Involvement of the KIT/KITL signaling pathway in 4-vinylcyclohexene diepoxide-induced ovarian follicle loss in rats

Shannon M. Fernandez, Aileen F. Keating, Patricia J. Christian, Nivedita Sen, James B. Hoying, Heddwen L Brooks, Patricia B Hoyer

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Repeated daily dosing of rats with the occupational chemical 4-vinylcyclohexene diepoxide (VCD) depletes the ovary of primordial and primary follicles through an increase in the natural process of atresia. Additionally, in vitro exposure of Postnatal Day 4 (PND 4) rat ovaries to VCD causes similar follicular depletion. This study was designed to investigate survival signaling pathways that may be associated with VCD-induced ovotoxicity in small preantral follicles. Female Fischer 344 rats (PND 28) were dosed daily (80 mg/kg/day VCD i.p.; 12 days in vivo), and PND 4 ovaries were cultured (VCD 20 or 30 μM; 8 days in vitro). Microarray analysis identified a subset of 14 genes whose expression was increased or decreased by VCD in both experiments (i.e., via both exposure routes). Particularly, the analysis showed that relative to controls, VCD did not affect mRNA expression of growth and differentiation factor 9 (Gdf9), whereas there were decreases in mRNA encoding bone morphogenic protein receptor 1a (Bmpr1a) and Kit. To confirm findings from microarray, the genes Gdf9, Bmpr1a, and Kit were further examined. When growth factors associated with these pathways were added to ovarian cultures during VCD exposure, GDF9 and BMP4 had no effect on VCD-induced ovotoxicity; however, KITL attenuated this follicle loss. Additionally, there was a decrease in Kit and an increase in Kitl expression (mRNA and protein) following VCD exposure, relative to control. These results support that VCD compromises KIT/KITL signaling, which is critical for follicular survival in primordial and primary follicles.

Original languageEnglish (US)
Pages (from-to)318-327
Number of pages10
JournalBiology of Reproduction
Volume79
Issue number2
DOIs
StatePublished - Aug 2008

Fingerprint

Ovarian Follicle
Growth Differentiation Factor 9
Ovary
Messenger RNA
4-vinyl-1-cyclohexene dioxide
Bone and Bones
Proteins
Population Growth
Inbred F344 Rats
Microarray Analysis
Intercellular Signaling Peptides and Proteins
Gene Expression

Keywords

  • Kit
  • Kitl
  • Ovary
  • Ovotoxicity
  • Preantral follicles

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Embryology

Cite this

Involvement of the KIT/KITL signaling pathway in 4-vinylcyclohexene diepoxide-induced ovarian follicle loss in rats. / Fernandez, Shannon M.; Keating, Aileen F.; Christian, Patricia J.; Sen, Nivedita; Hoying, James B.; Brooks, Heddwen L; Hoyer, Patricia B.

In: Biology of Reproduction, Vol. 79, No. 2, 08.2008, p. 318-327.

Research output: Contribution to journalArticle

Fernandez, Shannon M. ; Keating, Aileen F. ; Christian, Patricia J. ; Sen, Nivedita ; Hoying, James B. ; Brooks, Heddwen L ; Hoyer, Patricia B. / Involvement of the KIT/KITL signaling pathway in 4-vinylcyclohexene diepoxide-induced ovarian follicle loss in rats. In: Biology of Reproduction. 2008 ; Vol. 79, No. 2. pp. 318-327.
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