Numerous factors have been identified as possible causes of SD and reproductive issues. For example, male infertility is caused by oxidative stress (OS) associated with environmental and lifestyle factors, including pollution, radiation, smoking and drugs, and systematic pathologies such as diabetes and cancer (Agarwal et al., 2018). In addition, the excessive amount of reactive oxygen species (ROS) can significantly damage the sperm antioxidant system, and sub-fertile and infertile males significantly have high ROS in the reproductive tract to impair reproductive cells (Martin-Hidalgo et al., 2019). Regarding female infertility, OS negatively affects fertility by causing reproductive cell membrane lipid peroxidation, cellular protein oxidation, and DNA damage (Smits et al., 2018; Noh et al., 2020).

Antioxidants can be a promising solution against OS since it plays a vital role to protect the reproductive system at the cellular response level against OS (Agarwal et al., 2018; Martin-Hidalgo et al., 2019; Noh et al., 2020). The intake of antioxidants can improve semen quality and prevent DNA damage (Lloyd and Hornsby, 2009; Moghadam et al., 2016; Martin-Hidalgo et al., 2019). For example, the polysaccharides such as antihypercholesterolemic found in sea cucumber, Holothurian nobilis could inhibit lipid peroxidation and improve the healing process of interstitial cells in hypercholesterolemia rats (Ulhusna et al., 2020). Saad et al. (2018) reported that the extract of sea cucumber, H. atra could protect testicular cytotoxicity and dysfunction induced by methotrexate in a rat model. Moghadam et al. (2016) suggested that the extracted saponin from sea cucumber H. leucospilota could enhance the maturation of pre-antral follicles in mice through limiting OS and TNF-α expression to induce antioxidant enzyme activity.

Intensive exercises can negatively impact the reproductive tissues in the rat by enhancing ROS generation, resulting in testicular spermatogenic and steroidogenic disorders. Oyster peptide supplement could significantly support the function of the hypothalamus-pituitary gonad axis in male rates during heavy load training. This supplement can considerably reduce OS in testis by up-regulating steroidogenic enzyme expression to promote steroidogenesis and spermatogenesis (Jin et al., 2021b). In another study, oyster peptides and oyster powder were used to feed rats with reproductive dysfunction induced by cyclophosphamide. The results indicate that oyster peptides exhibit a beneficial effect on reproductive injury by positively influencing the biochemical parameters of blood, the pathological state of the testes and kidneys, and reducing OS responses (Li et al., 2020). According to Zhang et al. (2021b), peptides from oyster hydrolysate can be used to prevent reproductive injury and spermatogenesis disorders induced by triptolide. Although the role of antioxidants from marine organisms has been explored as a possible treatment option for reproductive issues, few bioactive compounds have been identified, characterized and purified to elucidate their unique functions. Additionally, some mechanisms of action have remained unknown and limited numbers of marine species have been investigated for those benefits.

Infertility is defined as being unable to become pregnant after at least one year of unprotected sex (Vander Borght and Wyns, 2018). It affects approximately 8-12% of global couples during the reproductive period. Recently, Thoma et al. (2021) reported that infertility had been overlooked in sexual and reproductive health, even though 10 - 25% of couples (from 48 to 180 million people) have suffered. According to Deyhoul et al. (2017), infertility is commonly associated with reproductive system disorders or diseases, hormonal issues, aging, drinking and smoking, stress, and other unknown causes. Additionally, exposure to environmental pollutants and toxins can negatively affect reproductive cells, leading to infertility (Thoma et al., 2021). Infertility treatments vary, including conventional solutions such as hormone therapy or in vitro fertilization. However, marine natural alternatives have gained more interest since they are safe and effective solutions and provide various pharmaceutically significant bioactivities to benefit human health, including protections against reproductive health disorders.

Recent studies have confirmed the potential application of marine animal-derived bioactive compounds in supporting human fertility. Particularly, at a given dose, saponin as triterpenoid glycosides of sea cucumber, H. leucospilota can positively affect in vitro maturation of oocytes. The extracted saponin at a 1 or 2 μg/ml concentration increased follicle growth and superoxide dismutase SOD activity and inhibited ROS formation and TNF-α expression in granulosa cells. However, the mechanisms of saponin action on oocyte and granulosa cells need further investigations (Moghadam et al., 2016). Similar research has been performed to evaluate the effect of Persian Gulf Sea cucumber, H. leucospilota Brandt, body wall methanol extract on in vitro maturation of immature mouse oocytes. The results show that the extraction can enhance the maturation level of oocytes. Furthermore, the treated oocytes at 20 µg/mL of this sea cucumber extract have the highest percentage of Metaphase II stage (Khalilzadeh et al., 2016). According to Riani et al. (2017), sea cucumber also exhibits the pharmaceutical potential for enhancing the quality of male reproduction. Male mice were given the sea cucumber (Holothuria scabra) powder at 10, 30, and 50 μg of steroid/100g body weight during 12 days. The results indicate that the powders significantly improved semen concentration at a given dose of 10 μg of steroid/100 g body weight.

Zinc is an essential element for regular reproductive activity and semen quality. Zn deficiency impedes spermatogenesis, associated with sperm abnormalities and depression of sperm motility. Additionally, the serum testosterone level, seminal plasma, and total seminal zinc loss per ejaculate in young males are negatively influenced by zinc depletion in a short period (Hunt et al., 1992; Matsuda and Walanabe, 2003; Fallah et al., 2018). The oyster extract, containing significant amounts of zinc, exhibited supportive functions to reproductive health through improving embryonic development, concentrations of zinc serum and semen maturation (Matsuda and Walanabe, 2003; Miki et al., 2011). For example, Miki et al. (2011) evaluated the effects of the oyster extract on animals with low semen concentration of 1.3 x 10⁷/ml (the standard level of sperm concentration was >2 x 10⁷/ml) or low concentration of motile sperm of 1 x 10⁶/ml (the standard level of progressively motile sperm was > 5 x 10⁶/ml). The results show a significant increase in the semen concentrations that reached the standard levels after administration for 8 weeks in both treatments. Therefore, the oyster extract has pharmacological activities to address semen concerns, including dysfunction and low concentrations. According to Matsuda and Walanabe (2003), a significant decrease in body weight, testis weight and semen quality were found in male mice with zinc deficiency for 12 weeks, whereas feeding oyster extract (20, 40 or 80 g/kg of dried oyster extract) could prevent reproductive failure, embryonic defects and declined semen motility. However, those authors also suggested that other nutrients found in oyster extracts, such as taurine and glycogen, may be associated with the recovery of reproductive function.

Seahorses have been commonly used as a traditional remedy in some Asian cultures for centuries, as seahorses have the potential to cure some diseases such as infertility (Xu et al., 2014; Zhang et al., 2017; Sudirman et al., 2021). Notably, seahorse extracts showed protective effects against oligospermatism by impairing benign prostatic hyperplasia symptoms and reversing oligospermatism (Xu et al., 2014). The cyclophosphamide (CP)-induced mice fed 1.0 g/kg body weight of seahorses acetic extracts for 30 days had significantly higher epididymal sperm count and sperm motility than the control group (Xu et al., 2014). According to Sudirman et al. (2021), seahorse, H. kuda, peptide hydrolysate could prevent reproductive dysfunction in diabetic rats by improving testosterone level, follicle-stimulating hormone, luteinizing hormone and semen functions. Particularly, diabetic rats fed on seahorse hydrolysate (20 mg/kg) exhibited inhibiting lipid peroxidation, elevating antioxidant enzyme activity and restoring seminiferous tubule morphology in testes.

Bivalves such as blood clam (Scapharca broughtonii) are rich in D-aspartate and N-Methyl-D-aspartic acid (NMDA) that are found in the neuroendocrine systems and associate with hormone production (Tsesarskaia et al., 2009). D-aspartate is involved in luteinizing hormone and testosterone release, and supplementation of D-aspartate has positive effects on sperm motility (Topo et al., 2009; D’Aniello et al., 2012). According to D’Aniello et al. (2012), taking D-aspartate for two to three months can significantly improve spermatozoa count and mobility in humans. The commercial form of D-aspartate was used in humans by D’Aniello et al. (2012). However, by now, limited research has been conducted regarding the extraction, purification and uses of bivalve-derived D-aspartate and N-Methyl-D-aspartic acid (NMDA) as bioactive compounds or food supplements to support men’s fertility. Furthermore, research into identifying new bivalve species containing D-aspartate and NMDA is strongly encouraged since limited blood clam populations have been studied.

Testosterone, one of three important steroids, is produced by steroidogenesis that is essential for general wellbeing and the development of the male reproductive system (Andersen et al., 2011). Testosterone generally affects almost every organ in the body, including reproductive functions such as promoting and supporting spermatogenesis, sperm maturation, accessory organs, sexual desire and secondary sexual characteristic development (Andersen et al., 2011; Chen et al., 2019a). However, the imbalanced testosterone level has been associated with a wide range of commonly clinical diseases, including SD and a decline in male reproductive capacity (Petak et al., 2002; Chen et al., 2019a). According to statistics, low testosterone level or low sperm count occur in 35% of infertile couples (Odisho et al., 2014) and lower total serum testosterone was observed as 20%, 30% and 50% in male groups of 60, 70 and 80 years old, respectively in the Baltimore Longitudinal Study on Aging (Harman et al., 2001). In contrast, the lower total serum testosterone was found in 12.3% of men aged 40 to 70 with three or more symptoms of hypogonadism in the Massachusetts Aging Male Study report (Araujo et al., 2004) and 5.6% of men aged 30 to 70 being hypogonadal from the Boston Area Community Health Study (Araujo et al., 2007). Approximately 6.5 million American males between 30 and 79 years old will have symptomatic androgen deficiency by 2025 (Araujo et al., 2007). Various treatments, including hormone replacement therapy, have been explored to address reproductive and sexual issues caused by low hormone levels (Chen et al., 2019a).

Sea cucumber has a bioactive potency that could improve testosterone level and sperm quality and quantity (Golestanin et al., 2016; Ikram et al., 2018). The extracts of sea cucumber positively influenced the production of steroid hormones in rats, fish, and roosters. For example, Ikram et al. (2018) investigated the effects of sea cucumber, Scincus scincus extract on testosterone secretion and abundance, and semen quality of rats. The animals were fed with experimental diets containing 12% of either body (SB) or head (SH) of sea cucumber. The body weight, the relative weight of the testes and testosterone level in experimental rats were significantly improved in comparison with control groups. Furthermore, a significant increase in semen concentration (235.37x10⁶/ml) and motility (62%) were observed in those sea cucumber treatments. In other animal studies, injection of alcoholic extract (200 mg/kg) or non-polar extract (100 and 200 mg/kg) of Persian Gulf Sea cucumber significantly dismissed body testosterone and cholesterol levels in the molly fish (Golestani et al., 2016). The rooters fed 0.5 ml of dry/frozen sandfish steroid 0.4g/ml were able to elevate testosterone and cholesterol levels in blood serum, fastening secondary reproduction characteristics and promoting growth (Riani et al., 2013).

Oysters contain various bioactive compounds, a great source of protein and trace elements such as zinc, taurine, which may support sexual development, sexual function, hormone production, and reproductive cells (Jin et al., 2021a; Hao et al., 2022). In recent years, research using animal models has confirmed that oyster peptides have a strong antioxidant effect and can stimulate testosterone secretion and enhance sexual function (Zhang et al., 2018; Chen et al., 2019b; Jin et al., 2021a). Remarkably, the treatment with a medium (1.2 g/kg bw) dose of oyster oligopeptide had positive effects on testosterone production by reducing OS in testis and preventing the formation of cyclophosphamide-induced partial androgen deficiency of ageing males (Jin et al., 2021a). According to Zhang et al. (2021a), oyster peptide (in which >95% peptides were <3000 Da) from Crassostrea gigas can improve the serum testosterone and cyclic adenosine monophosphate (cAMP) in male mice.

Seahorse-derived hydrolysates have positive effects on male reproductive health due to improving the serum testosterone level (Kim et al., 2016b). Male mice with a daily intake of hydrolysates from seahorse, H. abdominalis for 12 weeks showed increased sperm motility and testosterone level. It was suggested that the hydrolysates stimulate the proliferation of TM3 cells via the AKT, ERK, and JNK pathways (Kim et al., 2016b). In another research, Park et al. (2015) reported that water extract of seahorse Hippocampus significantly increased the absolute and relative testes weight, semen parameters, and testosterone concentration in cyclophosphamide (CP) treated animals compared to the control group.

Sexuality is one of the critical indicators for human health and wellbeing that significantly contributes to the quality of life. Good health is commonly linked to normal or healthy sexual function, whereas poor life quality, significant psychological distress and many diseases are associated with sexual issues (Balon, 2017; Soldati et al., 2020). SD is recognized as incapacity to sexually respond or experience sexual pleasure despite adequate stimulation (Soldati et al., 2020). It is generally related to disorders in desire, arousal, orgasm, and pain in women, while ED, premature/delayed ejaculation, hypoactive sexual desire disorder were commonly found in men (Krakowsky and Grober, 2018; Chen et al., 2019a; Soldati et al., 2020). Between 20 and 30% of adult men worldwide experienced at least one type of sexual disorder, and the number was higher with an increase in age (Lewis et al., 2010; Berger et al., 2016). Importantly, males at the reproductive stage frequently suffer SD, which causes infertility in some instances (Lotti and Maggi, 2018). ED, one of the most common SD, were observed in 31.7%, 179 out of 810 Australian men from 35 to 80-year-old residing in northern and western Adelaide, Australia (Martin et al., 2014). Regarding women’s sexual health, SD was reported to negatively influence up to 41% of women at the reproductive stage worldwide (McCool-Myers et al., 2018). According to certain studies, 5.8% of women reported symptoms of SD, while 15.5% of females experienced lifelong SD in the United Kingdom (Burri and Spector, 2011). Australian research indicates that 36% of females suffered at least one type of sexual difficulty a year (Smith et al., 2012). Among the women age group of 19-40 years old, more than haft of females (53%) had at least one symptom of SD; while it was 31% for males in Sweden (Ljungman et al., 2020). Furthermore, Ambler et al. (2012) reported that the prevalence of SD was between 25% and 63%, and the figures were even higher in postmenopausal women with rates between 68% and 86.5%. The solutions for addressing sexual problems have been investigated, including synthesized compounds such as sildenafil, tadalafil, and phosphodiesterase-5 (PDE5) inhibitors (Balon, 2017; Hess and Boehmer, 2020). However, the side effects of taking synthesised compounds, including anxiety, headaches, high blood pressure or increased heart rate, have been recently reported (Hess and Boehmer, 2020). Therefore, the use of natural alternatives and their bioactive components is a promising solution and is highly recommended in the future study.

Oysters are rich in nutritional and medicinal value that are believed to have significant effects on nourishing kidneys and remitting fatigue in traditional Chinese medicine (Luo et al., 2021; Zhang et al., 2019). They are also traditionally used as an aphrodisiac in Western countries (Ridzwan et al., 2013). Recent studies have reported its medical applications in improving male sexual function. For example, Chen et al. (2019b) reported that small-molecule polypeptide of Pacific oysters could enhance the sexual function of male mice by improving the mating ability, weight and organ coefficient of gonad and sperm qualities, increasing the content of cholesterol and sex hormones in serum and nitric oxide (NO) in the penis, and improving the expression of sexual function-related genes in mice. Moreover, the degree of sexual function enhancement could have dose-dependency within a certain range. Zhang et al. (2018) suggested that feeding male mice with oyster oligopeptides, together with walnut oligopeptides and yam polysaccharides (640 + 110 + 220 mg/kg bw) could improve the sexual function in male mice. In a similar study, the combination oligopeptides isolated from ginseng (GOPs) and oyster (OOPs) at the level of 62.5 mg kg⁻¹ GOPs or 60.0 mg kg⁻¹ OOPs had the best effects in improving male sexual behavior, serum NO, testosterone, and cyclic guanosine monophosphate (cGMP) contents and decreasing PDE5 content. These oligopeptides could be considered a natural alternative for enhancing male sexual function (Li et al., 2021). Feeding oyster hydrolysate supplementation (0.617, 0.308, 0.103 g/kg bw per day) had significant effects on alleviating ED and promoted the synthesis of testosterone by stimulating the synthesis of luteinizing hormone, which then increased the serum NO content through the NO-cyclic guanosine monophosphate (NO-cGMP) signaling pathway (Wang et al., 2020). Interestingly, the research results indicate that fresh oyster extract can also promote and support healthy sexual function and endurance by inhibiting the activity of PDE5 (Li et al., 2021). PDE5 inhibitors are a group of medications commonly used to treat ED or SD in men (Ahmed et al., 2021).

Seahorse, Hippocampus species, have been widely used as a traditional folk medicine for ED treatment, enhancing the intercourse ability and sexual functions, which have a long history in some Asian cultures (Chen et al., 2015; Cui et al., 2021). Those pharmacology effects lead to some available commercial products on the markets (Chen et al., 2015). Notably, the hormone-like activity of Hippocampus was investigated for treating ED during the past years. The significant enhancement in the intercourse ability and the sexual functions were observed in male rats fed on Hippocampus capsule twice a day for 12 days at doses of 0.095, 0.135 and 0.405 g/kg (Xu et al., 2003). Similarly, rats given doses of 0.54, 0.70 and 1.40 g/kg of the Haima Zhuangyang capsule for 20 days significantly had more mating activities but reduced the incubation period for the erection and supported kidney function (Lu et al., 2001). In another report, the Hippocampus capsule increased the sexual activities in mature male rats and reduced males’ latency catching females and ejaculation (Xu et al., 2003).

Echiurans, known as sea worms, commonly found in North China, Korea, and Japan, are also known to have positive effects on ED (Ryu et al., 2014; Kim et al., 2016a). Kim et al. (2016a) evaluated the effects of the active peptide from spoon worm, Urechis unicinctus by high temperature/pressure and ultra-wave assisted lysis on ED in streptozotocin-induced diabetic rats. The results indicate that active peptides of spoon worm could prevent ED in a streptozotocin-induced diabetic rat by improving levels of NO and cGMP, while reducing activity and expression eNOS and nNOS. The in vitro study by Ryu et al. (2014) also confirms that the isolated peptide from spoon worm may enhance erectile function by increasing the levels of NO and cGMP.

Low sexual desire/pleasure, loss of libido or sexual attraction are usual sexual concerns that may occur in many men and women at some stages of their life. According to Parish and Hahn (2016), quality of life, general happiness and satisfaction with partners, positive emotion are negatively affected by the loss of sexual desire. Poor relationships, aging, stress, anxiety, and exhaustion are the major causes. Besides, it is also linked to other health issues (Parish and Hahn, 2016). The aphrodisiacs are substances that have generally been used to increase libido, potency, sexual attraction, sexual pleasure and sexual performance in both males and females (Sandroni, 2001; Bella and Shamloul., 2014; Hess and Boehmer, 2020). Synthesized compounds such as Phosphodiesterase V inhibitors (sildenafil, tadalafil, and vardenafil), Yohimbine, Steroid hormones (dehydroepiandrosterone – DHEA), Flibanserin, Arginine, Phenethylamines, Gamma-hydroxybutyric acid (GHB) and its precursors have been increasingly popular in recent years to enhance erectile function, sexual arousal and desire (Hess and Boehmer, 2020). However, intensive side effects and intoxications have been recently reported by Hess and Boehmer (2020) for some synthetic products that cause an increasing demand for safe and effective sources such as ginko, ashwaganda, maca root, panax ginseng and seafood.

There is growing scientific evidence to confirm the aphrodisiac values of sea animals. Marine organisms such as oysters, sea horses, spoon worms and sea slugs have been reported to possess aphrodisiac values (Ridzwan et al., 2013; Rosa et al., 2013; Hashim et al., 2014; Kim et al., 2016a). Oysters have been taken to enhance sexual desire and performance since ancient times and there are available scientific evidence to confirm the supporting functions of this bivalve species. For example, Ridzwan et al. (2013) experimented with screening the aphrodisiac property in the local oyster of Crassostrea iredalei. Mice treated with oyster ethanol extract exhibited mating behavior at the dose levels of 50, 100 and 200 mg/kg compared to aqueous extract. According to Zhang et al. (2019), oyster meat and its hydrolysates showed antioxidant and aphrodisiac activities and significantly improved sexual performance both in vitro and in vivo. The enhancement of sexual behavior in experimental animals occurred at a dose of 250 mg/kg. Sea slug, Aplysia dactylomela, which shares the same phylum Mollusca with oyster, also exhibited the aphrodisiac function in the rat model due to a high level of steroids. The lipid extracts (50 mg/kg) exhibit aphrodisiac properties due to increasing mating behavior frequency (Hashim et al., 2014). According to Paick et al. (2016), rats offered dried sea worm, Urechis unicinctus, hydrolysate power significantly increased the frequency of sexual behavior such as mount and ejaculation. Similarly, seahorse species also exhibit the function of aphrodisiac activity. According to Rosa et al. (2013), other medicinal uses and properties of seahorses include promoting sexual desire, aiding in ED treatment, improving the sexual potency of older men and increasing sexual potency. Those evidence promote interests in using the marine-derived aphrodisiac property as an alternative therapy to improve male sexual performance.