title: Dynamic Regulation of Hypothalamic DMXL2, KISS1, and RFRP Expression During Postnatal Development in Non-Human Primates.
abstract: The neurobiological mechanism of puberty onset in primates is currently only partly understood. A recent study reported an important role of Dmx-like 2 (DMXL2), a gene encoding rabconnectin-3α vesicular protein, in human subjects with mental retardation and neuroendocrine impairment of reproduction. To further characterize the potential role of DMXL2 in the regulation of reproduction, we analyzed the expression of DMXL2 in hypothalami of newborn, infantile, juvenile, pubertal, and postpubertal female and male common marmoset monkeys. Additionally, as the relative hypothalamic levels of gonadotropin-inhibitory hormone (GnIH) transcript during postnatal development are unknown in primates, we also quantified messenger RNA (mRNA) levels of RFRP, a gene encoding GnIH. Moreover, the transcript levels of kisspeptin, a well-known regulator of the hypothalamic neurohormonal axis controlling reproduction, were also checked. Transcript and protein levels of DMXL2 and Kiss1 transcript levels increase from the newborn to the infantile and from the juvenile (prepubertal) to the pubertal and the postpubertal period. We also noted a clear upsurge in RFRP transcript levels in the prepubertal period. In conclusion, the hypothalamic expressions of Kiss1 and DMXL2 mRNA increase during infantile, pubertal, and adult stages compared to newborn and juvenile stages in common marmoset monkeys. In contrast, the expression of RFRP mRNA upsurges in juvenile monkeys. Further mechanistic studies are needed to characterize the potential inhibitory role of the GnIH-GPR147 signaling in the prepubertal period and the role of DMXL2 in the molecular cascade regulating the neuroendocrine reproductive axis in primates.
authors.affiliation: Platform Degenerative Diseases, German Primate Center, Kellnerweg 4, 37077, Göttingen, Germany. fazalendo@gmail.com.
authors.forename: Fazal
authors.initials: F
authors.lastname: Wahab
authors.affiliation: Platform Degenerative Diseases, German Primate Center, Kellnerweg 4, 37077, Göttingen, Germany.
authors.forename: Charis
authors.initials: C
authors.lastname: Drummer
authors.affiliation: Institute of Reproduction and Regenerative Biology, Centre of Reproductive Medicine and Andrology, Albert-Schweitzer-Campus 1, Building D11, 48149, Münster, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schlatt
authors.affiliation: Platform Degenerative Diseases, German Primate Center, Kellnerweg 4, 37077, Göttingen, Germany. rbehr@dpz.eu.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Behr
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002144:Callithrix; D005260:Female; D015870:Gene Expression; D007028:Hypothalamic Hormones / Q000096:biosynthesis* / Q000235:genetics; D007031:Hypothalamus / Q000254:growth & development* / Q000378:metabolism*; D059648:Kisspeptins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D011323:Primates
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C452848:DMXL2 protein, human; D007028:Hypothalamic Hormones; C106628:KISS1 protein, human; D059648:Kisspeptins; D009419:Nerve Tissue Proteins; C000588859:RFamide-related peptide-3, rat
keywords: DMXL2; GnIH; GnRH; Hypothalamus; Kiss1r; Kisspeptin; Marmoset; Non-human primate; Puberty