Oral Presentation ESA-SRB Conference 2015

Regulation of Fibrillin Genes During Development of the Bovine and Human Ovary  (#91)

Nicole A Bastian 1 , Rosemary A Bayne 2 , Katja Hummitzsch 1 , Nick Hatzirodos 1 , Wendy M Bonner 1 , Monica D Hartanti 1 , Helen F Irving-Rodgers 3 , Richard A Anderson 2 , Ray J Rodgers 1
  1. Discipline of Obstetrics and Gynaecology, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia
  2. Medical Research Council Human Reproductive Sciences Unit and Division of Reproductive and Developmental Sciences, Centre for Reproductive Biology, University of Edinburgh, Edinburgh, United Kingdom
  3. School of Medical Science, Griffith University, Gold Coast Campus, Queensland, Australia

Fibrillins are extracellular matrix proteins that play important roles in regulating TGFβ activity. TGFβ stimulates fibroblasts, present in ovarian stromal compartments, to proliferate and synthesise collagen. Stromal expansion in the developing fetal ovary is crucial to ensure correct ovarian structural organisation and function. Expression of FBN3 has been associated with PCOS in women (JCEM, 2006. 91: 4112-7).  However, it is not expressed in the adult ovary, only in the stroma of the fetal ovary and only during the first trimester (FASEB J, 2011. 25: 2256-65). FBN1 is expressed at constant levels and at higher levels in the adult ovary (FASEB J, 2011. 25: 2256-65). We examined the expression of FBN1-3 in bovine and human fetal ovaries in vitro. Following 24 h of culture of collagenase-dispersed bovine fetal fibroblasts from the first trimester, the expression of FBN1 significantly increased but FBN2 and FBN3 significantly decreased.  When undispersed bovine fetal ovarian tissue was cultured, FBN1 expression remained unchanged, however expression of both FBN2 and FBN3 declined. TGFβ-1 decreased FBN1 and FBN2 expression only in bovine first trimester fibroblasts, but did not affect FBN3 expression. Additionally, human fetal (9-17 weeks gestational age) ovarian somatic cells were cultured over a number of passages. FBN1 and FBN2 expression increased whereas FBN3 expression drastically decreased. The cultured ovarian somatic cells were then treated with TGFβ-1 or SB431542. Interestingly, TGFβ-1 and SB431542 differentially regulated FBN1 and FBN2 expression in these somatic cells. Overall these results suggest that in vitro ovarian fibroblasts from fetal ovaries switch off FBN3 and switch on FBN1 as occurs in vivo during development.  Additionally the regulation of these genes changes over gestation. The mechanisms responsible are not known at this time. However, we have established a model system for the study of developmental changes in the ovarian somatic compartment.

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