title: Negative fetal FSH/LH regulation in late pregnancy is associated with declined kisspeptin/KISS1R expression in the tuberal hypothalamus.
abstract: OBJECTIVE
  Kisspeptins were recently identified as hypothalamic neuropeptides that control GnRH release at pubertal onset and in adults via the activation of KISS-1 receptor (KISS1R). Here, we have tested whether the fetal activation of the gonadotropic axis is related to the hypothalamic expression of kisspeptins and KISS1R.
  
  
  METHODS
  LH and FSH levels were measured in fetal blood from the 15th week of gestation (WG) to birth. Immunohistochemistry was performed on the hypothalamus and pituitary at different developmental stages.
  
  
  RESULTS
  Immunostaining for kisspeptins and KISS1R appeared for both proteins in the hypothalamus as early as 15 WG and subsequently increased until 30-31 WG. In the meantime, serum LH and FSH levels decreased from postmenopausal levels in females or adult levels in males to very low levels. At full term, kisspeptin and KISS1R staining was still observed in the paraventricular, supraoptic, and ventromedial hypothalamic nuclei but not in the arcuate nucleus or median eminence. Hypothalamic GnRH staining was observed at 15 WG and did not vary after the first trimester. In an arhinencephalic fetus of 23 WG, very few GnRH neurons were observed in the hypothalamus, but serum FSH and LH levels were postmenopausal.
  
  
  CONCLUSIONS
  Serum LH and FSH levels are independent from GnRH and kisspeptins at midgestation, and then GnRH progressively controls LH and FSH release. A shift from kisspeptin-independent to kisspeptin-dependent GnRH-induced LH and FSH release seems to occur after 30-31 WG. In addition to their function in adults, kisspeptins are also the master regulators of the gonadotropic axis activation in the fetus.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 676, F-75739 Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Guimiot
authors.forename: Lucie
authors.initials: L
authors.lastname: Chevrier
authors.forename: Sophie
authors.initials: S
authors.lastname: Dreux
authors.forename: Didier
authors.initials: D
authors.lastname: Chevenne
authors.forename: Alain
authors.initials: A
authors.lastname: Caraty
authors.forename: Anne Lise
authors.initials: AL
authors.lastname: Delezoide
authors.forename: Nicolas
authors.initials: N
authors.lastname: de Roux
mesh_terms: D001344:Autopsy; D015536:Down-Regulation; D005260:Female; D005312:Fetal Blood / Q000737:chemistry / Q000378:metabolism; D005333:Fetus / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism*; D005865:Gestational Age; D057809:HEK293 Cells; D006801:Humans; D007031:Hypothalamus / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D059648:Kisspeptins / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000097:blood / Q000378:metabolism*; D011263:Pregnancy Trimester, Third / Q000097:blood / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D000074502:Receptors, Kisspeptin-1
chemical_list: C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone