-93; Gubarevich Y. G. The influence of some x medications for contractile activity of the uterus of cows / Ya.G. Gubarevich, V.M. Voskoboinikov // Issues of the theory and practice of veterinary medicine and livestock: Scientists of the West Vitebsk Institute // Minsk, Urodzhay, 1970. - t.22. - S.85-91).

The use of these methods without a preliminary study of hormonal status in animals can lead to negative consequences. In addition, these drugs have insufficient immunostimulating activity to increase the nonspecific resistance of the body of cows in the postpartum period (Osetrov A.A. System of indications and contraindications for the restoration, stimulation and synchronization of the reproductive function of cows and heifers / A.A. Osetrov // Republican Scientific. - production conference on the prevention of infertility and diseases of the mammary gland of farm animals // Kazan, 1984. - S.62-63).

There is also known a method of hormonal stimulation of sexual cyclicity in cows (Mingazov T.A. Fertilization of cows using hormonal drugs / T.A. Mingazov, L.V. Babysheva // Zootechny, 1994. - No. 5. - P.29-30) , which allows you to reduce the service period with anestrus by 20 days. This method does not increase the level of non-specific immunity in animals.

The objective of the invention is to improve the quality of stimulation of sexual cycles in cows in the early postpartum period.

This is achieved by the fact that an immunomodulator (RU 2036651, 5 А61К 31/00, 1995) is used as a stimulating agent - denatured suspended placenta (PDS). PDS is a tool that normalizes metabolic processes in the body that have an immunomodulating and adaptogenic effect due to the presence of polypeptides, amino acids and nucleic acids in its composition.

Due to the fact that the cows are complexly affected by a number of factors, including: the functional state of the reproductive system, feeding, maintenance, features of the use technology that cause, first of all, the disorder of the neuroendocrine regulation of sexual cycle (Ilyinsky E.V. Prevention of cow infertility in conditions of intensification of dairy cattle breeding / E.V. Ilyinsky // Krasnodar - 1983. - P.37-50; Sorra V., Bertoni J. Jnsufficiente fertilita bovina ja cause di natura alimentare / V. Coppa, J. Bertoni // Zootecnia e veterinaria, 1980. - v. 36, No. 11. - p. 9639-9646; Vallat Andre. Jnfecondite collective des bovines Aspects nutrionnels / A. Vallat // Science veterinary. - Medicine comparative. - 1982. - v.84. - No. 1. - p.37-49), then the introduction of the animal drug PDS will contribute to the formation of adaptive and metabolic homeostasis, increase natural resistance and activation of neuroendocrine regulation sexual cycles in cows.

A method is proposed for early stimulation of sexual cyclicity in cows by administering a bionormalizer before childbirth or immediately after childbirth, in which the animals are administered a PDS immunomodulator subcutaneously at a dose of 20 ml / goal / day (200 mg) for no more than 10 days.

Example. The first group of cows (35 goals) PDS was administered within 10 days before birth. Animals of the second group (38 goals) PDS was administered within 10 days after birth. The third group (41 goals) - control animals after childbirth, which were not subjected to processing.

The effectiveness of the drug was taken into account in terms of reproductive function in cows.

As a result, it was noted (Table 1) that in the 1st group, with a 10-day treatment of PDS cows 10 days before the expected birth, the arrival in the hunt averaged 19.5 days. At the same time, 27 goals were fertilized after the first, 4 goals after the second, 2 goals after the third and 2 goals after the fourth insemination. Fertility during the observation period - 64 days after treatment was 100% (35 goals).

In the second group, when PDS was processed for 10 days immediately after childbirth, the arrival in the hunt for the group averaged 15.0 days. At the same time, 34 goals were fertilized after the first, 3 goals after the second and 1 goal after the third insemination. Over the observation period 49 days after PDS treatment, fertility was 100% (38 goals).

In the third group (control), the arrival in the hunt was 63 days. Fertility during the observation period of 71 days was 100% (41 goals). Thus, the best effect on the stimulation of sexual cyclicity in the early postpartum period was noted in the 2nd group, since the time of cows coming to the hunt was the smallest at high fertility and the lowest insemination index.

Table 1
The effectiveness of various applications of the MPD Group number Number of animals PDS administration time The appearance of sexual cyclicity, days (average) Number of inseminations, goal Fruitful insemination, in a day Insemination index Fertilized, goal% one 2 3 four one 35 Before giving birth 19.5 27 four 2 2 64.1 1.4 35 (100) 2 38 After childbirth 15.0 34 3 one - 49.5 1,1 38 (100) 3 41 63.0 21 eleven 5 four 71.3 1,5 41 (100)

1) Blood for determination of serum estradiol, progesterone, cortisol, characterizing the degree of activity of neuroendocrine regulation of sexual cyclicity, as well as indicators of albumin, α-, β-, γ-globulins and immunoglobulins, β-lipoproteins, cholesterol, amylase activity, alanine aminotransferase ( AlAT), aspartate aminotransferase (AsAT), alkaline phosphatase (ALP), reflecting the level of adaptive and metabolic changes, were taken from the jugular vein in cows before and after PDS treatment 10 days before delivery (group 1) and similarly when treated PDS during 10 days immediately after birth (2nd group). As a control, intact animals were used, in which blood was sampled and determined at the same time.

The obtained hormone content data (Tables 2, 3) when using PDS within 10 days before childbirth showed that the progesterone concentration immediately after childbirth decreases 3 times more than in the control. The decrease in estradiol concentration was also more pronounced after PDS treatment compared with control animals, which indicates the activity of the fetoplacental system and is one of the dominant factors in the onset of labor (I. Mitrofanov. Change in immunity indicators during the normal menstrual cycle / I. A. Mitrofanov // Obstetrics and Gynecology, 1984. - No. 3. - P.8-9).

Treatment of PDS cows immediately after birth in a similar dose showed that after the end of the stimulation course there was a tendency to increase estradiol against its unchanged state in the control. This indicates the intensification of the processes of folliculogenesis and uterine blood flow, since a decrease in the level of estradiol is characteristic of its disorders (Burlev V.A. // Bulletin of the Academy of Veterinary Sciences of the USSR, 1990. - No. 5. - S.10-14).

Thus, luteo-inhibiting processes that contribute to a decrease in progesterone and an increase in estradiol in the blood occur, obviously, due to the presence of low molecular weight polypeptides in the composition of the tested preparations, which have a certain activity with respect to induction by the cell membrane of arachidonate (arachidonic acid), which by a number of biochemical reactions turns into prostaglandins (Guidance on immunopharmacology: Transl. from English / Ed. by M. M. Dale and J.K. Formen. - M .: Medicine, 1998. - 332 p.).

In this case, a decrease in progesterone levels is associated with the induction of PDS of prostaglandins that actively cause lysis of the corpus luteum of the genital cycle.

An increase in the level of estradiol - 17β (during treatment after childbirth), obviously indicates an increase in the processes of inhibition of lipid peroxidation of the membranes and mitochondria of the cell, which leads to an increase in their transport functions, activity of enzyme systems, as well as substrate specificity.

table 2
Hormonal blood counts of cows during PDS treatment for 10 days before delivery Blood sampling time (n-4) Estradiol, nmol / L Progesterone, nmol / L Cortisol, nmol / L experience the control experience the control experience the control 1. 3a 10 days before delivery (before treatment) 4.73 ± 0.40 3.80 ± 0.83 20.25 ± 5.08 16.85 ± 2.69 32.18 ± 11.48 20.20 ± 2.78 2. After childbirth, on the 2nd day 2.64 ± 1.44 4.12 ± 1.02 0.84 ± 0.20 2.20 ± 0.96 37.33 ± 11.70 28.88 ± 4.44 3. 24 days after delivery 4.89 ± 0.25 4.95 ± 0.16 0.68 ± 0.08 1.83 ± 1.03 27.50 ± 2.47 22.75 ± 3.31

Table 3
Hormonal blood counts of cows during PDS treatment within 10 days after delivery Blood Take Time (n = 4) Estradiol, nmol / L Progesterone, nmol / L Cortisol, nmol / L experience the control experience the control experience the control 1. After delivery (before treatment) 2.99 ± 1.07 2.90 ± 1.29 1.31 ± 0.66 0.71 ± 0.13 41.50 ± 11.11 21.93 ± 2.91 2. 10 days after the start of PDS processing 3.91 ± 0.71 4.57 ± 0.70 1.00 ± 0.47 0.64 ± 0.04 36.33 ± 12.82 21.43 ± 4.60 3. 24 days after the start of PDS processing 4.82 ± 0.32 4.89 ± 0.25 0.63 ± 0.07 1.48 ± 0.56 46.53 ± 3.43 36.63 ± 9.53

Considering that estradiol-17β is capable of being converted into estriol in the body, it should be assumed that its increase during the treatment of cows with PDS after childbirth contributes to the appearance of the most pronounced stimulating effect on the proliferative activity of the cervix, vagina and vulva.

The tendency of an increase in the level of cortisol in animals treated with PDS within 10 days before birth indicates the activation of the pituitary-adrenal system of the mother and the fetus through increased secretion of adrenocorticotropic hormone (ACTH) and releasing hormone of the hypothalamus (I. Makarov, On the functional state of the pituitary adrenal system during normal pregnancy / I.A. Makarov // Obstetrics and gynecology, 1981. - No. 5. - P.30-31).

In connection with the foregoing, the mechanism of the bio-normalizing effect of PDS on the stimulation of sexual cyclicity in the early postpartum period occurs due to the removal of the inhibitory effect of progesterone, as a result of which hypothalamic-pituitary bonds are activated, folliculogenesis develops and, at the same time, the level of estrogen increases in the blood.

2) At the same time, biochemical studies of humoral indicators of the level of metabolic processes and natural resistance in cows show that after the introduction of PDS 10 days before the birth, the most pronounced changes were noted in relation to β-globulins, γ-globulins and total immunoglobulins (Table 4), where the increase in the concentration of the studied fractions was more intense in relation to the control. Changes in protein fractions during the processing of cows within 10 days after birth (Table 5) are characterized mainly by the same tendency for changes among themselves, as well as the similarity in the general direction of changes with control animals.

The activity of indicator serum enzymes characterizes the adaptive mechanism of mother cows and their ability in the future to manifest sexual repetition (Tables 6, 7).

Table 4
Changes in protein indicators in the blood of cows during PDS treatment for 10 days before delivery The content of protein fractions (n = 4) Albumin,% α-globulins,% β-globulins,% γ-globulins,% A / G Immunoglobulins, units experience the control experience the control experience the control experience the control experience the control experience the control 1. 10 days before delivery (before treatment) 42.79 ± 1.15 43.44 ± 2.34 14.54 ± 1.50 13.95 ± 1.53 16.54 ± 1.19 13.31 ± 0.61 26.13 ± 1.37 29.30 ± 1.90 0.74 0.77 25.28 ± 0.76 21.91 ± 1.62 2. After childbirth, on the 2nd day 41.05 ± 1.96 42.39 ± 2.34 15.86 ± 1.09 13.80 ± 1.15 15.44 ± 1.95 13.24 ± 0.94 27.65 ± 1.78 30.57 ± 2.32 0.70 0.74 24.78 ± 0.89 22.03 ± 1.66 3. 24 days after delivery 35.98 ± 1.94 41.17 ± 0.68 14.72 ± 1.15 13.04 ± 1.28 13.34 ± 1.45 13.32 ± 1.15 35.96 ± 2.03 32.47 ± 1.45 0.57 0.70 30.64 ± 2.22 23.56 ± 1.22 - p <0.05 (hereinafter)

Table 5
Changes in protein indicators in the blood of cows during PDS treatment within 10 days after delivery The content of protein fractions (n = 4) Albumin,% α-globulins,% β-globulins,% γ-globulins,% A / G Immunoglobulins, units experience the control experience the control experience the control experience the control experience the control experience the control 1. On the 2nd day after birth 46.01 ± 1.14 43.38 ± 1.40 14.15 ± 0.02 15.08 ± 1.03 13.63 ± 3.37 16.18 ± 0.96 26.21 ± 1.50 25.36 ± 1.23 0.85 0.77 21.47 ± 1.45 20.99 ± 3.57 2. 10 days after the start of PDS processing 42.24 ± 1.86 41.80 ± 2.87 15.84 ± 1.19 15.67 ± 0.59 14.72 ± 1.23 13.83 ± 1.64 27.20 ± 2.30 28.70 ± 1.65 0.73 0.72 22.23 ± 0.25 25.17 ± 2.79 3. Blood levels 24 days after birth 41.05 ± 0.95 38.25 ± 1.17 15.46 ± 1.03 14.58 ± 1.18 12.94 ± 0.54 14.02 ± 0.87 30.55 ± 1.96 34.15 ± 1.60 0.70 0.61 27.73 ± 2.01 26.86 ± 4.07

Table 6
Enzymatic activity of blood of cows when processing PDS for 10 days before childbirth Enzyme activity (n = 4) Amylase, mg / h × L Alkaline phosphatase, nmol / s × l Alanine aminotransferase, μmol / L Aspartate aminotransferase, μmol / L experience the control experience the control experience the control experience the control 1. 10 days before delivery (before treatment) 11.38 ± 1.07 13.60 ± 1.55 512.08 ± 132.95 648.65 ± 30.11 0.40 ± 0.01 0.42 ± 0.08 0.84 ± 0.08 1.01 ± 0.09 2. After childbirth, on the 2nd day 21.25 ± 4.29 17.20 ± 2.58 500.8 ± 78.78 593.58 ± 70.13 0.28 ± 0.07 0.35 ± 0.05 0.70 ± 0.03 0.68 ± 0.16 3. 24 days after delivery 12.25 ± 2.35 15.43 ± 3.06 545.00 ± 98.67 327.65 ± 78.43 0.44 ± 0.19 0.48 ± 0.16 0.97 ± 0.12 0.94 ± 0.10

Table 7
Enzymatic activity of blood of cows during PDS treatment within 10 days after delivery Enzyme Activity (n-4) Amylase, mg / h × L Alkaline phosphatase, nmol / s × l Alanine aminotrasferase, μmol / L Aspartate aminotransferase, μmol / L experience the control experience the control experience the control experience the control 1. On the 2nd day after birth 18.73 ± 5.73 17.93 ± 5.20 626.48 ± 143.47 328.58 ± 93.85 0.62 ± 0.07 0.48 ± 0.03 1.24 ± 0.24 0.94 ± 0.11 2. 10 days after the start of PDS processing 12.60 ± 1.35 19.58 ± 1.84 330.98 ± 14.01 319.93 ± 29.58 0.26 ± 0.07 0.26 ± 0.06 0.96 ± 0.13 0.80 ± 0.07 3. 24 days after the start of PDS processing 28.03 ± 1.91 13.78 ± 1.81 572.60 ± 126.27 412.38 ± 96.99 0.32 ± 0.07 0.39 ± 0.06 0.86 ± 0.08 0.79 ± 0.06

It is known (Golikov P.P. Activity of indicator serum enzymes as an indicator of disorders of oxygen homeostasis in patients with emergency conditions. / P.P. Golikov // Pat. Physiology and Experimental Therapy, 1986. - No. 6. - P.60-64 ) that the stressful situation for the body that occurs during childbirth is accompanied by a switch of carbohydrate metabolism to lipid metabolism due to glucocorticoids, and a change in the hormonal background of the body increases the membrane permeability. The glucose level, in turn, also depends on the activity of AlAT and AcAT, and the glucose-alanine transition is activated by dephosphorylation of alkaline phosphatase. In the experiments, changes in the enzymatic activity when using PDS in childbirth are characterized by a tendency toward an increase in alkaline phosphatase, amylase, and AsAT. An increase in alkaline phosphatase activity is obviously associated with the release of glucose from tissues after dephosphorylation. In turn, an increase in the activity of AcAT can be explained by a more significant intensity and the relationship of protein, carbohydrate and lipid metabolism. Against the background of relative hypoproteinemia, an increase in AlAT activity can also be considered as an increase in the alanine glucose pathway with the release of glucose from cells due to its dephosphorylation by increased alkaline phosphatase activity, i.e., as a metabolic block syndrome with respect to glucose and activation of compensatory synthesis pathways with respect to proteins. In general, the activity of indicator blood enzymes reflects the active state of the body's homeostasis in the initial stages of its violation.

3) Histostructural changes in the ovaries of cows after PDS treatment show that in the cortical layer there are whole generations of follicles at different stages of development (Fig. 1). Intensive resorption of the white body 1 is observed, secondary follicles 2 are noted. The greatest number of follicles and ova maturing with a large cavity was greatest. Such a picture is typical for an organ subjected to a stimulating load, when a certain positive relationship is revealed between the follicle size and the concentration of steroid hormones in the follicular fluid (T. Torganova, Relative autonomy of steroid and oogenesis in a woman’s ovarian follicle / I.T.Torganova // Obstetrics and gynecology, 1983. - No. 2. - S.15-17). About the bio-normalizing effect of PDS is indicated by the phenomena of hyperplasia in the lymph nodes noted by us (Fig. 2), where the reticular tissue 3 and the meat cords 4 are clearly expressed; an increase in the number of follicles 5 and reproduction centers 6 of the spleen (figure 3); plethora of sinuses and veins, as well as vacuolization of hepatocytes in the liver (Fig. 4), in which hepatic trabeculae (beams) 7, triads of the liver 8, consisting of the interlobular artery 9, interlobular (bile) glomerulus 10 and interlobular vein 11, as well as hepatocytes 12.

Feasibility

The economic efficiency of the use of PDS during treatment at a dose of 20 ml / goal / day for 10 days before the expected birth amounted to 78.0 rubles, and when treated in the same dose for 10 days after delivery, it amounted to 91.7 rubles. 1 ruble of costs, respectively (in 2005 prices).

Information sources

1. Dowlen H., Richardson D. Reproductive management at the dairy experiment station. - Jersey J., 1977, v. 24, No. 6. - p. 46.

2. Kupferschmiedt H. Untersuchungen über die postpartale Rastzeit beim Rind. Schweizer Archiv für Tierheilkunde, 1975, Bd. 117, H.5. - S.243-254.

3. Krüusslich H. et. al. Der Einfluss der Rastreit auf verschiedene Fruchtbarkeitsparameter. - Berl. und munch. Tierarztl., Wschr., 1977, Bd. 90, H.3. - S. 55-57.

4. Semenov B.Ya. The use of various means and methods of sexual excitability of cows / B.Ya. Semenov // In the book. Questions of veterinary pharmacy and pharmacotherapy. - Riga. - 1982. - 284 p.

5. Akatov V.A. The effect of sinestrol, estradiol dipropionate and oxytocin on uterine motility / V.A. Akatov, V. D. Misailov // Veterinary medicine, 1970. - No. 2. - S. 89-93.

6. Gubarevich Ya.G. The effect of certain medications on the contractile activity of the uterus of cows / Ya.G. Gubarevich, V.M. Voskoboinikov // Vopr. theory and practice of veterinary medicine and livestock: Scientists app. Vitebsk Vet. in-that. // Minsk, Urodzhay, 1970 .-- v.22. - S.85-91.

7. Osetrov A.A. The system of indications and contraindications for the restoration, stimulation and synchronization of the reproductive function of cows and heifers / A.A. Osetrov // Republican Scientific. - production. conf. On the prevention of infertility and diseases of the mammary gland of farm animals // Kazan, 1984. - S.62-63.

8. Mingazov TA. Fertilization of cows using hormonal preparations / T.A. Mingazov, L.V. Babysheva // Zootechny, 1994. - No. 5. - S.29-30.

9. RU 2036651, 5 A61K 31/00, 1995.

10. Ilyinsky E.V. Prevention of cow infertility in conditions of intensification of dairy cattle breeding / E.V. Ilyinsky // Krasnodar. - 1983 .-- S.37-50.

11. Sorra V., Bertoni J. Jnsufficiente fertilita bovina ja cause di natura alimentare / V. Sorra, J. Bertoni // Zootecnia e veterinaria, 1980. - v. 36, No. 11. - p. 9639-9646.

12. Vallat Atldre. Jnfecondite collective des bovines Aspects nutrioimels / A.Vallat // Science veterinary. - Medicine comparative. - 1982. - v. 84. - No. 1. - p. 37-49.

13. Mitrofanov I.A. Change in immunity indicators during the normal menstrual cycle / I.A. Mitrofanov // Obstetrics and gynecology, 1984. - No. 3. - S.8-9.

14. Burlev V.A. // Bulletin of the Academy Vet. Sciences of the USSR, 1990. - No. 5. - S.10-14.

15. Guidance on immunopharmacology: Per. from English / Ed. M.M.Dale and J.K. Formen. - M.: Medicine, 1998 .-- 332 p.

16. Makarov I.A. On the functional state of the pituitary-adrenal system during normal pregnancy / I.A. Makarov // Obstetrics and Gynecology, 1981. - No. 5. - S.30-31.

17. Golikov P.P. The activity of indicator serum enzymes as an indicator of disorders of oxygen homeostasis in patients with emergency conditions. / P.P. Golikov // Pat. physiology and experimental therapy, 1986. - No. 6. - S.60-64.

18. Torganova I.T. About the relative autonomy of steroid and oogenesis in a woman’s ovarian follicle / I.T.Torganova // Obstetrics and gynecology, 1983. - No. 2. - S.15-17.

Claims (1)

A method for early stimulation of sexual cyclicity in cows after childbirth by administering a bionormalizer, characterized in that before the birth or immediately after the birth, the cow is given an immunomodulator PDS (denatured suspended placenta) subcutaneously at a dose of 20 ml / head / day (200 mg) for no more than 10 days.

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