Transition Metal Chelator Induces Progesterone Production in Mouse Cumulus-Oocyte Complexes and Corpora Lutea.
Progesterone production is upregulated in granulosa cells (cumulus and mural) after the LH surge, but the intra-follicular mechanisms regulating this transition are not completely known. Recent findings show that the transition metal chelator, N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN), impairs ovarian function. In this study, we provide evidence that chelating transition metals, including zinc, enhances progesterone production. The findings show that TPEN (transition metal chelator) increases abundance of Cyp11a1 and Star messenger RNA (mRNA) between 8- and 20-fold and progesterone production more than 3-fold in cultured cumulus-oocyte complexes (COC). Feeding a zinc-deficient diet for 10 days, but not 3 days, increased Star, Hsd3b, and prostaglandin F2 alpha receptor (Ptgfr) mRNA ~2.5-fold, suggesting that the effect of TPEN is through modulation of zinc availability. Progesterone from cumulus cells promotes oocyte developmental potential. Blocking progesterone production with epostane during maturation reduced subsequent blastocyst formation from 89 % in control to 18 % in epostane-treated complexes, but supplementation with progesterone restored blastocyst developmental potential to 94 %. Feeding a zinc-deficient diet for 5 days before ovulation did not affect the number of CL, STAR protein, or serum progesterone. However, incubating luteal tissue with TPEN increased abundance of Star, Hsd3b, and Ptgfr mRNA 2-3-fold and increased progesterone production 3-fold. TPEN is known to abolish SMAD2/3 signaling in cumulus cells. However, treatment of COC with the SMAD2/3 phosphorylation inhibitor, SB421542, did not by itself induce steroidogenic transcripts but did potentiate EGF-induced Star mRNA expression. Collectively, the results show that depletion of transition metals with TPEN acutely enhances progesterone biosynthesis in COC and luteal tissue.
Center for Reproductive Biology and Health and Department of Animal Science, Pennsylvania State University, 206 Henning Building, University Park, PA, 16802, USA.|Department of Radiation Oncology, University of North Carolina at Chapel Hill, 2236 Marsico Hall, 125 Mason Farm Road, Chapel Hill, NC, 27599, USA.
X
X
Tian
Center for Reproductive Biology and Health and Department of Animal Science, Pennsylvania State University, 206 Henning Building, University Park, PA, 16802, USA.
K
K
Anthony
Center for Reproductive Biology and Health and Department of Animal Science, Pennsylvania State University, 206 Henning Building, University Park, PA, 16802, USA. fjd10@psu.edu.
Francisco J
FJ
Diaz
D000818:Animals; D002478:Cells, Cultured; D002614:Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003338:Corpus Luteum / Q000187:drug effects* / Q000378:metabolism*; D054885:Cumulus Cells / Q000187:drug effects* / Q000378:metabolism*; D004032:Diet; D005260:Female; D051379:Mice; D011374:Progesterone / Q000096:biosynthesis*; D015032:Zinc / Q000008:administration & dosage / Q000172:deficiency / Q000494:pharmacology*
D002614:Chelating Agents; D011374:Progesterone; D015032:Zinc
Ovary; Progesterone; TPEN