A Review on Environmental Contaminants-Related Fertility Threat in Male Fishes: Effects and Possible Mechanisms of Action Learned from Wildlife and Laboratory Studies.

Increasing global rates of diminished fertility in males has been suggested to be associated with exposure to environmental contaminants (ECs). The aquatic environments are the final repository of ECs. As the reproductive system is conserved in vertebrates, studies on the effects of ECs on fertility endpoints in fishes provide us with valuable information to establish biomarkers in risk assessment of ECs, and to understand the ECs-related fertility threat. The aim of the present review was to evaluate associations between ECs and fertility determinants to better understand ECs-related male fertility threat in male fishes. Wildlife studies show that the reproductive system has been affected in fishes sampled from the polluted aquatic environment. The laboratory studies show the potency of ECs including natural and synthetic hormones, alkylphenols, bisphenols, plasticizers, pesticides, pharmaceutical, alkylating, and organotin agents to affect fertility determinants, resulting in diminished fertility at environmentally relevant concentrations. Both wildlife and laboratory studies reveal that ECs adverse effects on male fertility are associated with a decrease in sperm production, damage to sperm morphology, alternations in sperm genome, and decrease in sperm motility kinetics. The efficiency of ECs to affect sperm quality and male fertility highly depends on the concentration of the contaminants and the duration of exposure. Our review highlights that the number of contaminants examined over fertility tests are much lower than the number of contaminants detected in our environment. The ECs effects on fertility are largely unknown when fishes are exposed to the contaminants at early developmental stages. The review suggests the urgent need to examine ECs effects on male fertility when a fish is exposed at different developmental stages in a single or combination protocol. The ECs effects on the sperm genome are largely unknown to understand ECs-related inheritance of reproductive disorders transmitted to the progeny. To elucidate modes of action of ECs on sperm motility, it is needed to study functional morphology of the motility apparatus and to investigate ECs-disrupted motility signaling.

Rfamide-related peptide-3 suppresses the substance P-induced promotion of the reproductive performance in female rats modulating hypothalamic Kisspeptin expression.

RFamide-related peptide-3 (RFRP-3) has been postulated as the suppressor of the reproductive axis at hypothalamic, pituitary and gonadal levels. Considering the hypothalamic level, RFRP-3 can suppress the activity of gonadotropin-releasing hormone (GnRH) neurons and their upstream neuronal stimulator, namely; the kisspeptin neurons. The effects of the RFRP-3 on the other regulators of GnRH neurons, however, are not completely investigated. Furthermore, substance P (SP) has been known as one of the coordinators of GnRH/ luteinizing hormone (LH) and the kisspeptin/G protein-coupled receptor 54 (GPR54) systems. The present study was aimed at investigating the impacts of RFRP-3 on the effects of SP on the reproductive performance in ovariectomized female rats. After intracerebroventricular (ICV) cannulation, the rats were subjected to the ICV injection of either SP or RFRP-3 and simultaneous injection of them and their selective antagonists. Blood and hypothalamic samplings and also sexual behavioral test were carried out on two main groups of rats. The analyses of the results of LH radioimmunoassay, gene expression assay for hypothalamic Gnrh1, Kisspeptin and Gpr54 accompanied by sexual behavioral examination revealed that the SP administration promotes reproductive behavior and GnRH/LH system and upregulates Kisspeptin expression. The RFRP-3 administration suppressed reproductive behavior, GnRH / LH system and Kisspeptin expression; however, the simultaneous injection of SP and RFRP-3 was devoid of significant alterations in the assessed parameters. The results showed that RFRP-3 can modulates the impacts of SP on the reproductive performance in ovariectomized female rats in part through adjusting Kisspeptin expression.

The Impact of Morphine on Reproductive Activity in Male Rats Is Regulated by Rf-Amid-Related Peptide-3 and Substance P Adjusting Hypothalamic Kisspeptin Expression.

Obviously, opiates (e.g., morphine) are associated with the suppression and dysfunction of reproductive axis. It has been reported that substance P (SP) and RF-amid-related peptide-3 (RFRP-3) can exhibit anti-opioid effects in some regions of the nervous system. Moreover, SP and RFRP-3 are deemed as neuropeptides which exert modulatory and regulatory impacts on the function of the reproductive axis. The precise interactions of morphine with SP or RFRP-3 on the parameters of the reproductive activity, however, are not fully known. The present study was aimed to determine the impacts of the interaction of morphine either with SP or RFRP-3 on the hormonal and behavioral parameters of reproductive activity in male rats. In addition, it was aimed at determining whether the effects of these interactions rely on kisspeptin/G protein coupled receptor 54 (GPR54) pathway as the main upstream pulse generator and the mediator of the function of many inputs of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) system or not. Altogether, the resulted data from the sexual behavior tests, radioimmunoassay of LH/testosterone, and real-time quantitative PCR for the assessment of the expression of hypothalamic Kiss1, Gpr54, and Gnrh1 genes following concomitant administration of morphine with SP or RFRP-3 revealed that the suppressing effects of morphine on the parameters of reproductive axis activity can be affected by the administration of either RFRP-3 or SP. It is advocated that SP and RFRP-3, by the modulation of the expression of hypothalamic Kiss1, can possibly antagonize the effects of morphine on GnRH/LH system and sexual behavior.