Abstract:
:Women with polycystic ovary syndrome (PCOS) and hyperandrogenism have altered hormone levels and suffer from ovarian dysfunction leading to subfertility. We have attempted to generate a model of hyperandrogenism by feeding mice chow supplemented with dehydroepiandrosterone (DHEA), an androgen precursor that is often elevated in women with PCOS. Treated mice had polycystic ovaries, low ovulation rates, disrupted estrous cycles, and altered hormone levels. Because DHEA is an inhibitor of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme in the pentose phosphate pathway, we tested the hypothesis that oocytes from DHEA-exposed mice would have metabolic disruptions. Citrate levels, glucose-6-phosphate dehydrogenase activity, and lipid content in denuded oocytes from these mice were significantly lower than controls, suggesting abnormal tricarboxylic acid and pentose phosphate pathway metabolism. The lipid and citrate effects were reversible by supplementation with nicotinic acid, a precursor for reduced nicotinamide adenine dinucleotide phosphate. These findings suggest that elevations in systemic DHEA can have a negative impact on oocyte metabolism and may contribute to poor pregnancy outcomes in women with hyperandrogenism and PCOS.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Jimenez PT,Frolova AI,Chi MM,Grindler NM,Willcockson AR,Reynolds KA,Zhao Q,Moley KHdoi
10.1210/en.2012-2140subject
Has Abstractpub_date
2013-12-01 00:00:00pages
4835-44issue
12eissn
0013-7227issn
1945-7170pii
en.2012-2140journal_volume
154pub_type
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