Effect of inhibition of sterol Δ14-reductase on accumulation of meiosis-activating sterol and meiotic resumption in cumulus-enclosed mouse oocytes in vitro

Lise Leonardsen, Maria Strømstedt, Ditte Jacobsen, Karina S. Kristensen, Mogens Baltsen, Claus Yding Andersen, Anne Grete Byskov

Research output: Contribution to journalJournal articleResearchpeer-review


Two sterols of the cholesterol biosynthetic pathway induce resumption of meiosis in mouse oocytes in vitro. The sterols, termed meiosis-activating sterols (MAS), have been isolated from human follicular fluid (FF-MAS, 4,4-dimethyl-5α-cholest-8,14,24-triene-3β-ol) and from bull testicular tissue (T-MAS, 4,4-dimethyl-5α-cholest-8,24-diene-3β-ol). FF-MAS is the first intermediate in the cholesterol biosynthesis from lanosterol and is converted to T-MAS by sterol Δ14-reductase. An inhibitor of Δ7-reductase and Δ14 reductase, AY9944-A-7, causes cells with a constitutive cholesterol biosynthesis to accumulate FF-MAS and possibly other intermediates between lanosterol and cholesterol. The aim of the present study was to evaluate whether AY9944-A-7 added to cultures of cumulus-oocyte complexes (COC) from mice resulted in accumulation of MAS and meiotic maturation. AY9944-A-7 stimulated dose dependently (5-25 μmol l -1) COC to resume meiosis when cultured for 22 h in α minimal essential medium (α-MEM) containing 4 mmol hypoxanthine l -1, a natural inhibitor of meiotic maturation. In contrast, naked oocytes were not induced to resume meiosis by AY9944-A-7. When cumulus cells were separated from their oocytes and co-cultured, AY9944-A-7 did not affect resumption of meiosis, indicating that intact oocyte-cumulus cell connections are important for AY9944-A-7 to exert its effect on meiosis. Cultures of COC with 10 μmol AY9944-A-7 l -1 in the presence of [ 3H]mevalonic acid, a natural precursor for steroid synthesis, resulted in accumulation of labelled FF-MAS, which had an 11-fold greater amount of radioactivity incorporated per COC compared with the control culture without AY9944-A-7. In contrast, incorporation of radioactivity into the cholesterol fraction was reduced 30-fold in extracts from the same oocytes. The present findings demonstrate for the first time that COC can synthesize cholesterol from mevalonate and accumulate FF-MAS in the presence of AY9944-A-7. Furthermore, AY9944-A-7 stimulated meiotic maturation dose dependently, indicating that FF-MAS, and possibly other sterol intermediates of the cholesterol synthesis pathway, play a central role in stimulating mouse oocytes to resume meiosis. The results also indicate that oocytes may not synthesize steroids from mevalonate.

Original languageEnglish
JournalJournal of Reproduction and Fertility
Issue number1
Pages (from-to)171-179
Number of pages9
Publication statusPublished - Jan 2000
Externally publishedYes


  • disease, health science and nursing


Dive into the research topics of 'Effect of inhibition of sterol Δ14-reductase on accumulation of meiosis-activating sterol and meiotic resumption in cumulus-enclosed mouse oocytes in vitro'. Together they form a unique fingerprint.

Cite this