Transcriptome profiling of kisspeptin neurons from the mouse arcuate nucleus reveals new mechanisms in estrogenic control of fertility.
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 119 (2022-07-05), Heft 27, S. 1-25
Online
academicJournal
Zugriff:
Kisspeptin neurons in the mediobasal hypothalamus (MBH) are critical targets of ovarian estrogen feedback regulating mammalian fertility. To reveal molecular mechanisms underlying this signaling, we thoroughly characterized the estrogen-regulated transcriptome of kisspeptin cells from ovariectomized transgenic mice substituted with 17β-estradiol or vehicle. MBH kisspeptin neurons were harvested using laser-capture microdissection, pooled, and subjected to RNA sequencing. Estrogen treatment significantly (p.adj. < 0.05) up-regulated 1,190 and down-regulated 1,139 transcripts, including transcription factors, neuropeptides, ribosomal and mitochondrial proteins, ion channels, transporters, receptors, and regulatory RNAs. Reduced expression of the excitatory serotonin receptor-4 transcript (Htr4) diminished kisspeptin neuron responsiveness to serotonergic stimulation. Many estrogen-regulated transcripts have been implicated in puberty/fertility disorders. Patients (n = 337) with congenital hypogonadotropic hypogonadism (CHH) showed enrichment of rare variants in putative CHH-candidate genes (e.g., LRP1B, CACNA1G, FNDC3A). Comprehensive characterization of the estrogen-dependent kisspeptin neuron transcriptome sheds light on the molecular mechanisms of ovary-brain communication and informs genetic research on human fertility disorders. [ABSTRACT FROM AUTHOR]
Titel: |
Transcriptome profiling of kisspeptin neurons from the mouse arcuate nucleus reveals new mechanisms in estrogenic control of fertility.
|
---|---|
Autor/in / Beteiligte Person: | Göcz, Balázs ; Rumpler, Éva ; Sárvári, Miklós ; Skrapits, Katalin ; Takács, Szabolcs ; Farkas, Imre ; Csillag, Veronika ; Trinh, Sarolta H. ; Bardóczi, Zsuzsanna ; Ruska, Yvette ; Solymosi, Norbert ; Póliska, Szilárd ; Szőke, Zsuzsanna ; Bartoloni, Lucia ; Zouaghi, Yassine ; Messina, Andrea ; Pitteloud, Nelly ; Anderson, Ross C. ; Millar, Robert P. ; Quinton, Richard |
Link: | |
Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 119 (2022-07-05), Heft 27, S. 1-25 |
Veröffentlichung: | 2022 |
Medientyp: | academicJournal |
ISSN: | 0027-8424 (print) |
DOI: | 10.1073/pnas.2113749119 |
Schlagwort: |
|
Sonstiges: |
|