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Prostaglandin E₂ as a Regulator of Germ Cells during Ovarian Development

Medical Research Council Human Reproductive Sciences Unit (R.A.L.B., C.S.C., A.J.C., H.N.J.), and Division of Reproductive and Developmental Sciences (S.L.E., R.A.A.), University of Edinburgh Centre for Reproductive Biology, The Queen’s Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom

Address all correspondence and requests for reprints to: Dr. Rosemary A. L. Bayne, Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom. E-mail: r.bayne{at}hrsu.mrc.ac.uk.

Context: 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) E₂ in human fetal ovary development.

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

Main Outcome Measure(s): The expression patterns of PG synthesis enzymes and the PGE₂ receptors EP2 and EP4 in the ovary were assessed, and downstream effects of PGE₂ 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 PGE₂ 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 PGE₂ 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.