PMID- 31141131
OWN - NLM
STAT- MEDLINE
DCOM- 20200929
LR  - 20200929
IS  - 1529-7268 (Electronic)
IS  - 0006-3363 (Print)
IS  - 0006-3363 (Linking)
VI  - 101
IP  - 2
DP  - 2019 Aug 1
TI  - Mice lacking membrane estrogen receptor 1 are protected from reproductive 
      pathologies resulting from developmental estrogen exposuredagger.
PG  - 392-404
LID - 10.1093/biolre/ioz090 [doi]
AB  - Both membrane and nuclear fractions of estrogen receptor 1 (ESR1) mediate 
      17beta-estradiol (E2) actions. Mice expressing nuclear (n)ESR1 but lacking membrane 
      (m)ESR1 (nuclear-only estrogen receptor 1 [NOER] mice) show reduced E2 
      responsivity and reproductive abnormalities culminating in adult male and female 
      infertility. Using this model, we investigated whether reproductive pathologies 
      caused by the synthetic estrogen diethylstilbestrol (DES) are mitigated by mESR1 
      ablation. Homozygous and heterozygous wild-type (WT and HET, respectively) and 
      NOER male and female mice were subcutaneously injected with DES (1 mg/kg body 
      weight [BW]) or vehicle daily from postnatal day (PND) 1-5. Uterine histology was 
      assessed in select DES-treated females at PND 5, whereas others were 
      ovariectomized at PND 60 and treated with E2 (10 mug/kg BW) or vehicle 2 weeks 
      later. Neonatal DES exposure resulted in ovary-independent epithelial 
      proliferation in the vagina and uterus of WT but not NOER females. Neonatal DES 
      treatment also induced ovary-independent adult expression of classical E2-induced 
      transcripts (e.g., lactoferrin [Ltf] and enhancer of zeste homolog 2 [Ezh2]) in 
      WT but not NOER mice. At PND 90, DES-treated WT and HET males showed smaller 
      testes and a high incidence of bacterial pyogranulomatous inflammation 
      encompassing the testes, epididymis and occasionally the ductus deferens with 
      spread to lumbar lymph nodes; such changes were largely absent in NOER males. 
      Results indicate that male and female NOER mice are protected from deleterious 
      effects of neonatal DES, and thus mESR1 signaling is required for adult 
      manifestation of DES-induced reproductive pathologies in both sexes.
CI  - (c) The Author(s) 2019. Published by Oxford University Press on behalf of Society 
      for the Study of Reproduction.
FAU - Nanjappa, Manjunatha K
AU  - Nanjappa MK
AD  - Department of Physiological Sciences, University of Florida, Gainesville, 
      Florida, USA.
FAU - Medrano, Theresa I
AU  - Medrano TI
AD  - Department of Physiological Sciences, University of Florida, Gainesville, 
      Florida, USA.
FAU - Mesa, Ana M
AU  - Mesa AM
AD  - Department of Physiological Sciences, University of Florida, Gainesville, 
      Florida, USA.
FAU - Ortega, Madison T
AU  - Ortega MT
AD  - Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA.
AD  - Biomedical Sciences, University of Missouri, Columbia, Missouri, USA.
FAU - Caldo, Paul D
AU  - Caldo PD
AD  - Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA.
AD  - Biomedical Sciences, University of Missouri, Columbia, Missouri, USA.
FAU - Mao, Jiude
AU  - Mao J
AD  - Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA.
AD  - Biomedical Sciences, University of Missouri, Columbia, Missouri, USA.
FAU - Kinkade, Jessica A
AU  - Kinkade JA
AD  - Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA.
AD  - Biomedical Sciences, University of Missouri, Columbia, Missouri, USA.
FAU - Levin, Ellis R
AU  - Levin ER
AD  - Division of Endocrinology, Department of Medicine, University of California, 
      Irvine, Irvine, California, USA.
AD  - Department of Veterans Affairs Medical Center, Long Beach, Long Beach, 
      California, USA.
FAU - Rosenfeld, Cheryl S
AU  - Rosenfeld CS
AD  - Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA.
AD  - Biomedical Sciences, University of Missouri, Columbia, Missouri, USA.
AD  - Thompson Center for Autism and Neurobehavioral Disorders, University of Missouri, 
      Columbia, Missouri, USA.
AD  - MU Informatics Institute, University of Missouri, Columbia, Missouri, USA.
FAU - Cooke, Paul S
AU  - Cooke PS
AD  - Department of Physiological Sciences, University of Florida, Gainesville, 
      Florida, USA.
LA  - eng
GR  - R01 ES025547/ES/NIEHS NIH HHS/United States
GR  - R03 HD087528/HD/NICHD NIH HHS/United States
GR  - R21 HD088006/HD/NICHD NIH HHS/United States
GR  - R25 GM056901/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogens, Non-Steroidal)
RN  - 0 (RNA, Messenger)
RN  - 731DCA35BT (Diethylstilbestrol)
SB  - IM
MH  - Animals
MH  - Diethylstilbestrol/*toxicity
MH  - Estrogen Receptor alpha/*genetics
MH  - Estrogens, Non-Steroidal/*toxicity
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Genital Diseases, Male/chemically induced
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Knockout
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - RNA, Messenger/genetics/metabolism
MH  - Uterus/metabolism
PMC - PMC6736026
OTO - NOTNLM
OT  - epididymis
OT  - estrogen
OT  - steroid receptors
OT  - testis
OT  - uterus
OT  - vagina
OT  - xenoestrogens
EDAT- 2019/05/30 06:00
MHDA- 2020/09/30 06:00
PMCR- 2020/08/01
CRDT- 2019/05/30 06:00
PHST- 2019/01/25 00:00 [received]
PHST- 2019/03/22 00:00 [revised]
PHST- 2019/05/30 06:00 [pubmed]
PHST- 2020/09/30 06:00 [medline]
PHST- 2019/05/30 06:00 [entrez]
PHST- 2020/08/01 00:00 [pmc-release]
AID - 5505824 [pii]
AID - ioz090 [pii]
AID - 10.1093/biolre/ioz090 [doi]
PST - ppublish
SO  - Biol Reprod. 2019 Aug 1;101(2):392-404. doi: 10.1093/biolre/ioz090.