Prostaglandin E2 as a regulator of germ cells during ovarian development.
BACKGROUND
The formation of primordial follicles occurs during fetal life yet is critical to the determination of adult female fertility. Prior to this stage, germ cells proliferate, enter meiosis, and associate with somatic cells. Growth and survival factors implicated in these processes include activin A (INHBA), the neurotrophins BDNF and NT4 (NTF5), and MCL1. The prostaglandins have pleiotrophic roles in reproduction, notably in ovulation and implantation, but there are no data regarding roles for prostaglandins in human fetal ovarian development.


OBJECTIVE
The aim of the study was to investigate a possible role for prostaglandin (PG) E(2) in human fetal ovary development.


METHODS
In vitro analysis of ovarian development between 8 and 20 wk gestation was performed.


METHODS
The expression patterns of PG synthesis enzymes and the PGE(2) receptors EP2 and EP4 in the ovary were assessed, and downstream effects of PGE(2) on gene expression were analyzed.


RESULTS
Ovarian germ cells express the PG synthetic enzymes COX2 and PTGES as well as the EP2 and EP4 receptors, whereas COX1 is expressed by ovarian somatic cells. Treatment in vitro with PGE(2) increased the expression of BDNF mRNA 1.7 +/- 0.16-fold (P = 0.004); INHBA mRNA, 2.1 +/- 0.51-fold (P = 0.04); and MCL1 mRNA, 1.15 +/- 0.06-fold (P = 0.04), but not that of OCT4, DAZL, VASA, NTF5, or SMAD3.


CONCLUSIONS
These data indicate novel roles for PGE(2) in the regulation of germ cell development in the human ovary and show that these effects may be mediated by the regulation of factors including BDNF, activin A, and MCL1.
Bayne
Rosemary A L
RA
Medical Research Council Human Reproductive Sciences Unit, University of Edinburgh Centre for Reproductive Biology, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom. r.bayne@hrsu.mrc.ac.uk
Eddie
Sharon L
SL
Collins
Craig S
CS
Childs
Andrew J
AJ
Jabbour
Henry N
HN
Anderson
Richard A
RA
D028341:Activins / Q000378:metabolism; D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009865:Oocytes / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism*; D010053:Ovary / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism*; D011247:Pregnancy; D000071876:Prostaglandin-E Synthases; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019208:Brain-Derived Neurotrophic Factor; D064549:Myeloid Cell Leukemia Sequence 1 Protein; C545644:PTGER2 protein, human; C545650:PTGER4 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; C422405:activin A; D028341:Activins; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone