Calcium

Ca is an essential macronutrient required by the body (Harper, Reference Harper2017). It is needed in large amounts in both animals and humans (Martinez et al., Reference Martinez, Sinedino, Bisinotto, Daetz, Risco, Galvão, Thatcher and Santos2016). 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., Reference Trailokya, Srivastava, Bhole and Zalte2017). Nevertheless, a lesser percentage of Ca in the body outside the skeleton is found in the blood and is important for survival (Suttle, Reference Suttle2010). Its functional properties include muscle contraction, nerve conduction, blood clotting, and maintaining healthy bones (Trailokya et al., Reference Trailokya, Srivastava, Bhole and Zalte2017). 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, Reference Fridjayanti and Dilaga2019). 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., Reference Trailokya, Srivastava, Bhole and Zalte2017). 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., Reference Soetan, Olaiya and Oyewole2010).

Low blood Ca predisposes cows to peri-parturient disorders, such as mastitis and ketosis (Sepúlveda-Varas et al., Reference Sepúlveda-Varas, Weary, Noro and von Keyserlingk Ma2015). Reduced blood Ca concentrations are typically concurrent with increasing plasma Mg concentrations (Fikadu et al., Reference Fikadu, Tegegne, Abdela and Ahmed2016). 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., Reference Soetan, Olaiya and Oyewole2010).

Research has shown that high-parity Jersey cows are more prone to hypocalcaemia and heifers rarely experience milk fever (Roche and Berry, Reference Roche and Berry2006). Moreover, Ca requirements change depending on animal age and production status (Mokolopi and Beighle, Reference Mokolopi and Beighle2006). Jersey breeds are high-producing cows and widely selected due to their high milk fat content (Chiwome et al., Reference Chiwome, Kandiwa, Mushonga, Sajeni and Habarugira2017). 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 Reference Krehbiel2014). 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., Reference Chiwome, Kandiwa, Mushonga, Sajeni and Habarugira2017). Therefore, higher milk yields are associated with a higher risk of developing metabolic disorders. In an epidemiological study by Lean et al. (Reference Lean, DeGaris, McNeil and Block2006), 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., Reference Chiwome, Kandiwa, Mushonga, Sajeni and Habarugira2017).

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., Reference Trailokya, Srivastava, Bhole and Zalte2017). A sufficient Ca supply can greatly boost reproductive output and body weight providing better oestrous physiological conditions for grazing bovines (Zhou et al., Reference Zhou, Zhang, Xue, Yue, Yang and Xue2021).

Magnesium

Mg is the second most abundant intracellular divalent cation (Blaine et al., Reference Blaine, Chonchol and Levi2014). Several enzymes rely mainly on intracellular Mg for the regulation of their metabolism (Mahon et al., Reference Mahon, Belloc, Lagarde, Chollet, Moreau-Gaudry, Reiffers, Goldman and Melo2003). Nerve transmission is one of the most important functional characteristics of intracellular Mg (Wang et al., Reference Wang, Zhu, Liu, Gong and Li2017). 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., Reference Blaine, Chonchol and Levi2014). The second mechanism is characterized by Mg transport over the epithelium with no dependency on the potential differences (Martens and Schweigel, Reference Martens and Schweigel2000).

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., Reference Kronqvist, Emanuelson, Spörndly and Holtenius2011). Low concentrations of potassium prevent the uptake of Mg, while ammonia levels in the rumen stimulate Mg uptake (Blaine et al., Reference Blaine, Chonchol and Levi2014). Research has also shown that when Mg levels increase, there is a decline in plasma Ca concentrations during calving (Goff et al., Reference Goff, Kimura and Horst2002a), 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., Reference Musa, Lanyasunya and Mukisira2016). Other common observations of Mg deficits are that calves are born weak and deformed with enlarged joints and Arthrogryposis/contracture joints (Kreplin and Yaremcio, Reference Kreplin and Yaremcio2009).

Hypomagnesaemia is also known as grass tetany, winter tetany, and grass staggers depending on the conditions in which it may arise (Kronqvist et al., Reference Kronqvist, Emanuelson, Spörndly and Holtenius2011). The deficiency of Mg in the cerebrospinal fluid can lead to death as a result of hypomagnesaemia and tetany (McCoy et al., Reference McCoy, Hutchinson, Fitzpatrick, Rice and Kennedy2001). 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., Reference Velladurai, Selvaraju and Napolean2016).

Phosphorus

P is a vital nutrient required in all living organisms (Yang et al., Reference Yang, Huang, Kuo and Chiou2017). P is frequently stated as a ‘fertility’ mineral (Fageria et al., Reference Fageria, He and Baligar2017). 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., Reference Velladurai, Selvaraju and Napolean2016). 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, Reference Abrams and Atkinson2003). 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., Reference Yang, Huang, Kuo and Chiou2017).

P deficiency has been linked with clinical manifestations such as osteomalacia and stiffness (Bakunzi et al., Reference Bakunzi, Motsei, Nyirenda, Ndou, Dzoma and Mwanza2012). 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., Reference Takedani, Notsu and Koike2021). 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, Reference Ateba and Beighle2011). 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, Reference Ateba and Beighle2011). 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., Reference Atli, Bender, Mehta, Bastos, Luo, Vezina and Wiltbank2012). Detrimental effects associated with Se insufficiency in animals include low growth, poor health, and low fertility (Glombowsky et al., Reference Glombowsky, Soldá, Campigotto, Volpato, Galli, Fávero, Bottari, Schetinger, Morsch, Baldissera, Machado and da Silva AS2017). Embryonic death during the first month of pregnancy, retained placentas, mastitis, metritis, and low fertility have been reported in cattle with Se deficiency (Bohrer, Reference Bohrer2017; Juárez et al., Reference Juárez, Lam, Bohrer, Dugan, Vahmani, Aalhus, Juárez, López-Campos, Prieto and Segura2021; Pereira and Vicente, Reference Pereira and Vicente2013). 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., Reference Al-Shaar, Satija, Wang, Rimm, Smith-Warner, Stampfer, Hu and Willett2020; Garam et al., Reference Garam, Hannah, Gitanjali, Dahyun and Min-Jeong2020).

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., Reference Balamurugan, Ramamoorthy, Mandal, Keerthana, Gopalakrishnan, Kavya, Kharayat and Katiyar2017; Omeje, Reference Omeje2016). Another study has associated Se insufficiency in cows and heifers with infertility and low disease resistance (Kreplin and Yaremcio, Reference Kreplin and Yaremcio2009). 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., Reference Balamurugan, Ramamoorthy, Mandal, Keerthana, Gopalakrishnan, Kavya, Kharayat and Katiyar2017; Mee, Reference Mee2004). Se supplementation also prevents oxidative stress from damaging cells and their membranes (Karaağaç et al., Reference Karaağaç, Pınarlı and Tarlak2022). Additionally, Se supplements have been indicated to improve the quality of milk (Safonov, Reference Safonov2022)

Copper

Cu is an important micronutrient required for the normal functioning of body metabolism in animals (Xinhuan et al., Reference Xinhuan, Chuchu, Shi, Cheng, Gang, Yunlong and Ling2017). Cu is known to influence reproductive performance, production, and growth in cows (Balamurugan et al., Reference Balamurugan, Ramamoorthy, Mandal, Keerthana, Gopalakrishnan, Kavya, Kharayat and Katiyar2017). 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., Reference Balamurugan, Ramamoorthy, Mandal, Keerthana, Gopalakrishnan, Kavya, Kharayat and Katiyar2017). Cu insufficiency has the same influence on reproduction as other mineral deficits predisposing cows to poor fertility and delayed puberty (Suttle, Reference Suttle2010). 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, Reference Lata and Mondal2021).

Additional indicators of low Cu concentration include increased incidences of retained placenta and repeat breeding (Kreplin and Yaremcio, Reference Kreplin and Yaremcio2009). 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., Reference Balamurugan, Ramamoorthy, Mandal, Keerthana, Gopalakrishnan, Kavya, Kharayat and Katiyar2017). 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, Reference Suttle2010).

Iron

Fe is required in every animal for maintaining natural processes, for example, oxygen transportation and electron transfer of enzymes (Sánchez et al., Reference Sánchez, Sabio, Gálvez, Capdevila and Dominguez‐Vera2017). 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, Reference Molefe2016).

Fe distribution in foetal development is cell-mediated by the extraembryonic visceral endoderm and syncytiotrophoblast in the placenta (Lieu et al., Reference Lieu, Heiskala, Peterson and Yang2001). 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., Reference Andrews, Matin, Bahrami, Damjanov, Gokhale and Draper2005). Fe deficient animals are likely to require many inseminations per conception and may rarely abort (Kumar et al., Reference Kumar, Kawai and Akira2011a). Typically, Fe deficiency has characteristic clinical signs such as anaemia, low weight gain, repeat breeding, reduced feed intake and pica (Pietzak, Reference Pietzak, Davi and Gerard2014).

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., Reference Kumar, Pandey, AbdulRazzaque and Dwivedi2011b). 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., Reference Balamurugan, Ramamoorthy, Mandal, Keerthana, Gopalakrishnan, Kavya, Kharayat and Katiyar2017). It is also involved in the brain development of progeny as well as growth and foetal development (Velladurai et al., Reference Velladurai, Selvaraju and Napolean2016).

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., Reference Balamurugan, Ramamoorthy, Mandal, Keerthana, Gopalakrishnan, Kavya, Kharayat and Katiyar2017). Goitre (thyroid gland enlargement) is also seen especially in young animals, as well as increased perinatal mortality and impaired reproduction (Grace and Waghorn, Reference Grace and Waghorn2005). 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., Reference Balamurugan, Ramamoorthy, Mandal, Keerthana, Gopalakrishnan, Kavya, Kharayat and Katiyar2017; Franke et al., Reference Franke, Meyer, Wagner, Hoppen and Flachowsky2009).

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., Reference Damptey, Obese, Aboagye, Ayim-Akonor and Ayizanga2014). 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, Reference Guzel and Tanriverdi2014). 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., Reference Utama, Lee, Baek, Chung, Chung, Kim, Kim and Lee2018).

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, Reference Kahn and Line2010). 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, Reference Kumar2014). 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., Reference Sepúlveda-Varas, Weary, Noro and von Keyserlingk Ma2015).

CHOL level is typically high in multiparous cows and gradually increases after calving due to body fat metabolism (Saqib et al., Reference Saqib, Qureshi and Khan2018). CHOL is also known for its influence on ovarian steroid hormones’ synthesis (Jeong et al., Reference Jeong, Choi, Kang, Hur, Jung and Kim2015). CHOL is a precursor for the manufacture of steroid hormones, which are well known for their reproductive effects (Oguro, Reference Oguro2019). Estrogens and androgens are the most recognized sex steroid hormones, while progestogens represent a third type of sex steroid hormones (Miller and Auchus, Reference Miller and Auchus2011). 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, Reference Oguro2019).

Total protein

A study by Damptey et al. (Reference Damptey, Obese, Aboagye, Ayim-Akonor and Ayizanga2014) 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., Reference Kalyani, Aswani, Haritha, Srinivas and Kanaka2018). 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., Reference Ahmad, Lodhi, Qureshi and Younis2004). TP concentration is a good indicator of liver and kidney damage (García et al., Reference García, Prado, Galicia and Borderas2017). 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., Reference Ahmad, Lodhi, Qureshi and Younis2004). The normal range of TP in cows is 6.7–7.5 g/dl (Julie et al., Reference Julie, Subapriya and Vairamuthu2021).

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., Reference Bobbo, Fiore, Gianesella, Morgante, Gallo, Ruegg, Bittante and Cecchinato2017). In older cows, increased protein intake can cause impaired fertility and also lead to an increase in services per conception (Ahmad et al., Reference Ahmad, Lodhi, Qureshi and Younis2004). The TP concentration in gravid cows tends to increase approximately 8 weeks before calving and rapidly decreases at calving (Žvorc et al., Reference Žvorc, Matijatko, Beer, Foršek, Bedrica and Kuĉer2000). The colostrum loss of globulin can cause the concentration of TP to be reduced during parturition (Bobbo et al., Reference Bobbo, Fiore, Gianesella, Morgante, Gallo, Ruegg, Bittante and Cecchinato2017).

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., Reference Tshuma, Holm, Fosgate and Lourens2014). Urea formation mainly takes place through typical nitrogen excretion by the liver. The microorganisms in the rumen and reticulum convert urea into protein (Kertz, Reference Kertz2010). Embryo growth and implantation can be negatively affected by way of excessive urea tiers, which minimize the pH in the uterus (Tshuma et al., Reference Tshuma, Holm, Fosgate and Lourens2014). 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, Reference Raidal and Jaensch2006). 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., Reference Shaikat, Hasan, Hasan, Khan, Haque, Islam and Hossain2013). 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., Reference Damptey, Obese, Aboagye, Ayim-Akonor and Ayizanga2014). High urea concentration is related to renal disease, urinary obstruction, congestive coronary heart sickness, and gastrointestinal disorders (Kahn and Line, Reference Kahn and Line2010). Elevated urea stage decreases Ca required to limit contraction efficiency (Ok et al., Reference Ok, Basnakian, Apostolov, Barri and Shah2005). 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., Reference Warnakulasooriya, Marth, McLeod, Hanlon and Krekeler2018).

A study by Jeong et al. (Reference Jeong, Choi, Kang, Hur, Jung and Kim2015) 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., Reference Kalyani, Aswani, Haritha, Srinivas and Kanaka2018). Urea levels higher than 6.7 mmol/l have been reported to be detrimental to fertility in dairy cows (Butler et al., Reference Butler, Calaman and Beam1996; Sulieman et al., Reference Sulieman, Makawi and Ibrahim2017). A decline in urea levels may be connected to low liver ureagenesis and low dietary protein intake (Macrae et al., Reference Macrae, Whitaker, Burrough, Dowell and Kelly2006).

Creatinine

Cr is a macro-molecular metabolite produced from creatine and phosphocreatine; additionally, Cr is inherently found in muscles (Tesfaye et al., Reference Tesfaye, Průša, Kolářová, Šimonek and Lischke2009). In clinical practice today, serum Cr is used as a biomarker for detecting and assessing severe and chronic renal disorders (Thomas et al., Reference Thomas, Zachariah, Elamin and Hashim2017). 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., Reference Kalyani, Aswani, Haritha, Srinivas and Kanaka2018). A previous study has also associated the concentration of Cr with live body weight (Whittet et al., Reference Whittet, Klopfenstein, Erickson, Loy and McDonald2004). 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., Reference Swartz, Brake, Grings, Nelson, Wright, Walker, Bloom and Perry2016; Brunsvig et al., Reference Brunsvig, Smart, Bailey, Wright, Grings and Brake2017).

Alterations in serum Cr in the body can occur due to malnutrition, age, gender, post-surgical states, and movement (Tesfaye et al., Reference Tesfaye, Průša, Kolářová, Šimonek and Lischke2009). Myopathological differences have also been associated with the lowered change in muscle tension and irregular Ca control (Wyss and Kaddurah-Daouk, Reference Wyss and Kaddurah-Daouk2000). Cr actively participates in tissue energy metabolism (Tesfaye et al., Reference Tesfaye, Průša, Kolářová, Šimonek and Lischke2009). 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, Reference Wyss and Kaddurah-Daouk2000). A South African study found significantly lower Cr concentrations in Nguni cattle than in crossbred cattle (Mapiye et al., Reference Mapiye, Chimonyo, Dzama and Marufu2010). The value for the normal range of Cr in cows is 1–2 mg/dl in exotic cattle (Kalyani et al., Reference Kalyani, Aswani, Haritha, Srinivas and Kanaka2018).

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., Reference Kley, Tarnopolsky and Vorgerd2013). 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, Reference Warzych and Lipinska2020). 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., Reference Muccini, Tran, de Guing, Philip, Della Gatta, Galinsky, Sherman, Kelleher, Berry MJ, Walker, Snow and Ellery2021).

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., Reference Bobbo, Fiore, Gianesella, Morgante, Gallo, Ruegg, Bittante and Cecchinato2017). The concentrations of globulin differ significantly among various cattle breeds (Kalyani et al., Reference Kalyani, Aswani, Haritha, Srinivas and Kanaka2018). 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., Reference Žvorc, Matijatko, Beer, Foršek, Bedrica and Kuĉer2000). In cases of inflammation, globulin concentration tends to increase (García et al., Reference García, Prado, Galicia and Borderas2017). Variations in serum globulin concentration have been used as a biomarker for immune response indications in animals (Bobbo et al., Reference Bobbo, Fiore, Gianesella, Morgante, Gallo, Ruegg, Bittante and Cecchinato2017). 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., Reference Burke, Meier, McDougall, Compton, Mitchell and Roche2010; Tothova et al., Reference Tothova, Mudroň and Nagy2017).

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., Reference Irfan, Esfandiari and Choliq2014). Low ALB concentration is significantly different in non-cyclic cows as compared to ALB in cyclic cows (Obese et al., Reference Obese, MacCarthy, Osei-Amponsah, Ayizanga and Damptey2015). Due to a lack of energy, a decrease in ALB levels may result from excessive ALB catabolism (Jeong et al., Reference Jeong, Choi, Kang, Hur, Jung and Kim2015). ALB has been reported to be low in repeat-breeding cows (Tombuku et al., Reference Tombuku, Widayati and Maharani2017). 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., Reference Bearden, Fuquay and Willard2004). Early cycling cows display high ALB concentrations all through the peripartum period compared to the cows with postponed reproductive cyclicity (Krause et al., Reference Krause, Pfeifer, Montagner, Weschenfelder, Schwegler, Lima, Xavier, Brauner, Schmitt, Del Pino, Martins, Corrêa and Schneider2014).

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., Reference Žvorc, Matijatko, Beer, Foršek, Bedrica and Kuĉer2000). The concentration of ALB in cows is prone to rise in cases of acute infectious diseases (Ahmad et al., Reference Ahmad, Lodhi, Qureshi and Younis2004). The low ALB concentration is related to hepatic failure due to inflammation (García et al., Reference García, Prado, Galicia and Borderas2017).

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., Reference Bobbo, Fiore, Gianesella, Morgante, Gallo, Ruegg, Bittante and Cecchinato2017). Downer cows may have normal Ca levels due to low ALB concentration, which could lead to a misleading diagnosis (Seifi et al., Reference Seifi, Mohri, Ehsani, Hosseini and Chamsaz2005). 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., Reference Goyal, Anastasopoulou, Ngu and Singh2021).

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, Reference Çiftci2013). Estradiol17β (E2), estrone (E1), and estriol (E3) are the three main forms of estrogen naturally produced in an animal body (Çiftci, Reference Çiftci2013). 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., Reference Schulster, Bernie and Ramasamy2016).

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, Reference Çiftci2013; Rosselli and Dubey, Reference Rosselli and Dubey2006). 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., Reference Ciernia, Perry, Smith, Rich, Northrop, Perkins, Green, Zezeski and Geary2021; Pohler et al., Reference Pohler, Geary, Atkins, Perry, Jinks and Smith2012). Research has also related embryo survival and pregnancy establishment in beef cows with estradiol levels prior to ovulation (Northrop et al., Reference Northrop, Rich, Cushman, McNeel, Soares, Brooks, Spencer and Perry2018).

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., Reference Ciernia, Perry, Smith, Rich, Northrop, Perkins, Green, Zezeski and Geary2021). 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., Reference Madsen, Perry, Mogck, Daly, MacNeil and Geary2015).

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., Reference De Amicis, Santoro, Guido, Sisci, Bruno, Carpino and Aquila2012). 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., Reference Valadez-Cosmes, Vázquez-Martínez, Cerbón and Camacho-Arroyo2016). PRG is a steroid hormone mainly synthesized and secreted by ovaries, placenta, adrenal glands, and testis (Blavy et al., Reference Blavy, Derks, Martin, Höglund and Friggens2016). It has a known characteristic of maintaining pregnancy in female bovines (Stevenson and Lamb, Reference Stevenson and Lamb2016). In females, the 4-pregnene-3,20-dione (PRG) has an important role in the reproductive cycle regulation in mammals (Yu and Maeda, Reference Yu and Maeda2017).

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., Reference Lonergan, Forde and Spencer2015; Yan et al., Reference Yan, Robinson, Shi and Mann2018). Conception failure, higher pregnancy loss, or embryo death has been associated with low PRG levels in dairy cows (García et al., Reference García, Prado, Galicia and Borderas2017; Kanazawa et al., Reference Kanazawa, Seki and Iga2022; Martins et al., Reference Martins, Sponchiado, Silva, Estrada-Cortes, Hansen, Penagaricano and Binelli2022).

The global occurrence of preterm births is up to 5–18% and they are connected to calf mortalities and morbidity (Minguet-Romero et al., Reference Minguet-Romero, Cruz-Cruz, Del, Ruíz-Rosas and Hern Andez-valencia2014). To avoid pre-term labour, PRG treatment is mostly used to improve management in reproduction (Romero et al., Reference Romero, Dey and Fisher2014). 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., Reference Martin, Friggens, Dupont, Salvetti, Freret, Rame, Gatien, Disenhaus and Blanc2013).

Measures of PRG levels in cows have been used to evaluate the reproductive status for pregnancy diagnosis to improve fertility (Blavy et al., Reference Blavy, Derks, Martin, Höglund and Friggens2016). 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., Reference Gorzecka, Codrea, Friggens and Callesen2011). PRG can be measured from blood, faeces, saliva, and milk (ideal in dairy industries) (Molefe and Mwanza, Reference Molefe and Mwanza2020a; Yu and Maeda, Reference Yu and Maeda2017). 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., Reference Valadez-Cosmes, Vázquez-Martínez, Cerbón and Camacho-Arroyo2016).

Prostaglandins

Prostaglandins are a group of biological lipid complexes that have diverse hormone-like effects in animals (Dudhatra et al., Reference Dudhatra, Mody, Patel, Modi, Chukewar, Kumar and Awale2012). These hormones are also described as autacoids and are known to be present in every tissue in both humans and animals (Katiyar et al., Reference Katiyar, Kharayat, Rautela, Chaudhary, Balamurugan, Kumar and Mishra2016). 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., Reference Tsai, Kot, Ginther and Wiltbank2001). 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., Reference Kubo, Iga, Fukuju, Kizaki, Osawa, Izaike and Takahashi2018). The use of prostaglandins (PGF2α) in pregnant cows has been to prompt uterine contraction and elevate phagocytosis inside the uterus (Younger et al., Reference Younger, Lulay and AR2014).

Prostaglandins have other functional properties of stimulating contractions of the myometrium in cattle (Sauls et al., Reference Sauls, Voelz, Mendonça and Stevenson2018). 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., Reference Dudhatra, Mody, Patel, Modi, Chukewar, Kumar and Awale2012). 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., Reference Masoumi, Badiei, Mousakhani, Dirandeh, Zhandi and Stear2018; Younger et al., Reference Younger, Lulay and AR2014). 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., Reference Rigby, Barhoumi and Burghardt2001).

Low breeding capacity, anoestrus, infertility, and sub-fertility may as well successively occur as a result of deferred uterine clearance (Younger et al., Reference Younger, Lulay and AR2014). 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., Reference Katiyar, Kharayat, Rautela, Chaudhary, Balamurugan, Kumar and Mishra2016). 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., Reference Mukkun, Yusuf, Toleng and Sonjaya2021). By infusing the PGF2 hormone, the CL is lysed, and the PRG hormone is reduced (Wenzinger and Bleul, Reference Wenzinger and Bleul2012). 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., Reference Dudhatra, Mody, Patel, Modi, Chukewar, Kumar and Awale2012).

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., Reference Uvnäs-Moberg, Johansson, Lupoli and Svennersten-Sjaunja2001). 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, Reference Arrowsmith and Wray2014). In mammals, the secretion of OT is through the corpora lutea (Stormshak, Reference Stormshak2003). 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., Reference Heppelmann, Volland, Pfarrer, Kietzmann, Bäumer, Merbach, Schoon, Wellnitz, Schmicke and Hoedemaker2018).

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, Reference Arrowsmith and Wray2014). 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., Reference Palomares, Gutiérrez, Portillo, Boscan, Montero, López, Maxwell, Carson and Soto2010). 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., Reference Uvnäs-Moberg, Johansson, Lupoli and Svennersten-Sjaunja2001). OT has also been used in contraction activation of the myometrium in health management problems and preterm labour (Arrowsmith and Wray, Reference Arrowsmith and Wray2014).

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, Reference Arrowsmith and Wray2014). 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, Reference Regmi and Gautam2020). 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., Reference Liston, Crane, Hughes, Kuling, MacKinnon, Milne, Richardson and Trepanier2002). 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, Reference Blanks and Thornton2003). Additionally, the ejection of oxytocin in animals has been reported to be rhythmic for the period of foetal expulsion (Arrowsmith and Wray, Reference Arrowsmith and Wray2014). The inconsistency in oxytocin’s role during labour indicates a greater need to further study its role during parturition.