Abstract
ContextThe H19 long noncoding RNA (lncRNA) belongs to a highly conserved, imprinted gene cluster involved in embryonic development and growth control. We previously described a novel mechanism whereby the Anti-mullerian hormone (Amh) appears to be regulated by H19. However, the relationship between circulating H19 and markers of ovarian reserve including AMH not been investigated.ObjectiveTo determine whether H19 expression is altered in women with decreased ovarian reserve.DesignExperimental study.SettingYale School of Medicine (New Haven, USA) and Gazi University School of Medicine (Ankara, Turkey).Patients or other participantsA total of 141 women undergoing infertility evaluation and treatment.InterventionCollection of discarded blood samples and cumulus cells at the time of baseline infertility evaluation and transvaginal oocyte retrieval, respectively.Main outcome measureSerum and cumulus cell H19 expression.ResultsWomen with diminished ovarian reserve (as determined by AMH) had significantly lower serum H19 expression levels as compared to controls (p < 0.01). Serum H19 was moderately positively correlated with serum AMH. H19 expression was increased 3.7-fold in cumulus cells of IVF patients who demonstrated a high response to gonadotropins, compared to low responders (p < 0.05).ConclusionIn this study, we show that downregulation of H19 in serum and cumulus cells is closely associated with decreased ovarian reserve, as measured by decreased AMH levels and reduced oocyte yield at oocyte retrieval. Further study with expanded sample sizes is necessary to determine whether H19 may be of use as a novel biomarker for diminished ovarian reserve.
Highlights
The problem of ovarian aging has considerable impact on public health, and presently no viable preventative or treatment options are available
In this study, we show that downregulation of H19 in serum and cumulus cells is closely associated with decreased ovarian reserve, as measured by decreased anti-Mullerian hormone (AMH) levels and reduced oocyte yield at oocyte retrieval
H19 expression in cumulus cells H19 expression was significantly decreased (4.6 fold) in cumulus cells of in vitro fertilization (IVF) patients who demonstrated a poor response to gonadotropins compared to high responders (Fig. 2, p < 0.05)
Summary
The problem of ovarian aging has considerable impact on public health, and presently no viable preventative or treatment options are available. A drastic decline in the quantity of follicles and oocytes (the “ovarian reserve”), occurs [1], leading to decreased female fecundity and infertility. Historical data, as well as studies of women undergoing fertility treatment, have shown that female fertility begins to decline as early as age 30 [2, 3]. In 2014, over 30% of first births occurred in women over 30 [4]. Adding to the complexity of this challenge is the fact that fecundity varies even among women of similar age groups [6], and some women experience idiopathic accelerated follicle loss and early menopause. Why follicle growth and development go so drastically awry in some women is poorly understood, and many gaps remain in our understanding of the processes regulating the recruitment and growth of ovarian follicles
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