Minerals, serum metabolites, hormones, and bovine reproduction: a review

Abstract

This study aimed to highlight the roles of different minerals, serum metabolites, and hormones related to reproductive health of cattle as these have a significant role in cattle production and reproduction. Minerals are known for their contribution to several physiological processes such as cell formation and are paramount for physiological functions of vitamins, enzymes, and hormones. Evaluations of serum metabolites are good indicators of disease diagnosis and nutritional status in animals. Hormonal imbalance before and during pregnancy can negatively impact an overall bovine reproductive health. Minerals are important for reproduction, serum metabolites are a reliable indicator as their changes have been related to many disorders in reproduction, and hormones are significant indicators in cows presenting different reproductive conditions.

Introduction

Minerals are structural components of the body (Velladurai et al., 2016). They are also defined as inorganic substances found in all body tissues and fluids (Soetan et al., 2010). In animals, minerals are essential for various biological processes including growth, reproductive health, gestation progression, foetal development, lactation, and neonate calf health (Van Emon et al., 2020). They can be classified into macro (major) and micro (trace) elements (Kumar, 2015). Macro-minerals are the compounds required in large quantities, while micro-minerals are needed in small amounts (Al-Ghareebawi et al., 2017). There is also a third category of minerals called ultra-trace elements (Velladurai et al., 2016). According to Murray et al. (2000), macro-minerals are required in quantities above 100 mg/dl, while micro-mineral are required in quantities below 100 mg/dl. The ultra-trace minerals are required in amounts less than 1 mg/day (Tako, 2019).

The macro-mineral class comprises phosphorus (P), magnesium (Mg), calcium (Ca), sodium chloride, and potassium chloride, whereas micro-elements include iron (Fe), copper (Cu), cobalt, iodine (I), zinc, manganese, molybdenum, fluoride, chromium, selenium (Se), and sulphur (Sujayil and Dhanaraj, 2017). The ultra-trace elements include boron, silicon, arsenic, and nickel, which have been found in animals and are believed to be essential (Singaravadivel and Santhanaraj, 2017). Other minerals such as cadmium, lead, tin, lithium, and vanadium are not essentially required as there is weak evidence of their essentialness and they have no known nutritional contribution in animals (Soetan et al., 2010; World Health Organization, 2005).

Serum metabolites that can be used to measure reproductive health in cows include urea/blood urea nitrogen (BUN), creatinine (Cr), aspartate aminotransferase, alanine aminotransferase, Ca, total protein (TP), albumin (ALB), globulin, cholesterol (CHOL), glucose, minerals, and non-esterified fatty acids (Magnus and Lali, 2009; Ndlovu et al., 2007). Animal physiology, age, nutritional status, breed, and the change in season may affect changes in serum metabolite (Ndlovu et al., 2007). The incidence of postpartum disorders such as infertility and abortions may increase due to low concentrations of urea nitrogen, ALB, and CHOL, as well as low body condition scores (Molefe and Mwanza, 2020a; Utama et al., 2018). The incidence of dystocia, vaginal prolapse, retained placenta, downer cow syndrome, and generally poor reproductive performance in female bovines has been related to metabolite abnormalities. (Molefe and Mwanza, 2020b). The balance in metabolic indicators is key to the proper functioning of the reproductive system and necessary to increase livestock production.

In animal health, the assessment of hormones has been increasingly used to monitor negative changes associated with cow reproduction (Zhang et al., 2018). Previous research has identified a positive relationship between postpartum reproductive efficiency and metabolic hormones in cattle (Samadi et al., 2013). Predisposition to metabolic disorders may result from biological alterations in the neuro-hormonal system, which may lead to impaired immune function (Dudhatra et al., 2012). Due to the endocrinal and metabolic alterations known to suppress the uterine defence mechanism, the incidence of metabolic disorders is increasing in cattle (Kim et al., 2005; Mateus et al., 2002). Therefore, this review focuses on metabolic changes and how serum metabolites, minerals, and hormones relate to uterine defence.

Minerals in bovine reproduction

Calcium

Ca is an essential macronutrient required by the body (Harper, 2017). It is needed in large amounts in both animals and humans (Martinez et al., 2016). Approximately 99% of Ca is present in the skeleton and it is also known to be the most available mineral in the body (Trailokya et al., 2017). Nevertheless, a lesser percentage of Ca in the body outside the skeleton is found in the blood and is important for survival (Suttle, 2010). Its functional properties include muscle contraction, nerve conduction, blood clotting, and maintaining healthy bones (Trailokya et al., 2017). Other imperative capacities of Ca include ensuring proper heart function, milk production, conservation or fortification of the skeleton, enzyme and hormone metabolism, intestinal development, the transmission of nerve impulses, and cell membrane protection (Fridjayanti and Dilaga, 2019). Moreover, reduced levels of Ca can make the placenta difficult to come out due to poor uterine contraction causing retained placenta in the animal.

During severe Ca decline, the homeostatic maintenance mechanism of blood Ca concentration causes the reabsorption of Ca from the bones, for that reason, consumption of adequate Ca is important to lessen undesirable effects (Trailokya et al., 2017). Osteoporosis is a metabolic ailment characterized by bone decalcification and a high rate of fracture, may also be seen in animals due to low Ca levels and the fight this Ca will be extracted from the bones, causing the bones to become weak and porous, and ultimately break (Soetan et al., 2010).

Low blood Ca predisposes cows to peri-parturient disorders, such as mastitis and ketosis (Sepúlveda-Varas et al., 2015). Reduced blood Ca concentrations are typically concurrent with increasing plasma Mg concentrations (Fikadu et al., 2016). Regulating muscle functioning is one the most important function of Ca, and any disturbance in the level of Ca such as that which is caused by high Mg levels can lead to conditions such as hypocalcaemia, dystocia, and stillborn calves in peripartum cows/heifers. Parturient paresis, or milk fever, in cows is associated with Ca metabolism. This illness usually occurs with the onset of profuse lactation and the most common abnormality is acute hypocalcaemia with a decline in blood Ca level from normal (Soetan et al., 2010).

Research has shown that high-parity Jersey cows are more prone to hypocalcaemia and heifers rarely experience milk fever (Roche and Berry, 2006). Moreover, Ca requirements change depending on animal age and production status (Mokolopi and Beighle, 2006). Jersey breeds are high-producing cows and widely selected due to their high milk fat content (Chiwome et al., 2017). Due to the increased demand for Ca at parturition and the high milk production during lactation, the ability to extract Ca from the bone decreases with age (Krehbiel 2014). That may elucidate the infrequent rates of hypocalcaemia in heifers as compared to high-parity cows.

Also, high-yielding cows required more energy to support milk production and were more likely to have severe energy deficiency after calving than low-yielding cows (Chiwome et al., 2017). Therefore, higher milk yields are associated with a higher risk of developing metabolic disorders. In an epidemiological study by Lean et al. (2006), the authors have shown that the incidence of low blood Ca occurs frequently in Jersey cows than in other dairy cows and this may be due to the high milk yield in Jersey cows. These authors also reported that there is a 2, 25 times greater risk of hypocalcaemia in Jersey breeds when related to Holstein-Friesian cows. The incidence of milk fever in Jersey breeds was significantly (P < 0.05) more frequent in high-parity (fourth) cows (24.85%) compared to the second (5.90%), third (6.49%), and fourth (8.73%) parities (Chiwome et al., 2017).

Feeding Ca-rich diet to cows and heifers is an important way to provide correct daily consumption, and in animals that do not obtain sufficient Ca from the feed, supplementation should be used to increase Ca supply (Trailokya et al., 2017). A sufficient Ca supply can greatly boost reproductive output and body weight providing better oestrous physiological conditions for grazing bovines (Zhou et al., 2021).

Magnesium

Mg is the second most abundant intracellular divalent cation (Blaine et al., 2014). Several enzymes rely mainly on intracellular Mg for the regulation of their metabolism (Mahon et al., 2003). Nerve transmission is one of the most important functional characteristics of intracellular Mg (Wang et al., 2017). In mature ruminants, Mg absorption has two mechanisms in which it can occur, the first being the most important and which is dependent on potential difference above the rumen epithelium and occurs in the transference during low Mg levels (Blaine et al., 2014). The second mechanism is characterized by Mg transport over the epithelium with no dependency on the potential differences (Martens and Schweigel, 2000).

Deficient Mg absorption hinders the bovine’s capacity to stimulate stored Mg from bones, which is required for sustaining Mg concentrations in cells and the fluids outside the cells (Kronqvist et al., 2011). Low concentrations of potassium prevent the uptake of Mg, while ammonia levels in the rumen stimulate Mg uptake (Blaine et al., 2014). Research has also shown that when Mg levels increase, there is a decline in plasma Ca concentrations during calving (Goff et al., 2002a), this can cause difficult birth due to poor muscle contractions and may also lead to milk fever as well as retained placenta during parturition. Clinical signs such as failure to express oestrus, low rates of conception, low calf birth weight, and abortions may result from Mg deficiency in cows (Musa et al., 2016). Other common observations of Mg deficits are that calves are born weak and deformed with enlarged joints and Arthrogryposis/contracture joints (Kreplin and Yaremcio, 2009).

Hypomagnesaemia is also known as grass tetany, winter tetany, and grass staggers depending on the conditions in which it may arise (Kronqvist et al., 2011). The deficiency of Mg in the cerebrospinal fluid can lead to death as a result of hypomagnesaemia and tetany (McCoy et al., 2001). Generally, the reproductive status of animals is not directly disturbed by Mg, which is due to its indirect proportional relations with Ca; hence, a disorder of any sort in Ca-P-Mg concentrations can affect reproduction (Velladurai et al., 2016).

Phosphorus

P is a vital nutrient required in all living organisms (Yang et al., 2017). P is frequently stated as a ‘fertility’ mineral (Fageria et al., 2017). It is the second most abundantly available mineral at percentages of about 80–85 in the skeleton; it also plays a role in enzyme transfer and metabolic reactions in the body (Velladurai et al., 2016). In animals, P has the most identified roles compared to other minerals in the body, mainly for tissue and bone development, milk production, and utilization of energy (Abrams and Atkinson, 2003). Phosphorus is the structural component of phospholipids and nucleic acids and is also significantly involved in the metabolism of energy, protein modification, and signalling transduction cascades (Yang et al., 2017).

P deficiency has been linked with clinical manifestations such as osteomalacia and stiffness (Bakunzi et al., 2012). Osteomalacia is a systemic metabolic bone disease that can lead to disturbance of the bone metabolism of adult animals. This impaired mineralization is primarily caused by hypophosphataemia and cattle with osteomalacia are predisposed to downer cow syndrome due to weak bones (Takedani et al., 2021). Cows and heifers need properly functioning skeletons to support the animal during pregnancy; hence, P deficiency can be related to reproductive disorders as the animal might not be able to withstand the changes in body mass during gestation due to weak bones.

A South African study of mineral content indicated that the P level in natural pastures is not adequate to improve productivity in communally reared cattle (Ateba and Beighle, 2011). In their research, they used 12 Friesian calves aged 1–3 years to examine the utility of layer chicken litter and yellow maize meal as sources of P in cattle by evaluating their concentration in faeces, blood, and bone (Ateba and Beighle, 2011). The results of their study also found that the P concentration in the bone for animals that received layer chicken litter was lower, which could have resulted from the fact that animals were pulling P out of the bone and putting it in the blood and faeces which was reflected by their concentrations.

Selenium

Se is an important component of enzyme systems and interacts with Vitamin E to prevent tissue damage (Atli et al., 2012). Detrimental effects associated with Se insufficiency in animals include low growth, poor health, and low fertility (Glombowsky et al., 2017). Embryonic death during the first month of pregnancy, retained placentas, mastitis, metritis, and low fertility have been reported in cattle with Se deficiency (Bohrer, 2017; Juárez et al., 2021; Pereira and Vicente, 2013). Other studies have also indicated that reproductive disorders associated with Se deficiency may also cause a decrease in milk quality during the perinatal period in cows (Al-Shaar et al., 2020; Garam et al., 2020).

As Se has a narrow margin of safety, toxicities are more commonly seen when compared to deficiencies in farm animals. Se deficiency is associated with weak offspring and cystic ovaries (Balamurugan et al., 2017; Omeje, 2016). Another study has associated Se insufficiency in cows and heifers with infertility and low disease resistance (Kreplin and Yaremcio, 2009). Research has indicated that supplementing cows with Se and Vitamin E controls the risk of retained placenta and reduces the services per conception to 1.54–2.05 (Balamurugan et al., 2017; Mee, 2004). Se supplementation also prevents oxidative stress from damaging cells and their membranes (Karaağaç et al., 2022). Additionally, Se supplements have been indicated to improve the quality of milk (Safonov, 2022)

Copper

Cu is an important micronutrient required for the normal functioning of body metabolism in animals (Xinhuan et al., 2017). Cu is known to influence reproductive performance, production, and growth in cows (Balamurugan et al., 2017). It plays essential roles in the immune system and it is also involved in several reactive proteins, enzyme cofactors, Cu–estrogen interactions, Cu–progesterone interactions, melanin pigmentation, Fe transportation, and cellular respiration (Balamurugan et al., 2017). Cu insufficiency has the same influence on reproduction as other mineral deficits predisposing cows to poor fertility and delayed puberty (Suttle, 2010). Additionally, central nervous system anomalies in calves, low conception rates, embryonic mortalities, delayed oestrus, and placental necrosis in cows/heifers may be seen as a result of Cu deficiencies (Lata and Mondal, 2021).

Additional indicators of low Cu concentration include increased incidences of retained placenta and repeat breeding (Kreplin and Yaremcio, 2009). Cu deficiency is also related to early embryonic death, reduced immune competency, decreased conception rate, low libido, lowered semen quality, severe testicular tissue damage, and bull sterility (Balamurugan et al., 2017). Cu deprivation in ruminants leads to ataxia, abnormal wool and hair pigmentation, anaemia, bone disorders, connective tissue disorders, cardiovascular disorders, diarrhoea, and disease susceptibility (Suttle, 2010).

Iron

Fe is required in every animal for maintaining natural processes, for example, oxygen transportation and electron transfer of enzymes (Sánchez et al., 2017). More than 50% of bodily Fe content is present in haemoglobin (National Research Council (NRC), 2000). Cellular uptake of Fe occurs in many tissues through a process called the transferrin cycle (Ladeira Courelas da Silva AR, 2017). Transferrin is a plentiful plasma protein that fixes two atoms of Fe having very high affinity and it functions to keep Fe soluble, consequently avoiding the precipitation of aqueous plasma fe3 + ions out of aqueous plasma (Molefe, 2016).

Fe distribution in foetal development is cell-mediated by the extraembryonic visceral endoderm and syncytiotrophoblast in the placenta (Lieu et al., 2001). In foetal development, the intra- placental transfer of Fe happens during gestation and it is actively involved in foetal growth, therefore, its deficiency may lead to foetal mortality (Andrews et al., 2005). Fe deficient animals are likely to require many inseminations per conception and may rarely abort (Kumar et al., 2011a). Typically, Fe deficiency has characteristic clinical signs such as anaemia, low weight gain, repeat breeding, reduced feed intake and pica (Pietzak, 2014).

Iodine

I is an essential micronutrient in cattle reproduction. Generally, I is found in the diet as iodide and is required for thyroid hormone synthesis (Kumar et al., 2011b). Reproductive insufficiency can result from inadequate levels of I in the thyroid gland, causing decreases in conception rates and impaired ovarian function (Balamurugan et al., 2017). It is also involved in the brain development of progeny as well as growth and foetal development (Velladurai et al., 2016).

A deficiency of I can lead to failure of fertilization, early embryonic death, stillbirth with weak calves, abortion, delayed puberty, irregular oestrus cycles, and retained placenta in cows/heifers, whereas a decrease in libido and deterioration of semen quality may occur in males (Balamurugan et al., 2017). Goitre (thyroid gland enlargement) is also seen especially in young animals, as well as increased perinatal mortality and impaired reproduction (Grace and Waghorn, 2005). Increased I intake has been linked to several health problems including suppressed oestrus (standing heat), extended gestation periods, and decreased resistance to infection and disease (Balamurugan et al., 2017; Franke et al., 2009).

Serum metabolites in animal reproduction

Cholesterol

CHOL is a structured fat or lipid circulating in the bloodstream, which is present in all body cells and necessary for life maintenance (Damptey et al., 2014). CHOL gives the structural framework for essential metabolic processes including the production of steroid hormones; it influences the synthesis of bile acids necessary for breaking down fats and it also promotes embryonic growth and supports cell membrane formation (Guzel and Tanriverdi, 2014). CHOL level in cows tends to increase as a result of high-energy feed intake and it is a good indicator of decreased growth performance and lack of energy (Utama et al., 2018).

High CHOL concentrations are also indicators of biliary or hepatic diseases, insufficient thyroid hormone production, Cushing disease, and high-fat meal intake (Kahn and Line, 2010). Increased CHOL levels raise the probability of reproductive disorders (irregular cycles or suboestrus, repeat breeding, and endometritis), diabetes mellitus, and cardiovascular diseases in obese cows (Kumar, 2014). Increased risk of retained placenta in cows can be associated with lower prepartum concentrations of CHOL. Furthermore, low serum CHOL is a good indicator of energy deficit during early lactation and a better predictor of postpartum diseases (Sepúlveda-Varas et al., 2015).

CHOL level is typically high in multiparous cows and gradually increases after calving due to body fat metabolism (Saqib et al., 2018). CHOL is also known for its influence on ovarian steroid hormones’ synthesis (Jeong et al., 2015). CHOL is a precursor for the manufacture of steroid hormones, which are well known for their reproductive effects (Oguro, 2019). Estrogens and androgens are the most recognized sex steroid hormones, while progestogens represent a third type of sex steroid hormones (Miller and Auchus, 2011). Each of these sex steroid hormones is made from CHOL. Progesterone (PRG) is made from CHOL in the corpus luteum (CL) of the ovary during early pregnancy, and PRG synthesis continues in the placenta of mammals (Oguro, 2019).

Total protein

A study by Damptey et al. (2014) indicated that TP status in cows can be determined by monitoring BUN, globulin, and ALB. There are significant differences observed in different breed types and the concentrations of TP (Kalyani et al., 2018). Significantly higher concentrations of TP in cyclic cows (9.19 ± 0.45 g/dl) may be seen as a result of environmental effects, nutritional imbalances, and breed differences (Ahmad et al., 2004). TP concentration is a good indicator of liver and kidney damage (García et al., 2017). Cows/heifers with inflammation of the endometrium may also show elevated concentrations of TP (19.16 ± 1.00 g/dl), which may lead to reduced fertility (Ahmad et al., 2004). The normal range of TP in cows is 6.7–7.5 g/dl (Julie et al., 2021).

Based on the direct proportion of TP and serum globulin, TP concentrations have been associated with an increase in parity because older cows have a more developed immune system and have been exposed to pathogens (Bobbo et al., 2017). In older cows, increased protein intake can cause impaired fertility and also lead to an increase in services per conception (Ahmad et al., 2004). The TP concentration in gravid cows tends to increase approximately 8 weeks before calving and rapidly decreases at calving (Žvorc et al., 2000). The colostrum loss of globulin can cause the concentration of TP to be reduced during parturition (Bobbo et al., 2017).

Urea nitrogen/BUN

In mammals, urea nitrogen/BUN is a naturally occurring product of metabolism, which is endogenously produced by amino acid and protein catabolism in living organisms (Tshuma et al., 2014). Urea formation mainly takes place through typical nitrogen excretion by the liver. The microorganisms in the rumen and reticulum convert urea into protein (Kertz, 2010). Embryo growth and implantation can be negatively affected by way of excessive urea tiers, which minimize the pH in the uterus (Tshuma et al., 2014). Urea’s reaction with water becomes an organic hazard as it actively degrades to ammonia and this urea toxicity is commonly seen in ruminants (Raidal and Jaensch, 2006). Life-threatening spasms, forced rapid breathing, muscle twitching, vicious struggling, abdominal pain, bloat, frothy salivation, bellowing, and frequent urination may be seen in ruminants with urea poisoning (Shaikat et al., 2013). Furthermore, Shaikat and colleagues reported that animals are commonly found dead nearby the urea supplement source.

BUN is a useful indicator in the technique of metabolism of protein and the functioning of the kidney (Damptey et al., 2014). High urea concentration is related to renal disease, urinary obstruction, congestive coronary heart sickness, and gastrointestinal disorders (Kahn and Line, 2010). Elevated urea stage decreases Ca required to limit contraction efficiency (Ok et al., 2005). The role of Ca in ensuring easy parturition and uterine atony during placental detachment can link urea to difficulty in giving birth and placental retention in female bovines (Warnakulasooriya et al., 2018).

A study by Jeong et al. (2015) determined that there was no correlation between the stage of urea and cyclic resumption. However, previous research has shown diminished urea attention in non-cyclic cows for 2–6 weeks postpartum (Kalyani et al., 2018). Urea levels higher than 6.7 mmol/l have been reported to be detrimental to fertility in dairy cows (Butler et al., 1996; Sulieman et al., 2017). A decline in urea levels may be connected to low liver ureagenesis and low dietary protein intake (Macrae et al., 2006).

Creatinine

Cr is a macro-molecular metabolite produced from creatine and phosphocreatine; additionally, Cr is inherently found in muscles (Tesfaye et al., 2009). In clinical practice today, serum Cr is used as a biomarker for detecting and assessing severe and chronic renal disorders (Thomas et al., 2017). The degree of Cr release typically relies on the weight of the body muscle since it is produced from the muscle Cr phosphatase breakdown (Kalyani et al., 2018). A previous study has also associated the concentration of Cr with live body weight (Whittet et al., 2004). Creatinine is a product of metabolism; its excretion is associated to muscle mass (body weight) and Cr output can be used to estimate its excretion in grazing heifers and cows (Swartz et al., 2016; Brunsvig et al., 2017).

Alterations in serum Cr in the body can occur due to malnutrition, age, gender, post-surgical states, and movement (Tesfaye et al., 2009). Myopathological differences have also been associated with the lowered change in muscle tension and irregular Ca control (Wyss and Kaddurah-Daouk, 2000). Cr actively participates in tissue energy metabolism (Tesfaye et al., 2009). In agreement with this idea, some investigational outcomes have shown that there is an association between the disturbance of Cr concentration and muscular diseases (Wyss and Kaddurah-Daouk, 2000). A South African study found significantly lower Cr concentrations in Nguni cattle than in crossbred cattle (Mapiye et al., 2010). The value for the normal range of Cr in cows is 1–2 mg/dl in exotic cattle (Kalyani et al., 2018).

Research has shown that creatine improves functional performance in cases of muscular diseases and elevated levels of Cr are also known to improve muscle function (Kley et al., 2013). Reproductive processes require sufficient energy and proper muscular functions, and the role of Cr in energy metabolism as well as in Ca control connects Cr levels to energy deficits and muscular diseases in female bovines. Moreover, the oocyte requires large amounts of energy during its development in preparation for fertilization, and creatine metabolism in uterine tissues appears to correlate with phases of increased uterine energy demand throughout the female reproductive cycle, pregnancy, and parturition (Warzych and Lipinska, 2020). The specialized somatic cells that surround a mammalian egg have been shown to have creatine metabolism, and these cells work together to help egg maturation, fertilization, and embryo development (Muccini et al., 2021).

Globulin

In gravid cows, plasma globulin concentration decreases as a result of the γ-globulins from blood being transferred to the colostrum (Bobbo et al., 2017). The concentrations of globulin differ significantly among various cattle breeds (Kalyani et al., 2018). The concentration of globulin rises until the eighth month of gestation, followed by an increase caused by mammary gland immunoglobulin concentration, and an abrupt decrease is seen prior to calving (Žvorc et al., 2000). In cases of inflammation, globulin concentration tends to increase (García et al., 2017). Variations in serum globulin concentration have been used as a biomarker for immune response indications in animals (Bobbo et al., 2017). Studies have also linked endometritis in post-partum cows with low levels of globulin, and significantly associated mastitis with high globulin levels (Burke et al., 2010; Tothova et al., 2017).

Albumin

The measurements of ALB serve as an indicator of liver and kidney function as well as functioning as a useful tool in the assessment of the nutritional status of cows (Irfan et al., 2014). Low ALB concentration is significantly different in non-cyclic cows as compared to ALB in cyclic cows (Obese et al., 2015). Due to a lack of energy, a decrease in ALB levels may result from excessive ALB catabolism (Jeong et al., 2015). ALB has been reported to be low in repeat-breeding cows (Tombuku et al., 2017). The reduced blood ALB concentration is known to influence libido, causing a lack of oestrus, early embryo mortality, and uterine wall absorption of deceased embryos (Bearden et al., 2004). Early cycling cows display high ALB concentrations all through the peripartum period compared to the cows with postponed reproductive cyclicity (Krause et al., 2014).

In pregnant cows, a decrease in ALB concentration (below the normal range: 0.3–35.5 g/l) is usually followed by an elevation in globulin concentration (above the normal range: 7.5–8.8 g/l), also the ALB levels may decrease in mid-gestation and rise to normal levels until calving (Žvorc et al., 2000). The concentration of ALB in cows is prone to rise in cases of acute infectious diseases (Ahmad et al., 2004). The low ALB concentration is related to hepatic failure due to inflammation (García et al., 2017).

During early lactation, a significantly low concentration of ALB may occur due to fatty liver disorder, and an increase in ALB may be noted from about 15 up to 90 days post-calving (Bobbo et al., 2017). Downer cows may have normal Ca levels due to low ALB concentration, which could lead to a misleading diagnosis (Seifi et al., 2005). Because ALB binds to the majority of the total Ca in the body, before diagnosing hypocalcaemia, total Ca should always be adjusted for ALB levels. For every 1 g/dl (10 g/l) decline in serum albumin content, the blood total Ca concentration drops by about 0.8 mg/dl (0.25 mmol/l) (Goyal et al., 2021).

Hormones in animal reproduction

Estrogen

Estrogen is among many hormones produced by the ovaries. Additionally, estrogen is produced in the extra-gonadal regions of the body such as the mesenchymal cells of adipose tissue and skin, bone chondrocytes and osteoclasts, cells of the aortic smooth muscle, and vascular endothelium and also in numerous parts of the brain such as medial basal hypothalamus and anterior hypothalamus (Çiftci, 2013). Estradiol17β (E2), estrone (E1), and estriol (E3) are the three main forms of estrogen naturally produced in an animal body (Çiftci, 2013). The pro-reproductive mediation of estradiol (the predominant form of estrogen) occurs in various organs and is paramount for several biological processes (Schulster et al., 2016).

The mode of action for estradiol is to bind estrogen receptors activating the production of autocrine and paracrine factors (growth factors and cytokines such as transforming growth factor β, leukaemia inhibitory factor, endothelin-1, and nitric oxide) facilitating reproductive processes, influencing growth (stimulate the secretion of growth hormone), maturation, reproductive tract function, sexual differentiation, and sexual behaviour (Çiftci, 2013; Rosselli and Dubey, 2006). Furthermore, estradiol plays an important role in the regulation of many physiological processes that are essential for the establishment of pregnancy in cows/heifers and has direct and/or indirect action on the uterus (Ciernia et al., 2021; Pohler et al., 2012). Research has also related embryo survival and pregnancy establishment in beef cows with estradiol levels prior to ovulation (Northrop et al., 2018).

A recent study that looked at the influence of estradiol prior to ovulation and PRG after ovulation on the proportion of pregnant beef cows after embryo transfer found that the concentration of estradiol after embryo transfer had a beneficial effect on the proportion of pregnant cows (Ciernia et al., 2021). Research has also shown that embryo losses appeared to occur after maternal recognition of pregnancy, indicating that the increase in estradiol before ovulation may have effects on early placentation processes (Madsen et al., 2015).

Progesterone

PRG is a significant controller of numerous reproductive processes, for instance, ovulation, menstrual cycle, implantation, and maintenance of pregnancy in mammals (De Amicis et al., 2012). In different animal species and humans, PRG is a sexual hormone that participates in the reproduction of both females and males (Valadez-Cosmes et al., 2016). PRG is a steroid hormone mainly synthesized and secreted by ovaries, placenta, adrenal glands, and testis (Blavy et al., 2016). It has a known characteristic of maintaining pregnancy in female bovines (Stevenson and Lamb, 2016). In females, the 4-pregnene-3,20-dione (PRG) has an important role in the reproductive cycle regulation in mammals (Yu and Maeda, 2017).

PRG is vital for the development and upkeep of pregnancy and performs an important role in regulating endometrial secretions important for stimulating and mediating modifications in conceptus growth and differentiation all through early pregnancy in ruminants (Lonergan et al., 2015; Yan et al., 2018). Conception failure, higher pregnancy loss, or embryo death has been associated with low PRG levels in dairy cows (García et al., 2017; Kanazawa et al., 2022; Martins et al., 2022).

The global occurrence of preterm births is up to 5–18% and they are connected to calf mortalities and morbidity (Minguet-Romero et al., 2014). To avoid pre-term labour, PRG treatment is mostly used to improve management in reproduction (Romero et al., 2014). At the beginning of the luteal phase, low levels of PRG (<0.2 ng/ml) have negative impacts on embryo survival due to its influence on the interval to first ovulation, conception rate, oocyte development, and embryo quality, which are known to be directly linked to the negative energy balance in the post-partum period (Martin et al., 2013).

Measures of PRG levels in cows have been used to evaluate the reproductive status for pregnancy diagnosis to improve fertility (Blavy et al., 2016). There have been developments (ELISA Assay Kit) in technologies that can be used for PRG measurements on farms. To establish normality in the assessment of PRG levels, the consideration of different reproductive cycle stages (e.g., luteal phase and follicular phase) is essential for pre-conversion to obtain proper measurement interpretation (Gorzecka et al., 2011). PRG can be measured from blood, faeces, saliva, and milk (ideal in dairy industries) (Molefe and Mwanza, 2020a; Yu and Maeda, 2017). A high concentration of PRG is sustained during gestation and it is the best biomarker for the evaluation of reproductive status (Valadez-Cosmes et al., 2016).

Prostaglandins

Prostaglandins are a group of biological lipid complexes that have diverse hormone-like effects in animals (Dudhatra et al., 2012). These hormones are also described as autacoids and are known to be present in every tissue in both humans and animals (Katiyar et al., 2016). According to structure and function, prostaglandins A, B, E, and F are the four groups of prostaglandins, of which only F (PGF2α) and E directly affect fertility and the reproductive system (Tsai et al., 2001). In cows, prostaglandin F2a (PGF2α) synthesized in the uterus can be stimulated by oxytocin (OT) in the tissue of the endometrium and result in degradation of the CL and recurring oestrus (Kubo et al., 2018). The use of prostaglandins (PGF2α) in pregnant cows has been to prompt uterine contraction and elevate phagocytosis inside the uterus (Younger et al., 2014).

Prostaglandins have other functional properties of stimulating contractions of the myometrium in cattle (Sauls et al., 2018). In nearly all mammals, prostaglandins are recognized for their function in local luteal regulation as well as a means to advance breeding proficiency and as a treatment for retained placenta, pyometra, anoestrus, as well as endometritis (Dudhatra et al., 2012). Natural uterine clearance of bacterial infections (Fusobacterium necrophorum, Trueperella pyogenes, Arcanobacterium pyogenes, and Escherichia coli) occurs in cows, only about 20% of the infections may last for up to 3 weeks after calving (Masoumi et al., 2018; Younger et al., 2014). Due to prostaglandin’s ability to induce uterine contraction leading to foetal expulsion (ecbolic properties), it is also useful in the elimination of intraluminal uterine substances and luteolysis (Rigby et al., 2001).

Low breeding capacity, anoestrus, infertility, and sub-fertility may as well successively occur as a result of deferred uterine clearance (Younger et al., 2014). Termination of pregnancy can also be executed by the use of PGF2α and its analogs as they can suppress the peripheral levels of PRG by inducing luteal regression, prompting abdominal contraction, and causing part of the cervix to relax (Katiyar et al., 2016). Because the CL actively releases the PRG hormone, which inhibits oestrus, the luteal phase in cows is ideal for synchronizing oestrus with the injection of the prostaglandin hormone (PGF2) (Mukkun et al., 2021). By infusing the PGF2 hormone, the CL is lysed, and the PRG hormone is reduced (Wenzinger and Bleul, 2012). Prostaglandins are used to induce abortion in the first 5 months of pregnancy (150 days) and have also been proven to trigger calving as early as 255 days (Dudhatra et al., 2012).

Oxytocin

OT is a nonapeptide posterior pituitary hormone secreted through the paraventricular nuclei and supraoptic nuclei of the hypothalamus, which is also deposited into the bloodstream by the posterior pituitary neurons (Uvnäs-Moberg et al., 2001). The increase of Ca (Ca²⁺) in the cells results from OT receptors that trigger contractions of the uterus and play a role in both parturition and lactation processes in animals (Arrowsmith and Wray, 2014). In mammals, the secretion of OT is through the corpora lutea (Stormshak, 2003). OT is known to positively influence uterine contractility such as when used in instances of forcefully causing uterine contractions after labour to discontinue postpartum haemorrhages by compressing the blood vessels of the uterus (Heppelmann et al., 2018).

In the induction of labour, OT can be useful and is most ideal when the advantages for foetal expulsion before normal delivery exceed the danger associated with the maintenance of pregnancy (Arrowsmith and Wray, 2014). Characteristic functions of OT include induction of uterine contraction, uterine involution, uterine motility, calving, and the expulsion of uterine contaminants and stimulation of prostaglandins (PGF2α) synthesis (Palomares et al., 2010). Both neurogenic OT and circulatory OT play a part in the coordination processes such as foetal–mother attachments and other parental connections (Uvnäs-Moberg et al., 2001). OT has also been used in contraction activation of the myometrium in health management problems and preterm labour (Arrowsmith and Wray, 2014).

In dystocia management, OT is commonly used to correct the disorder although it is only known to succeed in about 50% of the cases (Arrowsmith and Wray, 2014). When 8 h have passed while the animal is still in the first stage of labour, OT can be given as intervention (Regmi and Gautam, 2020). Infusion of oxytocin causes hyperactivity of the uterus, of which the placenta–foetal unit is unable to recompense, this subsequently leads to reduced oxygen supply and blood flow to the foetus causing distress or foetal-hypoxia, tetanic contractions, and ultimately foetal death (Liston et al., 2002). Following the releasing hormone from the pituitary gland, the maternal circulatory increase of oxytocin concentration is usually seen at the onset of parturition in mammals (Blanks and Thornton, 2003). Additionally, the ejection of oxytocin in animals has been reported to be rhythmic for the period of foetal expulsion (Arrowsmith and Wray, 2014). The inconsistency in oxytocin’s role during labour indicates a greater need to further study its role during parturition.

Conclusion

In domestic livestock, sufficient measures of minerals in their naturally dynamic structures are basically needed for ideal production and reproduction. The equilibrium in metabolic markers is urgent to the proper working of the reproductive system and vital for further developed reproduction status in limited livestock agriculture. The disregard for hazards identified with mineral and hormonally unbalanced characteristics can turn around both hormonal and mineral advantages in bovine production. In cows, serum metabolites can be used to predict peripartum diseases, productivity, and reproductive function. Hormonal balance is becoming an increasingly essential component in lowering foetal and cow mortality, as well as the incidence of reproductive diseases that have unfavourable economic consequences in livestock farming. Female cattle reproductive ability is highly influenced by mineral and hormonal balance in producing animals. In terms of farm management and optimizing reproductive output, mineral requirements and reproductive hormones in livestock farming should be taken into consideration. The effective operation of the reproductive system and increased output status in farming require a balance of metabolic parameters.