PMID- 30920587
OWN - NLM
STAT- MEDLINE
DCOM- 20191216
LR  - 20191217
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Linking)
VI  - 160
IP  - 5
DP  - 2019 May 1
TI  - Neonatal Estrogen Causes Irreversible Male Infertility via Specific Suppressive 
      Action on Hypothalamic Kiss1 Neurons.
PG  - 1223-1233
LID - 10.1210/en.2018-00732 [doi]
AB  - Aberrant exposure to estrogen-like compounds during the critical developmental 
      period may cause improper hypothalamic programming, thus resulting in 
      reproductive dysfunction in adulthood in male mammals. Kisspeptin-neurokinin 
      B-dynorphin A (KNDy) neurons in the arcuate nucleus (ARC) have been suggested to 
      govern tonic GnRH/gonadotropin release to control reproduction in male mammals. 
      In this study, we report that chronic exposure to supraphysiological levels of 
      estrogen during the neonatal period caused an irreversible suppression of KNDy 
      genes in the ARC, resulting in reproductive dysfunction in male rats. Daily 
      estradiol benzoate (EB) administration from days 0 to 10 postpartum caused 
      smaller seminiferous tubules, abnormal spermatogenesis, and a decrease in plasma 
      testosterone in adult male rats. The neonatal EB treatment profoundly suppressed 
      LH pulse and ARC KNDy gene expression at adulthood, but it failed to affect the 
      number of GnRH gene-expressing cells in male rats. The EB treatment failed to 
      affect gene expression of other neuropeptides, such as GHRH, proopiomelanocortin, 
      and agouti-related protein in the ARC, suggesting that ARC KNDy neurons would be 
      a specific target of neonatal estrogen to cause male reproductive dysfunction. 
      Because LH secretory responses to kisspeptin challenge and GnRH expression were 
      spared in male rats with the EB treatment, LH pulse suppression is most probably 
      due to ARC KNDy deficiency. Taken together, the current study indicates that 
      chronic exposure to estrogenic chemicals in the developing brain causes a defect 
      of ARC KNDy neurons, resulting in an inhibition of pulsatile GnRH/LH release and 
      the failure of spermatogenesis and steroidogenesis.
CI  - Copyright (c) 2019 Endocrine Society.
FAU - Minabe, Shiori
AU  - Minabe S
AD  - Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo, Japan.
AD  - Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon 
      Medical School, Tokyo, Japan.
FAU - Sato, Marimo
AU  - Sato M
AD  - Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo, Japan.
FAU - Inoue, Naoko
AU  - Inoue N
AD  - Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 
      Japan.
FAU - Watanabe, Youki
AU  - Watanabe Y
AD  - Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon 
      Medical School, Tokyo, Japan.
FAU - Magata, Fumie
AU  - Magata F
AD  - Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo, Japan.
FAU - Matsuda, Fuko
AU  - Matsuda F
AD  - Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo, Japan.
FAU - Uenoyama, Yoshihisa
AU  - Uenoyama Y
AD  - Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 
      Japan.
FAU - Ozawa, Hitoshi
AU  - Ozawa H
AD  - Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon 
      Medical School, Tokyo, Japan.
FAU - Tsukamura, Hiroko
AU  - Tsukamura H
AD  - Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Kiss1 protein, rat)
RN  - 0 (Kisspeptins)
RN  - 1S4CJB5ZGN (estradiol 3-benzoate)
RN  - 3XMK78S47O (Testosterone)
RN  - 4TI98Z838E (Estradiol)
RN  - 74913-18-1 (Dynorphins)
RN  - 86933-75-7 (Neurokinin B)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Arcuate Nucleus of Hypothalamus/*drug effects/metabolism
MH  - Dynorphins/genetics/metabolism
MH  - Estradiol/administration & dosage/*analogs & derivatives/pharmacology
MH  - Gene Expression Regulation, Developmental/*drug effects
MH  - In Situ Hybridization
MH  - Infertility, Male/blood/*genetics
MH  - Kisspeptins/*genetics/metabolism
MH  - Male
MH  - Neurokinin B/genetics/metabolism
MH  - Neurons/*drug effects/metabolism
MH  - Rats, Wistar
MH  - Spermatogenesis/drug effects/genetics
MH  - Testosterone/blood
EDAT- 2019/03/29 06:00
MHDA- 2019/12/18 06:00
CRDT- 2019/03/29 06:00
PHST- 2018/08/28 00:00 [received]
PHST- 2019/03/21 00:00 [accepted]
PHST- 2019/03/29 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/03/29 06:00 [entrez]
AID - 5421007 [pii]
AID - 10.1210/en.2018-00732 [doi]
PST - ppublish
SO  - Endocrinology. 2019 May 1;160(5):1223-1233. doi: 10.1210/en.2018-00732.