Sphingosine 1-phosphate (S1P), an inflammatory mediator, is abundantly contained in red blood cells and platelets. We hypothesized that the S1P concentration in the peritoneal cavity would increase especially during the menstrual phase due to the reflux of menstrual blood, and investigated the S1P concentration in the human peritoneal fluid (PF) from 14 non-endometriosis and 19 endometriosis patients. Although the relatively small number of samples requires caution in interpreting the results, S1P concentration in the PF during the menstrual phase was predominantly increased compared to the non-menstrual phase, regardless of the presence or absence of endometriosis. During the non-menstrual phase, patients with endometriosis showed a significant increase in S1P concentration compared to controls. In vitro experiments using human intra-peritoneal macrophages (MΦ) showed that S1P stimulation biased them toward an M2MΦ-dominant condition and increased the expression of IL-6 and COX-2. An in vivo study showed that administration of S1P increased the size of the endometriotic-like lesion in a mouse model of endometriosis.

The presence of human progesterone receptor (PR) mRNA variants has been demonstrated in uterine endometrium and breast tissues as well as in cancer cells of these tissues. While exon deletions by the alternative splicing in these variants have been reported, there are few reports available on the PR mRNA variants with exon insertion. In the present study, we attempted to detect a PR mRNA variant containing the exon insertions in normal uterine endometrium. Endometrial tissues were subjected to reverse transcription-polymerase chain reaction (RT-PCR) with PCR primers which were located in exons 3 and 8. Analysis of the RT-PCR products revealed the presence of a novel PR mRNA variant which contained a 232 bp inserted nucleotide sequence between exons 4 and 5. We termed this transcript the “i45 PR mRNA variant”. Genomic analysis indicated that the inserted sequence was derived from two novel independent exons of 123 bp and 109 bp, termed “exon i45a” and “exon i45b”, respectively, which are located between exons 4 and 5 of the human PR gene. The i45 PR mRNA variant was further detected in uterine endometrial cancer tissues as well as in the normal uterine endometrium. These results demonstrate the presence of a novel PR mRNA variant with exon insertions in the human tissue for the first time. The i45 PR variant protein, possibly transcribed from this i45 PR mRNA variant, may play physiological and/or pathological roles in the human uterine endometrium.

Fetal cell microchimerism is defined as the persistence of pluripotent fetal cells in the maternal body long after delivery. The exact process by which fetal cells cross the placental barrier and e...