Table 1. Observational and functional studies of RFRP3 and orthologs in vertebrate ovaries.
| Cit. | Class | Order | Species/Strain | Approach | Summary of findings |
|---|---|---|---|---|---|
| Observational findings | |||||
| Osugi et al. (2012) | Hyperoartia | Petromyzontiformes | Petromyzon marinus | PCR | RFRP3 expressed in the ovary |
| Biran et al. (2014) | Osteichthyes | Cichliformes | Oreochromis niloticus | PCR | RFRP3 and receptor expressed in the ovary |
| Qi et al. (2013) | Osteichthyes | Cypriniformes | Carassius auratus | in situ | RFRP3 receptor expression abundant in early-stage follicles |
| Zhang et al. (2010) | Osteichthyes | Cypriniformes | Danio rerio | PCR | RFRP3 and RFRP3-R expressed in the ovary |
| Corchuelo et al. (2017) | Osteichthyes | Cypriniformes | Danio rerio | PCR/in situ | RFRP3 expression in the ovary highest during primary growth of follicles, and lower during later stages of follicle growth (PCR); RFRP3 expressed in the granulosa cells of vitellogenic follicles (in situ) |
| Paullada-Salmerón et al. (2016) | Osteichthyes | Perciformes | Dicentrarchus labrax | PCR | RFRP3 expressed in the ovary (very low) |
| Wang et al. (2018) | Osteichthyes | Pleuronectiformes | Cynoglossus semilaevis | PCR | RFRP3 expressed in ovary; RFRP3 expression ten-times more intense during previtellogenesis relative to other stages of ovary maturation |
| Shahjahan et al. (2011) | Osteichthyes | Tetraodontiformes | Takifugu niphobles | PCR | RFRP3 expression absent in the ovary |
| Singh et al. (2008) | Reptilia | Squamata | Calotes versicolor | IHC/slot blot | RFRP3-ir highest in the stroma of resting-phase ovaries (IHC); RFRP3-ir present in GCs of the dominant follicle during recrudescence and the oocyte of the dominant follicle during folliculogenesis (IHC); RFRP3 protein abundance increases across vitellogenesis, ovulation, and regression, with abundance highest in resting-phase ovaries (slot blot) |
| Bentley et al. (2008) | Aves | Galliformes | Coturnix japonica | PCR | RFRP3 and RFRP3-R expressed in the ovary (PCR); |
| Maddineni et al. (2008) | Aves | Galliformes |
Gallus gallus domesticus/ White Leghorn |
PCR | RFRP3-R expression in TCs decreases with follicle maturation; RFRP3-R is more abundant in GCs of all follicles than in TCs |
| Bentley et al. (2008) | Aves | Passeriformes | Zonotrichia leucophrys Gambelii | in vivo & in vitro receptor fluorography/IHC | Bindings sites for RFRP3 found in the GCs of ovarian follicles (in vivo & in vitro receptor fluorography); RFRP3-ir localized to ovarian GCs (IHC) |
| Bentley et al. (2008) | Aves | Passeriformes | Sturnus vulgaris | in vivo receptor fluorography/PCR/IHC | Bindings sites for RFRP3 in the GCs of ovarian follicles (in vivo receptor fluorography); RFRP3 and RFRP3-R expressed in the ovary (PCR); RFRP3-ir localized to ovarian GCs (IHC) |
| Li et al. (2014) | Mammalia | Artiodactyla | Ovis aries/Dorper ×Hu F1 | PCR/IHC | RFRP3 expression in the ovary (PCR); RFRP3 expressed in oocytes (IHC); RFRP3 expressed in GCs tertiary follicles only (IHC) |
| Li et al. (2012) | Mammalia | Artiodactyla | Sus scrofa domesticus/ Suzhong (PCR) Large white cross-bred (IHC) | PCR/IHC | RFRP3 expression in ovary most abundant during proestrous and least abundant during estrous (PCR); RFRP3-R expression in the ovary most abundant at estrous and least abundant during diestrous (PCR); Most intense RFRP3-ir found in the GCs during estrous; RFRP3-ir also found in TCs, and CL (IHC); RFRP3-R-ir most intense in the TCs and GCs of mature follicles during estrous; RFRP3-R-ir also found in the CL (IHC) |
| Fang et al. (2014) | Mammalia | Artiodactyla | Sus scrofa domesticus/ Yorkshire | PCR | RFRP3 expressed in the pubertal ovary |
| Singh et al. (2011) | Mammalia | Rodentia | Mus musculus domesticus/ Parkes | IHC | RFRP3-ir greatest in non-luteolytic CLs and the GCs/TCs of mature follicles |
| Mammalia Rodentia | Rattus norvegicus domesticus/ | IHC | RFRP3-ir present in the interstitial tissues and GCs of antral follicles; low RFRP3-ir in the CL | ||
| Squicciarini et al. (2018) | Mammalia | Rodentia | Rattus norvegicus domesticus/ Sprague-Dawley | IHC | RFRP3-ir present in the interstitial tissues and GCs of antral follicles; low RFRP3-ir in the CL |
| Oishi et al. (2012) | Mammalia | Primates | Homo erectus | IHC | RFRP3 and RFRP3-R present in CLs and GCs/TCs of pre-ovulatory follicles |
| McGuire & Bentley (2010) | Mammalia | Primates | Macaca mulatta | in situ | RFRP3 and RFRP3-R expressed in GCs and oocytes |
| Functional findings | |||||
| Wang et al. (2017) | Osteichthyes | Perciformes | Epinephelus coioides | Ovarian explant | RFRP3(I) increases expression of StAR and 3βHSD; RFRP3(II) increases expression of LHR |
| Singh et al. (2008) | Reptilia | Squamata | Calotes versicolor | Ovarian explant | RFRP3 decreases expression of GnRH-R in the ovary |
| Maddineni et al. (2008) | Aves | Galliformes | Gallus gallus domesticus/ White Leghorn | Isolated granulosa cells | RFRP3 decreases cell survival at 10 and 1000 nM, but only in the absence of FSH |
| Li et al. (2013) | Mammalia | Artiodactyla | Sus scrofa domesticus/ Large White | Isolated granulosa cells | RFRP3 at 1000 and 0.1 nM groups exerts non-dose dependent inhibition of E2 production; RFRP3 has no effect on P4 production; RFRP3 exerts dose-dependent inhibition of ERK and PCNA expression. |
| Wang, Li & Hu (2018) | Mammalia | Artiodactyla | Sus scrofa domesticus/ Unknown | Isolated granulosa cells | RFRP3 dose-dependently inhibits GC proliferation; RFRP3 induces cell cycle arrest in the G2/M phase |
| Singh et al. (2011) | Mammalia | Rodentia | Mus musculus domesticus/ Parkes | Ovarian explant | RFRP3 dose-dependently inhibits GnRH-1-R expression in the ovary |
| Singh, Krishna & Tsutsui (2011) | Mammalia | Rodentia | Mus musculus domesticus/ Parkes | Ovarian explant | RFRP3 inhibits P4 production; RFRP3 decreases the expression of StAR and 3βHSD |
| Squicciarini et al. (2018) | Mammalia | Rodentia |
Rattus norvegicus domesticus/ Sprague-Dawley |
Ovarian explant | RFRP3 decreases P4 & T production only under the presence of LH |
| Squicciarini et al. (2018) | Mammalia | Rodentia | Rattus norvegicus domesticus/ Sprague-Dawley | Peristaltic pump | RFRP3 treatment is associated with larger CLs in the ovary |
| Oishi et al. (2012) | Mammalia | Primates | Homo erectus | Isolated granulosa cells | RFRP3 dose-dependently inhibits P4 accumulation in the presence of gonadotropins; RFRP3 inhibits StAR expression in the presence of gonadotropins; RFRP3 has no effect on steroid accumulation or steroidogenic gene expression when gonadotropins are not present |
Notes.
Abbreviations used in table
- 3βHSD
- 3-beta-hydroxysteroid dehydrogenase
- CL
- corpora lutea
- E2
- estradiol
- ERK
- extracellular regulated kinases
- FSH
- follicle stimulating hormone
- GC
- granulosa cell
- RFRP3
- RF-amide related peptide3 used throughout table for simplicity for all genes in the LPXRFa, GnIHand RFRP-3 gene family
- RFRP3-ir
- RFRP3 immunoreactivity
- RFRP3-R:
- RFRP3 receptor
- RFRP3-R-ir
- RFRP3 receptor immunoreactivity
- GnRH-1-R
- receptor for gonadotropin-inhibitory hormone-1
- IHC
- Immunohistochemistry
- LH
- luteinizing hormone
- LHR
- luteinizing hormone receptor
- P4
- Progesterones
- PCNA
- proliferating cell nuclear antigen
- PCR
- polymerase chain reaction
- StAR
- Steroidogenic acute regulatory protein
- T
- testosterone
- TC
- theca cell