Abstract
BackgroundThe link between reproductive life history and incidence of ovarian tumors is well known. Periods of reduced ovulations may confer protection against ovarian cancer. Using phenotypic data available for mouse, a possible association between the ovarian transcriptome, reproductive records and spontaneous ovarian tumor rates was investigated in four mouse inbred strains. NIA15k-DNA microarrays were employed to obtain expression profiles of BalbC, C57BL6, FVB and SWR adult ovaries.ResultsLinear regression analysis with multiple-test control (adjusted p ≤ 0.05) resulted in ovarian tumor frequency (OTF) and number of litters (NL) as the top-correlated among five tested phenotypes. Moreover, nearly one-hundred genes were coincident between these two traits and were decomposed in 76 OTF(–) NL(+) and 20 OTF(+) NL(–) genes, where the plus/minus signs indicate the direction of correlation. Enriched functional categories were RNA-binding/mRNA-processing and protein folding in the OTF(–) NL(+) and the OTF(+) NL(–) subsets, respectively. In contrast, no associations were detected between OTF and litter size (LS), the latter a measure of ovulation events in a single estrous cycle.ConclusionLiterature text-mining pointed to post-transcriptional control of ovarian processes including oocyte maturation, folliculogenesis and angiogenesis as possible causal relationships of observed tumor and reproductive phenotypes. We speculate that repetitive cycling instead of repetitive ovulations represent the actual link between ovarian tumorigenesis and reproductive records.
Highlights
The link between reproductive life history and incidence of ovarian tumors is well known
Epidemiological evidence indicates that multiparity and breastfeeding as well as endocrine disrupting agents used in oral contraception, hormone replacement therapy and infertility treatment- modulate the risk of ovarian cancer [1]
In an attempt to gain novel information linking reproductive parameters with ovarian tumorigenesis we describe here a correlation analysis between spontaneous ovarian tumors, reproductive phenotypes and gene expression profiles obtained with NIA15k-DNA microarrays from ovaries of four mouse inbred strains
Summary
The link between reproductive life history and incidence of ovarian tumors is well known. Periods of reduced ovulations may confer protection against ovarian cancer. The laboratory mouse has been increasingly used to model several aspects of ovarian cancer [4]. The length of estrous cycles increases while the monthly cycle frequency decreases in ageing mice [6]. The number of ovulations roughly reaches 500 during the reproductive life of women while in mice this number can be achieved earlier than middle age due to multiple ovulations in a single cycle [7] as judged by the litter size observed in mice [5]. Invaginations and cell layering are common observations in the mouse and human ovaries [7]
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