PMID- 28520915
OWN - NLM
STAT- MEDLINE
DCOM- 20180420
LR  - 20180420
IS  - 1529-7268 (Electronic)
IS  - 0006-3363 (Linking)
VI  - 96
IP  - 6
DP  - 2017 Jun 1
TI  - Ovary-specific depletion of the nuclear receptor Nr5a2 compromises expansion of 
      the cumulus oophorus but not fertilization by intracytoplasmic sperm injection.
PG  - 1231-1243
LID - 10.1093/biolre/iox045 [doi]
AB  - The orphan nuclear receptor, liver receptor homolog-1 (aka Nuclear receptor 
      subfamily 5, Group A, Member 2 (Nr5a2)), is widely expressed in mammalian 
      tissues, and its ovarian expression is restricted to granulosa cells of activated 
      follicles. We employed the floxed Nr5a2 (Nr5a2f/f) mutant mouse line and two 
      granulosa-specific Cre lines, Anti-Mullerian hormone receptor- 2 (Amhr2Cre) and 
      transgenic cytochrome P450 family 19 subfamily A polypeptide 1 (tgCyp19Cre), to 
      develop two tissue- and time-specific Nr5a2 depletion models: Nr5a2Amhr2-/- and 
      Nr5a2Cyp19-/-. In the Nr5a2Cyp19-/- ovaries, Nr5a2 was depleted in mural 
      granulosa, but not cumulus cells. We induced follicular development in mutant and 
      wild-type (control, CON) mice with equine chorionic gonadotropin followed 44 h 
      later treatment with human chorionic gonadotropin (hCG) to induce ovulation. Both 
      Nr5a2Amhr2-/- and Nr5a2Cyp19-/- cumulus-oocyte complexes underwent a reduced 
      degree of expansion in vitro relative to wild-type mice. We found downregulation 
      of epiregulin (Ereg), amphiregulin (Areg), betacellulin (Btc) and tumor necrosis 
      factor stimulated gene-6 (Tnfaip6) transcripts in Nr5a2Amhr2-/- and Nr5a2Cyp19-/- 
      ovaries. Tnfaip6 protein abundance, by quantitative immunofluorescence, was 
      likewise substantially reduced in the Nr5a2-depleted model. Transcript abundance 
      for connexin 43 (Gja1) in granulosa cells was lower at 0 h and maximum at 8 h 
      post-hCG in both Nr5a2Amhr2-/- and Nr5a2Cyp19-/- follicles, while Gja1 protein 
      was not different prior to the ovulatory signal, but elevated at 8 h in 
      Nr5a2Amhr2-/- and Nr5a2Cyp19-/- follicles. In both mutant genotypes, oocytes can 
      mature in vivo and resulting embryos were capable of proceeding to blastocyst 
      stagein vitro. We conclude that Nr5a2 is essential for cumulus expansion in 
      granulosa cells throughout follicular development. The disruption of Nr5a2 in 
      follicular somatic cells does not affect the capacity of the oocyte to be 
      fertilized by intracytoplasmic sperm injection.
CI  - (c) Crown copyright 2017.
FAU - Bertolin, Kalyne
AU  - Bertolin K
AD  - Centre de recherche en reproduction et fertilite, Faculte de medecine 
      veterinaire, Universite de Montreal, St-Hyacinthe, Quebec, Canada.
FAU - Meinsohn, Marie-Charlotte
AU  - Meinsohn MC
AD  - Centre de recherche en reproduction et fertilite, Faculte de medecine 
      veterinaire, Universite de Montreal, St-Hyacinthe, Quebec, Canada.
FAU - Suzuki, Joao
AU  - Suzuki J
AD  - Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, 
      Canada.
FAU - Gossen, Jan
AU  - Gossen J
AD  - Osteo Pharma BV, 5349 Oss, The Netherlands.
FAU - Schoonjans, Kristina
AU  - Schoonjans K
AD  - Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Federale de 
      Lausanne, Lausanne, Switzerland.
FAU - Duggavathi, Rajesha
AU  - Duggavathi R
AD  - Department of Animal Science, McGill University, Sainte-Anne-de-Bellevue, Quebec, 
      Canada.
FAU - Murphy, Bruce D
AU  - Murphy BD
AD  - Centre de recherche en reproduction et fertilite, Faculte de medecine 
      veterinaire, Universite de Montreal, St-Hyacinthe, Quebec, Canada.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (Connexin 43)
RN  - 0 (GJA1 protein, mouse)
RN  - 0 (Nr5a2 protein, mouse)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
SB  - IM
MH  - Animals
MH  - Connexin 43/genetics/metabolism
MH  - Cumulus Cells/*physiology
MH  - Estrous Cycle
MH  - Female
MH  - Fertilization/physiology
MH  - Gene Deletion
MH  - Gene Expression Regulation/physiology
MH  - Male
MH  - Mice
MH  - Oocytes/physiology
MH  - Ovary/drug effects/*physiology
MH  - Receptors, Cytoplasmic and Nuclear/genetics/*metabolism
MH  - Sperm Injections, Intracytoplasmic/*methods
OTO - NOTNLM
OT  - Nr5a2
OT  - conditional knockout mouse
OT  - cumulus expansion
OT  - fertilization
OT  - granulosa cells
EDAT- 2017/05/19 06:00
MHDA- 2018/04/21 06:00
CRDT- 2017/05/19 06:00
PHST- 2017/03/03 00:00 [received]
PHST- 2017/05/17 00:00 [accepted]
PHST- 2017/05/19 06:00 [pubmed]
PHST- 2018/04/21 06:00 [medline]
PHST- 2017/05/19 06:00 [entrez]
AID - 3831258 [pii]
AID - 10.1093/biolre/iox045 [doi]
PST - ppublish
SO  - Biol Reprod. 2017 Jun 1;96(6):1231-1243. doi: 10.1093/biolre/iox045.