Distribution and responsiveness of rat anti-Müllerian hormone during ovarian development and VCD-induced ovotoxicity

Connie J. Mark-Kappeler, Nivedita Sen, Aileen F. Keating, I. Glenn Sipes, Patricia B Hoyer

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Anti-Müllerian hormone (AMH) is produced by granulosa cells in primary to small antral follicles of the adult ovary and helps maintain primordial follicles in a dormant state. The industrial chemical, 4-vinylcyclohexene diepoxide (VCD) causes specific ovotoxicity in primordial and small primary follicles of mice and rats. Previous studies suggest that this ovotoxicity involves acceleration of primordial to primary follicle recruitment via interactions with the Kit/Kit ligand signaling pathway. Because of its accepted role in inhibiting primordial follicle recruitment, the present study was designed to investigate a possible interaction between AMH and VCD-induced ovotoxicity. Protein distribution of AMH was compared in neonatal and adult F344 rat ovaries. AMH protein was visualized by immunofluorescence microscopy in large primary and secondary follicles of the adult ovary, but in small primary follicles in neonatal rat ovaries. In cultured postnatal day (PND) 4 F344 rat ovaries, VCD exposure (30μM, 2-8. days) decreased (P<0.05) AMH mRNA (d4-8) and protein (d6-8). Recombinant AMH (100-400 mg/ml) in PND4 ovaries cultured 8. days ± VCD (30μM) caused an increase (P<0.05) in primordial, and a decrease (P<0.05) in small primary follicles, supporting that AMH retarded primordial follicle recruitment. However, no concentration of AMH had an effect on VCD-induced ovotoxicity. Whereas, VCD caused a reduction in expression of AMH (d4-d8), it followed previously reported initial disruptions in Kit signaling induced by VCD (d2). Thus, collectively, these results do not support a mechanism whereby VCD causes ovotoxicity via generalized activation of primordial follicle recruitment, but instead provide further support for the specificity of other intracellular mechanisms involved in VCD-induced ovotoxicity.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalToxicology and Applied Pharmacology
Volume249
Issue number1
DOIs
StatePublished - Nov 15 2010

Fingerprint

Rats
Hormones
Ovary
Inbred F344 Rats
Industrial chemicals
4-vinyl-1-cyclohexene dioxide
Proteins
Stem Cell Factor
Granulosa Cells
Fluorescence Microscopy
Microscopic examination
Chemical activation
Messenger RNA

Keywords

  • 4-vinylcyclohexene diepoxide
  • Anti-Müllerian hormone
  • Follicle
  • Müllerian inhibiting substance
  • Ovary

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology
  • Medicine(all)

Cite this

Distribution and responsiveness of rat anti-Müllerian hormone during ovarian development and VCD-induced ovotoxicity. / Mark-Kappeler, Connie J.; Sen, Nivedita; Keating, Aileen F.; Sipes, I. Glenn; Hoyer, Patricia B.

In: Toxicology and Applied Pharmacology, Vol. 249, No. 1, 15.11.2010, p. 1-7.

Research output: Contribution to journalArticle

Mark-Kappeler, Connie J. ; Sen, Nivedita ; Keating, Aileen F. ; Sipes, I. Glenn ; Hoyer, Patricia B. / Distribution and responsiveness of rat anti-Müllerian hormone during ovarian development and VCD-induced ovotoxicity. In: Toxicology and Applied Pharmacology. 2010 ; Vol. 249, No. 1. pp. 1-7.
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