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The objective of this study was to investigate how placental gene expression differs in two consecutive pregnancies in same sex siblings, and its possible association with the "maternal constraint" hypothesis. Material was gathered from the BASIC study (Biological, Affect, Stress, Imaging, and Cognition in Pregnancy and the Puerperium), a population based prospective study that was started in 2009 in Uppsala. Over 900 specimens of placenta biopsies were collected and out of these 10 women gave birth twice, to the same sex child, and were included in this study. The total RNA was isolated and prepared from frozen villous tissue from the placenta and further analyzed by use of Ion AmpliSeq Human Transcriptome Gene Expression kit. A total of 234 genes differed significantly between the first and second pregnancy placentas, when adjusting for delivery mode, maternal BMI and gestational age. Of special interest was the down-regulated group of genes in the second pregnancy. Exemplified by Pentraxin 3, SRY-Box Transcription Factor 9, and Serum Amyloid A1, which all were associated with biological processes involved in the immune system and inflammation. Further, protein-protein interaction analysis visualized them as hub genes interacting with several of the other differentially expressed genes. How these altered gene expressions affect maternal constraint during pregnancy needs further validation in lager study cohorts and also future validation in functional assays., De två första författarna delar förstaförfattarskapet.

Multiple studies have shown associations between exposure to endocrine disrupting chemicals (EDCs) and reduced fertility in women. However, little is known about the target organs of chemical disruption of female fertility. Here, we focus on the hormone-sensitive uterine lining, the endometrium, as a potential target. Decidualization is the morphological and functional change that endometrial stromal cells undergo to support endometrial receptivity, which is crucial for successful implantation, placentation, and pregnancy. We investigated the effect of nine selected EDCs on primary human endometrial stromal cell decidualization in vitro. The cells were exposed to a decidualization-inducing mixture in the presence or absence of 1 mu M of nine different EDCs for nine days. Extent of decidualization was assessed by measuring the activity of cAMP dependent protein kinase, Rho-associated coiled-coil containing protein kinase, and protein kinase B in lysates using photoluminescent probes, and secretion of prolactin into the media by using ELISA. Decidualization-inducing mixture upregulated activity of protein kinases and prolactin secretion in cells derived from all women. Of the tested chemicals, dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB) and perfluorooctanesulfonic acid (PFOS) significantly reduced decidualization as judged by the kinase markers and prolactin secretion. In addition, bisphenol A (BPA) reduced prolactin secretion but did not significantly affect activity of the kinases. None of the EDCs was cytotoxic, based on the assessment of total protein content or activity of the viability marker casein kinase 2 in lysates. These results indicate that EDCs commonly present in the blood circulation of reproductive-aged women can reduce decidualization of human endometrial stromal cells in vitro. Future studies should focus on detailed hazard assessment to define possible risks of EDC exposure to endometrial dysfunction and implantation failur