Anestrus in Dairy Animals: Prevention and Treatment

Anestrus in Dairy Animals: Prevention and Treatment

Manisha Sethi¹, Hitesh K. Bagri², Nadeem Shah³*, Mukesh Bhakat⁴, Tushar K Mohanty⁵

¹MVSc (Animal Reproduction, Gynaecology and Obstetrics)

²MVSc Scholar (Animal Reproduction, Gynaecology and Obstetrics)

³PhD Scholar (Animal Reproduction, Gynaecology and Obstetrics)

⁴Principal Scientist (Livestock Production and Management)

⁵Principal Scientist (Animal Reproduction, Gynaecology and Obstetrics)

Artificial Breeding Research Centre, ICAR-National Dairy Research Institute (NDRI), Karnal-132001 (Haryana), India

*drnadeem.ndri@gmail.com

Anestrus is a broad term that indicates the lack of expression of estrus (or absence of estrous signs), despite efficient estrus detection. Anestrus is usually characterized by a lack of ovarian progesterone production. It is caused by many factors such as under nutrition, reduction in body condition score, suckling calf, lactation, dystocia, uterine pathology, debilitating disease etc. Treatment involves improvement in energy status i.e. providing optimal nutrition during the transition period and during early lactation and use of various hormones such as estrogen, progesterone, GnRH, PMSG etc.

Introduction:

Anestrus is a reproductive cycle functional abnormality characterised by the absence of overt signs of estrus manifested either by a lack of expression of estrus or by a failure to detect estrus. In animals, physiological anestrus is seen during prepubertal period, pregnancy, lactation, as well as during early postpartum period. Pathological anestrus can result from disruption of the reproductive axis and may be associated with uterine pathology such as pyometra, fetal resorption, maceration and mummification. Anestrus is caused by a variety of factors, but its prevalence indicates a lack of nutrition, environmental stress, uterine pathology, and poor management practises. The condition is diagnosed by looking at the various causal variables that contribute to it. Despite the fact that various treatment agents (hormonal and non-hormonal) have been used, there is no one solution to solve the problem.

Causes and Risk Factors

1. Nutrition: Animal’s nutrition status has an impact on follicular growth, maturation, and ovulation. (Diskin et al., 2003). One of the most common causes of anestrus in heifers is malnutrition. Shortage of feed and good quality fodder leads to an extended postpartum period of anestrus (>150 days) in cattle of tropical area. Following parturition, animal has high metabolic load because of milk production. If there is shortage of feed during this transition period of the animal, it will lead to negative energy balance (NEB) which will ultimately affect the follicular growth and will hamper the normal cyclic events of the animal. Anestrus is also linked to mineral deficiencies such as calcium (Ca), phosphorus (P), copper (Cu), zinc (Zn), and manganese (Mn). Minerals play an intermediate role in the activity of hormones and enzymes at the cellular level, and their shortage has been shown to impact female reproduction rates.
2. Body Condition Score (BCS): Body condition score is a measurement that assesses an animal’s nutritional health and is a key component in determining reproductive success. Pre–calving, calving, and early postpartum BCS extremes (very low and very high) delay the onset of cyclicity. BCS at calving, on the other hand, is a greater predictor of postpartum cyclicity resumption than prepartum BCS. At calving, a BCS of 3.5 (on a five-point scale) is required for optimal reproductive function (Shah et al., 2021). Feed restriction during late pregnancy and the early postpartum period results in reduced BCS, which contributes to extended postpartum anestrus.
3. Management factors

a). Lameness: One of the main causes for decreased reproductive performance, output potential, and increased culling rate of affected cows has been their increased vulnerability to certain diseases, including lameness. It has been reported that delay in ovarian activity in earlier postpartum is correlated with lameness and lame cows take 12 days longer to get pregnant as compared to their non-lame counterparts.

b). Milk production: Expression of estrus can be altered obviously during the period of high milk yielding due to totally an unknown mechanism. There is a negative association between milk period and duration of estrus expression and milk productivity.

c). Endocrine hormones: Many studies have suggested that endocrine balances are necessary for maintaining normal estrus and re-establishing fertility following calving. Estrus expression induced by adequate endogenous estradiol production can cause the standing response in cattle. It was found that high levels of estradiol at the end of pregnancy can make a cow refractory to estrus in following normal ovulation, and it was suggested that progesterone treatment prior to the first postpartum ovulation can re-sensitize the brain and allow for estrus to be expressed. In terms of other hormones, gonadotropin releasing hormone (GnRH) can induce leuteal hormone (LH) to be released in estrus range cows, and treatment with 1,000 or 2,000 IU pregnant mare serum gonadotropin (PMSG) can cause ovarian activity to be initiated (Sethi et al., 2021).

4. Environmental Stress: The development of follicles and the appearance of estrus are affected by environmental stress (severe cold and heat). Heat stress significantly reduces ovarian activity, which results in anestrus. Heat stress affects folliculogenesis, follicular fluid micro environment and oocyte quality. Also any form of stress causes, decline in feed intake which results in reduced secretion of gonadotrophins. Furthermore, high ambient temperatures produce hyperprolactinemia and decrease gonadotrophin secretion, resulting in changes in ovarian folliculogenesis and steroidogenesis.
5. Lactation High yielding cattle and buffalo shows significantly longer postpartum anestrus period or weaker signs of estrus. This is because of prolactin secretion which is anti gonadogrophic.
6. Suckling Suckling reduces postpartum ovarian activity, resulting in a longer duration of postpartum anestrus. Suckled beef cows have a longer postpartum anestrus than milked dairy cows. Suckling increases the release of prolactin, cortisol, and oxytocin, all of which have a detrimental influence on the GnRH–LH axis. Higher levels of these hormones limit GnRH secretion while increasing the concentration of endogenous opioid peptides; as a result, endorphin reduces LH pulse frequency, delaying the start of postpartum cyclicity.
7. Parasitic Infestations One of the stressful conditions is heavy parasitism, which is more common in growing cattle than in adult cattle. Parasitic infections in animals, such as fascioliasis, theleriosis, schistosomiasis, and trypanosomiasis, induce anaemia and weight loss, which leads to anestrus.

Treatment

1. Hormonal Treatments:
2. Estrogens Based Treatment: Because of its positive feedback effect over the pituitary for LH surge, oestrogen treatment causes expression of estrus and ovulation in the presence of dominant follicles. As a result, it has been used to promote ovulation and shorten the postpartum anestrus phase. In the absence of a dominant follicle, oestrogen causes anovulatory estrus. Estrogens have also been demonstrated to promote luteolysis in ruminants most likely by boosting endometrial prostaglandin secretion while concurrently lowering circulating LH levels.
3. Progesterone Based Treatment: Exogenous progesterone induces a negative feedback effect on LH release in the brain and pituitary, simulating the luteal phase of the estrus cycle. The normal follicular phase of the cycle is stimulated when progesterone is removed from the cycle. However, a dramatic reduction in progesterone levels at the end of treatment is required for such treatment to appear beneficial. PRID (progesterone–releasing intravaginal device), CIDR (controlled internal drug release), and CueMate (intravaginal progesterone–releasing intravaginal device) are all effective in restoring cyclicity in anestrus animals. The concentration of progesterone drops sharply after withdrawal, and estrus and ovulation occur between 2– 8 days following stopping medication.
4. Gonadotropic Releasing Hormone (GnRH) Based Treatment: The single intramuscular injection of GnRH analogue (10 to 20µg Buserelin) has been used effective in induction of estrus and concurrent ovulation with variable response (45.5 to 87.5%) within 4–22 days. The variable response may be due to differential action of GnRH on different stages of follicular development. It induces ovulation, if mature follicle is present at the time of administration by inducing the LH surge. On the contrary, it stimulate emergence of new follicular wave through enhanced secretion of FSH, thus effective in long term. Pulsatile/intermittent injections of small dose of GnRH (at every 2 hours, intravenously) has been tried in order to induce LH pulses.
5. Pregnant mare serum gonadotrophin (PMSG): Because of its main FSH-like activity, pregnant mare serum gonadotrophin (PMSG) or equine chorionic gonadotrophin (eCG) is a potent activator of ovarian activity. As a result, it’s been widely utilised to induce superovulation. Anestrus calves and buffaloes have been successfully treated with a single intramuscular injection at modest doses, either alone or in combination with others. Human chorionic gonadotrophin (hCG) has also been used successfully in the treatment of anestrus (Sethi et al., 2021).
6. Treatment with Prostaglandins: The treatment of choice for persistent corpus luteum and sub estrus is prostaglandin (PGF2). A single dosage of a natural or synthetic counterpart of PGF2 has been used to regulate silent estrus in cattle and buffaloes with reasonable success. It’s important to remember that PGF2 is only effective during days 6–16 of the cycle and when the corpus luteum is active. In both cattle and buffaloes, an intramuscular injection of 25mg (total dose) of natural PGF2 or 250 to 500 mcg of synthetic PGF2 is necessary to regress the CL. However, a lesser dose of PGF2 (5 mg) is similarly effective in regressing CL by intra– vulvo–submucosal (IVSM) injections.
7. 2. Non Hormonal Treatments
8. Plant Based Heat Inducers: Plants produce a variety of phytochemicals such as alkaloids, glycosides, terpenes, and tannins (secondary metabolites) as part of their normal metabolic activity, many of which have medicinal qualities when consumed by animals. Many plants are high in vitamins and minerals, and some have estrogenic properties that can help anestrus animals regain their cyclicity. Several plants, including Murraya koenigii (curry leaves), Nigella sativa (kalonji), Abroma augusta (Ulatkambal), Saraca asoca (Ashoka), Trigonella foenum–graecum (Methi), Bambusa aruninacea, Carica papaya, Asparagus recemosus, Leptadenia reticulate, Courupita guianesis, Prajana HS (Indian Herbs), Janova (Dabur), Sajani (Sarabhai), Heat up (Century), Heat raj (Ranjan), Fertivet (Ar Ex Labs), and Aloes compounds (Alarsar) are commercially available and efficient in restoring cyclicity with indigenous herbal formulations.
9. Utero–Ovarian Massage: The oldest, simplest, cheapest, and most successful way of inducing estrus in anestrus cattle and buffaloes is utero–ovarian massage. The exact method by which ovarian massage produces cyclicity is unknown, but it is thought to involve the activation of intrinsic intra–ovarian factors, as well as an increase in blood circulation to the ovaries and uterus, which enhances hormone and growth factor availability.
10. Lugol’s Iodine: Lugol’s iodine treatment is cheaper and effective means of management of anestrus but response has been variable (45 to 91.7%) among cattle and buffaloes. Lugol’s iodine solution (5%) has traditionally been used as a cervical paint. It is presumed that painting of Lugol’s iodine on posterior part of the cervix causes local irritation and brings about reflux stimulation at anterior pituitary for secretion of gonadotrophins and consequently cyclicity. Lugol’s iodine is an irritating solution and intrauterine infusion of Lugol’s solution (0.5 to 1.0%) causes hyperemia (enhanced circulation) of uterine mucosa resulting into degree of iodine absorption from uterus. The absorbed iodine probably increases the metabolic rate of body through stimulating the thyroid hormone secretion. Increased metabolic rate trigger the ovarian functions by enhancing the energy utilization.

Conclusion: As such there is no single panacea to correct anestrus. Further, research is needed especially at cellular and molecular level for better understanding of its etiology, diagnosis and therapeutics.

References:

Sethi, M., Shah, N., Mohanty, T. K., Bhakat, M., Dewry, R. K., Yadav, D. K., Gupta, V.K. and Nath, S. (2021). The Induction of Cyclicity in Postpartum Anestrus Buffaloes: A Review. Journal of Experimental Zoology, India, 24(2), 989-997

Shah, N., Sethi, M., Kumar, P., Mohanty, T. K., Bhakat, M., Dewry, R. K., Sarkar, D., Gupta, V.K. and Soe, A. (2021). Selection of Heifers and Breeding Bulls for Reducing Calving Difficulties in the First Calvers: An Overview. The Indian Journal of Veterinary Sciences and Biotechnology, 17(02), 1-8.

 https://www.pashudhanpraharee.com/therapeutic-management-of-anoestrus-in-dairy-cattle-in-india/

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