Aquaculture has been known for millennia, when the trend of captive fish rearing began, and it is now playing a crucial role in solving the world food crisis, particularly in meeting the protein demand [1]. However, broodstock management, which includes the optimization of critical reproductive processes, such as nutrition, maturation, egg and sperm production, and spawning, remains a major obstacle to the advancement of the aquaculture industry. Captive broodstocks are most vulnerable to the disruption of reproductive activities by hormonal imbalance and unfavorable environmental parameters [2] resulting in reproductive dysfunction. Such reproductive impairments include no or poor-quality egg or sperm production, defective or weak spawn, less growth and high mortality of fry, and sometimes mortality of the brood. Reproductive dysfunctions can be triggered by direct or indirect variations of the gametes and endocrine system, captivity-induced stress, unsuitability of the spawning environment, and deficiencies in the nutritional profiles of feeds ^[3][4][3,4]. Some taxonomic groups of fishes are far more sensitive to such inhibitory influences than others. Reproductive dysfunction is common in Anguilla spp. (catadromous eels), Seriola spp. (greater amberjack and Japanese yellowtail), Caranx ignobilis (giant trevally), Epinephelus spp. (groupers) and Thunnus spp. (bluefin tuna) [5], Anoplopoma fimbria (Sablefish) [6], and Oncorhynchus mykiss (Rainbow trout) [2].

To avoid reproductive dysfunction, scientific management of broodstock animals ensures proper physiology, immunology, reproductive enzymes pathways activation, and transcription of specific reproductive genes. Many commercial farms seek to maintain healthy broodstocks by supplementation with probiotics to increase reproductive enzymes activities and gene transcription, but dysfunction remains fairly common during breeding seasons ^[7][8][7,8]. Moreover, epigenetic mechanisms include DNA methylation, histone modification, and noncoding RNA action underlying various processes have recently received considerable attention in aquaculture and offer some promise in the amelioration of breeding performance [9].

The term epigenetics literally means “above” or “on top of” genetics, and epigenetic traits refer to stable heritable phenotypes resulting from changes in the status of chromosomes without alteration of DNA sequences [10]. Epigenetic reprogramming underpins many developmental processes such as gametogenesis and embryogenesis, foundation of environment regulating events of fish sex differentiation, providing a linkage between phenotypic and metabolic changes during domestication [11]. In several studies, epigenetic inheritance was found to be more feasible in fish as compared with terrestrial animals ^[12][13][14][12,13,14]. Epigenetic information has the potential to contribute to lower disease prevalence and the potential eradication of the use of antibiotics in commercial aquaculture [15]. Sperm quality has been linked to DNA methylation in spermatozoa and in Morone saxatilis (striped bass) sperm DNA methylation has a positive relationship with male reproductive capacity [16]. Epigenetics influence fish sex determination and differentiation, facilitating interactions between these processes with other surroundings [17]. When it comes to valuable fish species, such as grouper, it is essential to know sex patterns, especially when their sex is changed. In aquaculture, a stable and predictable mating system is critical for healthy fry production [9] and alterations in DNA methylation patterns triggered by higher temperatures can lead to more masculine traits in females ^[18][19][18,19]. Although epigenetics has huge potential, studies on economically important aquaculture species remain preliminary, and many unanswered questions remain ^[12][20][12,20]. An understanding of epigenetic mechanisms for commercial species could contribute to expansions and improvements in the economic viability of large-scale aquaculture.

Aquaculture technology has developed a positive view of probiotics application as an alternative to the application of synthetic antibiotics or chemicals ^[21][22][23][21,22,23]. Recognition of advantages of practical use of probiotics has grown in light of evidence of upregulation of fish growth, stress adaptation, immune modulation, and disease resistance ^[24][25][24,25]. Probiotics are defined as “live microorganisms administrated at an appropriate concentration that exert beneficial effects on host health and immune parameters” [26]. Ghosh, et al. [27] initially reported probiotics capacity to restore viable nutrients in female live-bearing ornamental fishes such as Poecilia reticulata (Guppy), P. sphenops (molly), Xiphophorus helleri (Swordtail) and X. maculatus (Platyfish). A later investigation was also carried out in X. helleri [28], Danio rerio (Zebrafish) ^{[29][30][31][32][33][34]}[29,30,31,32,33,34], Carassius auratus (Goldfish) [35], and Fundulus heteroclitus (Killifish) [36]. Limited probiotics studies were also conducted to improve reproductive performance in commercial fishes such as Oreochromis niloticus (Nile Tilapia) [37], O. mykiss [38], Ompok pabda (Butter catfish) [39], Clarias gariepinus (African catfish) [40] and A. anguilla (European eel) [41] on the subject of reproductive indicators such as fecundity (Fec), hatching rate (HR), gamete quality, gonadosomatic index (GSI), fertilization rate (FR), and survival rate (SR). Pathogenic infections often leading to mortality of brood or offspring may be unnoticed by hatchery managers. Synthetic antibiotics or chemical applications to control infection may lead to mass environmental bacterial killing, antibiotic deposition in fish body and the generation of antibiotic-resistant pathogens ^[42][43][42,43]. As a result, probiotics may be a favorable option for broodstocks and fry for the control of infections and for improved reproductive success [44]. The use of probiotics helps to stabilize and diversify the intestinal microbial community, leading to improved reproduction processes through activation of different hormones, enzymes, and genes transcription resulting better FR, HR, SR, and larval growth ^[7][38][7,38].

2. Fish Reproductive Dysfunctions

Globally, aquaculture is continually striving for the consistency of physiological integrity of fingerlings through standardized reproductive programmes, which are a key objective for sustainable aquaculture [45]. Brood fish rearing and their management strategies have been considered as vital for aquaculture production for the last three decades. Generally, many species of captive fishes do not perform normal reproduction (especially females), a phenomenon potentially caused by a lack of natural spawning stimuli, specifically failure of oocyte maturation ^[46][47][46,47]. Supplied protein, fatty acids, lipid, vitamins, especially E and C, and carotenoids also influence fish Fec, FR, HR, and larval development ^[48][49][48,49]. Moreover, presence of chemical fertilizers, antibiotics, hormones and industrial effluents, environmental degradation, and frequent fluctuation of temperature in nature and captivity suppress the immunity and beneficial microbial activity in broodstock fishes, making them more susceptible to infectious disease ^{[27][50][51][52]}[27,50,51,52]. Hypothalamus, pituitary, and gonads form the hypothalamic-pituitary-gonadal (HPG) axis, which regulates reproductive function in most fishes [53]. The hypothalamus and the pituitary glands modulate the production of pituitary gonadotropins luteinizing hormone (LH) and follicle stimulating hormone (FSH), and gonadal sex steroids (SS) regulate vitellogenesis and oocyte maturation. FSH and LH have been confirmed to figure importantly in oocyte growth and maturation [54]. Gioacchini et al. [7] have categorized three types of female broodstocks reproductive dysfunctions based on the affected pattern of reproductive cycle whereas, Selvaraj, et al. [55] documented two modes of dysfunction of teleost fishes (Figure 1). Both groups of investigators associated the most disruptive reproductive dysfunctions occurred with the vitellogenic phase, as exemplified by failed vitellogenesis in Anguilla spp. and Seriola spp. [56] and Mugil cephalus (Grey Mullet) [57]. The second mode is categorized as the inability to reach final oocyte maturation to ovulation as seen in farmed white and striped bass ^[58][59][60][58,59,60] and in Cyprinidae [61]. The third set of dysfunctions leads to failures to spawn in the breeding season; sometimes E. aeneus, M. saxatilis, and Dentex dentex (common dentex) females may release eggs after ovulations without exhibiting characteristic breeding behavior ^[7][62][7,62]. Under some circumstances, cultured salmonids fail to complete the reproductive cycle and eggs in the abdominal cavity are reabsorbed over the following months [63]. These are examples of failures among female broodstocks that do not appear to be accompanied by reproductive problems that can be attributed to male fishes. One common problem faced by cultured male fishes is low quantity or quality of milt production during spermiation [60]. The presence of both male and female germ cells in the testis tissue is referred to as an intersex state caused by endocrine disruption through chemical exposure and hormonal imbalance [64]. The histopathological assessment of gonadal tissue during the development stage allows the detection of intersex reproductive dysfunction in male Japanese medaka (Oryzias latipes) [65].