Abstract

Adaptation of reproductive activity to environmental changes is essential for breeding success and offspring survival. In mammals, the reproductive system displays regular cycles of activation and inactivation which are synchronized with seasonal and/or daily rhythms in environmental factors, notably light intensity and duration. Thus, most species adapt their breeding activity along the year to ensure that birth and weaning of the offspring occur at a time when resources are optimal. Additionally, female reproductive activity is highest at the beginning of the active phase during the period of full oocyte maturation, in order to improve breeding success. In reproductive physiology, it is therefore fundamental to delineate how geophysical signals are integrated in the hypothalamo-pituitary-gonadal axis, notably by the neurons expressing gonadotropin releasing hormone (GnRH). Several neurochemicals have been reported to regulate GnRH neuronal activity, but recently two hypothalamic neuropeptides belonging to the superfamily of (Arg)(Phe)-amide peptides, RFRP-3 and kisspeptin, have emerged as critical for the integration of environmental cues within the reproductive axis. The goal of this review is to survey the current understanding of the role played by RFRP-3 in the temporal regulation of reproduction, and consider how its effect might combine with that of kisspeptin to improve the synchronization of reproduction to environmental challenges.

Highlights

  • Specialty section: This article was submitted to Experimental Endocrinology, a section of the journal Frontiers in Endocrinology

  • RFamide-related peptides (RFRP)-3 is consistently reported to regulate reproductive axis function, the effect on gonadotropin releasing hormone (GnRH) neuronal activity and gonadotropin secretion is highly dependent on species, sex and environmental conditions

  • This complexity in the impact of RFRP-3 has hampered the ability to determine the precise role of this neuropeptide in the synchronization of the preovulatory LH surge in females and long-term breeding in seasonal species

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Summary

Daily and Ovarian Rhythms in Female Reproduction

Successful female reproduction requires the activation of specific neuronal and hormonal pathways in order to synchronize ovulation with maximal locomotor activity and optimal arousal state. In striped hamsters (Cricetulus barabensis), the highest expression of Rfrp is observed in breeding males, whereas breeding females exhibit lowest mRNA expression, pointing to disparate seasonal roles of RFRP-3 between the sexes [153] These data demonstrate that seasonal/photoperiodic variation in RFRP-3 expression is highly conserved among seasonal mammals with higher levels in LD summer as compared to SD winter, whether animals are LD or SD breeders (Figure 2). These findings indicate that melatonin uses similar mechanisms to regulate RFRP-3 expression in all seasonal species and that the switch driving LD or SD breeding activity may be downstream of RFRP-3 neurons. Further studies are needed to better understand the downstream effect of RFRP-3 on GnRH neurons and gonadotropin secretion and reveal why this neuropeptide displays opposite actions according to species, sex, and photoperiod

Are RFRP Neurons the Site of Seasonal Changes in Hypothalamic TH?
Findings
GENERAL CONCLUSIONS
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