How beta-carotene helps to improve the success rate of insemination in cows

Success at the first insemination is key to optimal reproductive performance in dairy cows. The fertility of lactating dairy cows has reportedly decreased over the last decades. In pasture-based systems, such as in Ireland and New Zealand, conception rates to the first insemination vary between 39 and 52%, while the rates in feedlot systems are as low as 30 to 40% [1]. A failed insemination may lead to an increase in calving interval, insemination numbers, reproductive treatment, feeding, culling, and replacement heifers. All of these lead to additional costs that can sum up to an average of 290 euros [2].

Consequently, lower fertility results reduce the profitability of dairy farming. However, fertility is a complex subject that depends on many factors such as breed, season, and diet. Determining the underlying biology of the dairy cow that contributes to poor fertility and coming up with methods to increase fertility, therefore, are two of the biggest difficulties facing reproductive biologists, nutritionists, and geneticists.

Nutrition is one of the essential factors in gestation, in which beta-carotene also plays an important role [3]. In this article, we focus on the effect of beta-carotene in the first stage of pregnancy: ovulation.

What is beta-carotene?

Beta-carotene is a provitamin for vitamin A. This means that beta-carotene is converted into vitamin A in the body, however, it also acts independently from vitamin A. It is found in green leafy vegetables (such as spinach), cabbages, carrots, mangoes, and tangerines and gives the characteristic orange color to some of these vegetables and fruits. In dairy farming, beta-carotene is mainly provided by forages.

For cattle, it is calculated that an average of 1 mg of beta-carotene is equivalent to 400 IU of vitamin A. A lactating cow needs up to 300 mg of beta-carotene per day [4].

What is the effect of beta-carotene on reproductive performance?

Beta-carotene is linked to numerous benefits such as skin health, lung health, eye health, better cognitive function, and even a reduction of the risk of certain cancers. Next to all these benefits, beta-carotene also serves as an antioxidant. And it is exactly this function, that helps improve fertility.

Low levels of beta-carotene and vitamin A result in extended duration of estrus, delayed ovulation, slower development of the yellow body, and an increase in the incidence of ovarian cysts. All this leads to low conception rates and more abortions in early pregnancy. Thus, reproductive performance in cattle improves with dietary supplementation of beta-carotene even when the diet is supplemented with vitamin A [5].

How beta-carotene influences ovulation

Transformation of beta-carotene into vitamin A

Beta-carotene is a precursor for vitamin A. It is transformed into vitamin A (retinol) in the developing tissues such as the placenta, yolk sac, and embryo [6]. In contrast to vitamin A, beta-carotene is not toxic even when consumed in higher amounts [7].

Intact beta-carotene can be taken up from the maternal circulation by the developing tissues. Then it can be split by the embryonic beta-carotene-15,15′-oxygenase (CMOI) to synthesize retinaldehyde for the embryo locally. Retinaldehyde is then transformed to vitamin A (retinol) by alcohol dehydrogenase (ADH) or retinol dehydrogenase (RDH) (see figure). Complete conversion of all of the ingested beta-carotene to vitamin A practically does not occur. About 17%–45% of the ingested beta-carotene is released in its intact form [6].

Maternal vitamin A plays a role in the development and/or maintenance of the placenta. Vitamin A is critical in the reproductive outcome of the cow, both at the time of insemination and throughout pregnancy. Deficiency can even lead to either a complete failure of reproduction prior to implantation or fetal resorption or malformation [8].

Antioxidant and oxidative stress

Beta-carotene has been found to have a beneficial contribution to the development of the ovaries and steroidogenesis [7]. Steroidogenesis is the process through which ovarian cells produce hormones, like progesterone, for the maintenance of reproductive tissues, regulation of ovarian function and ovulation, and establishment and maintenance of pregnancy [9]. Furthermore, beta-carotene is important for oocyte development [7]. An oocyte is an immature egg within a follicle. Typically only one oocyte develops in a mature egg, ready for ovulation and in a later stage, fertilization. The quality of the oocytes is thus of great importance. However, this quality is affected by a process known as oxidative stress. Oxidative stress is involved in the decline in oocyte quality.

In the body oxidative stress is induced by an excess of so-called reactive oxygen species (ROS). These ROS are unstable molecules called free radicals that contain oxygen. Free radicals can damage cells by stealing their electrons (in a process called oxidation) (see figure 2).

These free radicals can be neutralized by cellular antioxidants. When there is an increase in ROS and a decrease in antioxidants, oxidative stress is the result (see figure 2). But how does all of this affect fertility?

There is a balance required between ROS and antioxidants for the development of a competent oocyte (see figure 3). Suppression of ROS has negative consequences on oocyte development since ROS also regulates the micro-environment of the oocyte. However, a high level of ROS and a low level of antioxidants result in a reduced pregnancy outcome as well [7],[10].

ROS are produced primarily in the mitochondria as byproducts of metabolism. It is known mitochondria are abundant in fully-grown mammalian oocytes and play a functional role in fertilization and development. Excessive ROS disrupt the distribution of mitochondria and they damage the cellular proteins and DNA. Furthermore, excessive ROS has been suggested to inhibit cell maturation and even lead to cell death [7].

So what is the role of beta-carotene in this process? Beta-carotene is a strong antioxidant and completely neutralizes the free radicals, avoiding that the ROS can damage the cells of the cow (and in this case the cells of the oocytes). Thus, beta-carotene works as a free-radical remover: they donate an electron to the cell in the oocyte that lost an electron due to oxidation, effectively stopping the cell damage. Furthermore, beta-carotene not only reduces the ROS but it can even restore activity in the cell.

Fertitop bolus

Resco’s Fertitop is a bolus designed to prepare the cow for estrus and reproduction and consequently increase the success of insemination. The bolus slowly releases minerals, vitamins, and beta-carotene for 8 days. Fertitop releases a daily amount of 300 mg of beta-carotene. Fertitop has proven to increase the success of insemination. To read about the trials proving the efficacy of Fertitop, click here. To get access to the product page, please click here.      

Sources

[1] Williams, E. J., and A. C. O. Evans. “A Review of the Causes of Poor Fertility in High Milk Producing Dairy Cows.” Animal Reproduction Science, vol. 123, no. 3–4, Feb. 2011, pp. 127–38. https://doi.org/10.1016/j.anireprosci.2010.12.001.

[2] NADIS Animal Health Skills - Part 1 : What does poor fertility cost. (n.d.). Retrieved September 12, 2022, from https://www.nadis.org.uk/disease-a-z/cattle/fertility-in-dairy-herds-advanced/part-1-what-does-poor-fertility-cost/

[3] Lotthammer, K. (1979). Importance of beta-carotene for the fertility of dairy cattle. Feedstuffs, (51:16).

[4] de Jong, S. (1985). Rendabele rundveehouding (3rd ed.). Uitgeverij Terra.

[5] Hemken, R. W., & Bremel, D. H. (1982). Possible Role of Beta-Carotene in Improving Fertility in Dairy Cattle. Journal of Dairy Science, 65(7), 1069–1073. doi:10.3168/jds.S0022-0302(82)82314-X

[6] Shete, V., & Quadro, L. (2013, November 27). Mammalian metabolism of beta-carotene: Gaps in knowledge. Nutrients. MDPI AG. doi:10.3390/nu5124849

[7] Yu, S., Zhao, Y., Feng, Y., Zhang, H., Li, L., Shen, W., … Min, L. (2019). beta-carotene improves oocyte development and maturation under oxidative stress in vitro. In Vitro Cellular and Developmental Biology - Animal, 55(7), 548–558. doi:10.1007/s11626-019-00373-0

[8] Clagett-Dame, M., & Knutson, D. (2011). Vitamin A in Reproduction and Development. Nutrients, 3, 385–428. doi:10.3390/nu3040385

[9] Craig, Z. R. (2018). Plastic compounds. Encyclopedia of Reproduction, 707–713. doi:10.1016/B978-0-12-801238-3.64410-0

[10] Kala, M., Muhammad, |, Shaikh, V., & Nivsarkar, M. (2017). Equilibrium between anti-oxidants and reactive oxygen species: a requisite for oocyte development and maturation. Reprod Med Biol, 16, 28–35. doi:10.1002/rmb2.12013

[Figure 1] Shete, Varsha, and Loredana Quadro. 2013. “Mammalian Metabolism of β-Carotene: Gaps in Knowledge.” Nutrients. MDPI AG. https://doi.org/10.3390/nu5124849.

[Figure 2] “How Antioxidants Work. | Cell Membrane, Free Radicals, Laser Skin Care.” n.d. Accessed September 12, 2022. https://www.pinterest.com/pin/271060471293497534/.

[Figure 3] Kala, Manika, | Muhammad, Vaseem Shaikh, and Manish Nivsarkar. 2017. “Equilibrium between Anti-Oxidants and Reactive Oxygen Species: A Requisite for Oocyte Development and Maturation.” Reprod Med Biol 16: 28–35. https://doi.org/10.1002/rmb2.12013.