The antioxidant micronutrients refers to minerals (zinc, selenium and copper) and vitamins (A, C and E)
(Adjepong et al., 2016; Opara and Rockway 2006;
Mohammed et al., 2024 a,b). The progresses in antioxidant micronutrient functions has made over the past decades for the purposes of increasing reproductive performance or treatment of dysfunction (
Bouayed and Bohn 2010;
Senosy et al., 2017, 2019;
Vašková et al., 2023). The antioxidant micronutrients have pivotal roles for protecting body function from damage caused by free radicals
(Gasselin et al., 2020; Rathor et al., 2023). Therefore, their supplementation to live mammalian species or in vitro culture media might improve ovarian follicle development, oocyte maturation and the further embryo and live birth development (
Kassab and Mohammed 2014a,
b) (Fig 1).
Antioxidant micronutrients improve reproductive performances through the significant increases in reproductive hormones values, sizes and numbers of ovarian follicles in addition to increases of ovulation rates and corpora lutea development
(Mumford et al., 2016; Senosy et al., 2017, 2019;
Chen et al., 2023). In addition, antioxidant micronutrients supplementation to maturation media of oocytes promotes maturation and the subsequent embryo development
(Yao et al., 2023). The antioxidant micronutrients improved embryos’ quality and stimulated their mitochondrial function (
Gomes da Silva et al., 2023). Hence, this article is designed to discuss the potential impact of antioxidant micronutrient supplementation on development of ovarian follicle, maturation of oocytes, development of embryos, pregnancy and live birth.
The current article was designed according to the procedure approved by Scientific Research Deanship, King Faisal University, Saudi Arabi from October to April 2024 (GrantA057). The data were obtained from web of science databases.
Ovarian follicle development
Ovarian structures’ development is a complex process that involves the growth and maturation of ovarian follicles. At birth, ruminant species have about 1-2 million follicles in their ovaries. However, only a few hundred of these follicles will ever develop into mature oocytes and be released over ovulation. The development of ovarian follicles is stimulated by follicle stimulating hormone and luteinizing hormone. The stages of ovarian follicles include primordial follicle, primary follicle, secondary follicle, graafian follicle and corpora lutea (
Gordon 2003;
Mohammed et al., 2022; 2024c,
d). Ovarian follicle development is a critical process for successful of reproduction (Fig 2). It allows the females to produce oocytes that can be fertilized and develop into live births. The higher sizes of ovarian follicles the higher developmental competence of the resulting oocytes and embryos
(Al-Zeidi et al., 2022a,b; Aljubran et al., 2023).
Antioxidant micronutrients improve reproductive performances through the increases in reproductive hormones’ values, sizes and numbers of ovarian follicles in addition to increase of ovulation rates and embryo development during oestrous or menstrual cycles
(Senosy et al., 2017, 2019;
Mohammed 2018;
Ali et al., 2021; Chen et al., 2023; Mohammed et al., 2024a,b). Antioxidant micronutrients (minerals and vitamins) protect the follicles from degeneration by free radicals. In addition, the higher levels of antioxidant micronutrients are more likely to ovulate ovarian follicles and promote the chance of pregnancy. Therefore, it is expected, upon ovarian transplantation (Fig 3), stimulation of ovarian follicle development due to antioxidant micronutrient supplementation.
It has been assumed that antioxidant micronutrients are unlikely to be toxic since they are often natural products. Over fifty percent of athletes consumed doses of antioxidant supplements higher than the recommended daily allowance. It is important to note that exogenous antioxidant supplements should not be taken in excessive amounts, which potential harms of supplementation with high doses had been indicated in athletes
(Li et al., 2022). The high dose harmful effects of antioxidant supplements in athletes include increased oxidative stress, increased plasma monoaldehyde levels and reduced mitochondrial biogenesis
(Bryant et al., 2003; Yfanti et al., 2012; Paulsen et al., 2014).
Oocyte quality and maturation
Oocyte quality could be determined through morphological and biochemical features
(Mohammed et al., 2005; Mohammed et al., 2024d). Oocyte morphology, or the physical appearance of an oocyte, is considered one of the most important factors in determining its quality. Good oocyte quality is essential for successful fertilization, embryo development and pregnancy. Oocyte quality is determined through morphological and biochemical features, which is essential for successful fertilization, embryo development and pregnancy. The morphological features include cumulus-enclosed cells, diameter, uniformity of zona pellucida, homogeneous and translucent cytoplasm, appropriate size polar body, perivitelline space and meiotic spindle (
Gordon 2003;
Mohammed et al., 2005, 2008,
2010,
2019) (Fig 4).
In addition, the biochemical features that have been associated with oocyte quality can be found in the follicular fluid, the cumulus cells and the oocyte. These features might include metabolites, reactive oxygen species, mitochondrial function, gene expression (
Gordon 2003,
Mohammed et al., 2019). Gomes da Silva et al., (2023) concluded that feeding trace mineral supplements in proteinate form and selenium-yeast to transition cows promote oocyte quality.
Oocyte maturation is a complex process that involves several key events including cytoplasmic and nuclear changes as germinal vesicle breakdown and progress to metaphase II stages (
Gordon 2003;
Mohammed et al., 2005; Hatirnaz et al., 2024) (Fig 5). Oocyte maturation is essential for successful fertilization, zygote formation and the subsequent embryonic development. It allows the oocyte to reduce its chromosome number through meiotic division, which is necessary for the formation of a diploid zygote after fertilization. The zygote then develops into an embryo, fetus and eventually a new individual.
The germinal vesicle nucleus is not visible in the cytoplasts of ruminants oocytes whereas is it visible in rodent, rabbit and human oocytes
(Mohammed et al., 2005, 2022). To visualize the GV nucleus in ruminant oocytes used in assisted reproductive techniques, ultracentrifugation at 15,000 rpm for 15 min is required. The time required for the oocyte to reach GVBD stage is 2-3 h of mouse oocytes and 5-6 h of ruminant and human oocytes as well. In addition, the time required for the oocyte to reach metaphase II stage is 15-17h of mouse oocytes and 24 h of ruminant and human oocytes (
Gordon 2003;
Mohammed et al., 2005).
Concerning to antioxidants effects,
Yao et al., (2023) concluded that zinc supplementation enhances ovine oocyte maturation and the following embryo development.
Lai et al., (2023) showed that zinc deficiency compromises the maturational competence of porcine oocyte through apoptosis induction.
Tripathi et al., (2023) showed that antioxidants in matured oocytes caused alterations in mRNA related gene expression of growth, stress and apoptosis. They reduced oxidative stress in oocytes by decreasing ROS levels, thus leading to improvement of embryo quality and quantity. Collectively, antioxidant micronutrients supplementation to
in vivo live organism or
in vitro culture media is indicated to promote oocyte maturation and resulting embryo development.
Embryo development
Antioxidant micronutrients are essential for several physiological processes in embryos of humans and animals
(Arhin et al., 2017). The improvement of oocyte maturation through antioxidant micronutrients is known to play a significant role in embryo developmental competence
(Yao et al., 2023). Improvement of cytoplasm maturation promotes developmental competence of embryos produced
(Mohammed et al., 2005; Córdova et al., 2010). Antioxidants improve the quality of embryos produced
in vitro.
Castillo-Martín et al., (2014) found enhancement of survival rate and redox status of
in vitro produced porcine blastocysts upon supplementing L-ascorbic acid. Additionally, zinc supplementation to vitrification medium improves oocyte maturation and fertilization
in vitro (Geravandi et al., 2017). Antioxidant micronutrients can protect embryo cells from damage caused by free radicals and can protect the embryo from oxidative stress. Supplementing oocytes and embryos with a combination of antioxidants improved the quality and quantity of embryos produced through protecting the embryo’s DNA from damage, reducing inflammation, improving blood flow to the uterus and supporting cell growth and development.
Fertility and reproduction
Antioxidant micronutrients are essential and played important roles in the normal growth and reproduction in animals and humans as well (
Hiten and Kurlak, 2015). They play pivotal roles in protecting sperms and oocytes from damage, improving hormonal production and supporting the development of the embryos and feti
(Al-Gubory et al., 2010). Vitamin C is essential for the production of collagen, which is important for the development of the placenta and uterus
(Lo et al., 2015). Vitamin E and zinc is important for hormonal production as testosterone and progesterone in addition to sperm development and function
(Jalali et al., 2020; Sánchez-Rubio et al., 2020;
Weiss, 2022). Selenium is well-known to support maximal expression of the selenoenzymes, sperm development and function
(Zhou et al., 2023; Zhu et al., 2023). Women supplementing during pregnancy vitamin C, vitamin E and beta-carotene had higher pregnancy rates (
Menard, 1997). In addition, supplementation of vitamin C, vitamin E, selenium and zinc before assisted reproductive technology had a higher sperm quality including sperm count and motility (
Majzoub and Agarwal 2018;
Khalil et al., 2019). Hence, supplementing the requirements of antioxidants is essential to maintain essential functions within the body, specially fertility and reproduction. On the other hand, insufficient stores or intake of antioxidant micronutrients can have adverse effects on the pregnancy and fetus development. Numerous studies implicate antioxidant micronutrients deficiency in several reproductive and obstetric complications including female and male infertility
(Mangione et al., 2023).
