PMID- 19442818 OWN - NLM STAT- MEDLINE DCOM- 20090804 LR - 20220408 IS - 1872-9711 (Electronic) IS - 0161-813X (Print) IS - 0161-813X (Linking) VI - 30 IP - 3 DP - 2009 May TI - Impact of neonatal exposure to the ERalpha agonist PPT, bisphenol-A or phytoestrogens on hypothalamic kisspeptin fiber density in male and female rats. PG - 350-7 LID - 10.1016/j.neuro.2009.02.010 [doi] AB - Neonatal exposure to endocrine disrupting compounds (EDCs) can impair reproductive physiology, but the specific mechanisms by which this occurs remain largely unknown. Growing evidence suggests that kisspeptin (KISS) neurons play a significant role in the regulation of pubertal onset and ovulation, therefore disruption of KISS signaling could be a mechanism by which EDCs impair reproductive maturation and function. We have previously demonstrated that neonatal exposure to phytoestrogens decreases KISS fiber density in the anterior hypothalamus of female rats, an effect which was associated with early persistent estrus and the impaired activation gonadotropin releasing hormone (GnRH) neurons. The goals of the present study were to (1) determine if an ERalpha selective agonist (PPT) or bisphenol-A (BPA) could produce similar effects on hypothalamic KISS content in female rats and (2) to determine if male KISS fiber density was also vulnerable to disruption by EDCs. We first examined the effects of neonatal exposure to PPT, a low (50 microg/kg bw) BPA dose, and a high (50 mg/kg bw) BPA dose on KISS immunoreactivity (-ir) in the anterior ventral periventricular (AVPV) and arcuate (ARC) nuclei of adult female rats, using estradiol benzoate (EB) and a sesame oil vehicle as controls. AVPV KISS-ir, following ovariectomy (OVX) and hormone priming, was significantly lower in the EB and PPT groups but not the BPA groups. ARC KISS-ir levels were significantly diminished in the EB and high dose BPA groups, and there was a nonsignificant trend for lower KISS-ir in the PPT group. We next examined effects of neonatal exposure to a low (50 microg/kg bw) dose of BPA and the phytoestrogens genistein (GEN) and equol (EQ) on KISS-ir in the AVPV and ARC of adult male rats, using OVX females as an additional control group. None of the compounds affected KISS-ir in the male hypothalamus. Our results suggest that the organization of hypothalamic KISS fibers may be vulnerable to disruption by EDC exposure and that females might be more sensitive than males. FAU - Patisaul, Heather B AU - Patisaul HB AD - Department of Biology, North Carolina State University, 127 David Clark Labs, Raleigh, NC 27695, USA. Heather_Patisaul@ncsu.edu FAU - Todd, Karina L AU - Todd KL FAU - Mickens, Jillian A AU - Mickens JA FAU - Adewale, Heather B AU - Adewale HB LA - eng GR - R01 ES016001/ES/NIEHS NIH HHS/United States GR - R01ES016001/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20090225 PL - Netherlands TA - Neurotoxicology JT - Neurotoxicology JID - 7905589 RN - 0 (Benzhydryl Compounds) RN - 0 (Estrogen Receptor alpha) RN - 0 (Kiss1 protein, rat) RN - 0 (Kisspeptins) RN - 0 (Phenols) RN - 0 (Phytoestrogens) RN - 0 (Proteins) RN - 0 (Pyrazoles) RN - 0T83Y6JZPF (4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol) RN - 1S4CJB5ZGN (estradiol 3-benzoate) RN - 4G7DS2Q64Y (Progesterone) RN - 4TI98Z838E (Estradiol) RN - MLT3645I99 (bisphenol A) SB - IM MH - Animals MH - *Animals, Newborn MH - Benzhydryl Compounds MH - Estradiol/analogs & derivatives/pharmacology MH - Estrogen Receptor alpha/*agonists MH - Female MH - Hypothalamus/*anatomy & histology MH - Kisspeptins MH - Male MH - Nerve Fibers/*drug effects/metabolism MH - Ovariectomy MH - Phenols/*pharmacology MH - Phytoestrogens/*pharmacology MH - Progesterone/pharmacology MH - Proteins/metabolism MH - Pyrazoles/*pharmacology MH - Rats MH - Rats, Long-Evans MH - *Sex Characteristics PMC - PMC3691558 MID - NIHMS479278 EDAT- 2009/05/16 09:00 MHDA- 2009/08/06 09:00 PMCR- 2013/06/25 CRDT- 2009/05/16 09:00 PHST- 2008/10/31 00:00 [received] PHST- 2009/02/11 00:00 [revised] PHST- 2009/02/13 00:00 [accepted] PHST- 2009/05/16 09:00 [entrez] PHST- 2009/05/16 09:00 [pubmed] PHST- 2009/08/06 09:00 [medline] PHST- 2013/06/25 00:00 [pmc-release] AID - S0161-813X(09)00050-3 [pii] AID - 10.1016/j.neuro.2009.02.010 [doi] PST - ppublish SO - Neurotoxicology. 2009 May;30(3):350-7. doi: 10.1016/j.neuro.2009.02.010. Epub 2009 Feb 25.