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Study Question: How is histiotrophic nutrition of the embryo secured during the first trimester of pregnancy?Summary Answer: Rather than specifically focusing on invasion into spiral arteries, extravillous trophoblasts also invade into uterine glands (endoglandular trophoblast) from the very beginning and open them toward the intervillous space.What Is Known Already: Extravillous trophoblasts can be found in close contact and within the lumen of uterine glands, sometimes replacing glandular epithelial cells.Study Design, Size, Duration: As well as extensive screening of specimens from first trimester placentation sites in situ we used a previously established three-dimensional co-culture in vitro model system of first trimester villous explants with non-invaded decidua parietalis.Participants/materials, Setting, Methods: First trimester placentas were obtained from elective terminations of pregnancies (n = 48) at 5-11 weeks of gestational age. A subset was processed for confrontation co-culture (n = 31). Invaded decidua basalis was obtained from 20 placentas. All tissues were sectioned, subsequently immunostained and immunodoublestained with antibodies against keratin 7 (KRT7), major histocompatibility complex, class I, G (HLA-G), matrix metallopeptidase 9 (MMP9), von Willebrand factor (VWF) and the appropriate Immunoglobulin G (IgG) negative controls. Replacement of endothelial/epithelial cells by extravillous trophoblasts was quantified semi-quantitatively. Additionally, hematoxylin and eosin-stained archival specimens from early implantation sites were assessed.Main Results and the Role Of Chance: The earliest available specimen was from around Day 10 after conception; already at this stage trophoblasts had penetrated into uterine glands and had started to replace the epithelium of the glands. Endoglandular trophoblasts replaced uterine glands in vitro and in situ and could be found in the lumen of invaded glands. Quantitative analysis revealed significantly more replacement of epithelial cells in glands (63.8 ± 22.1%) compared with endothelial cells in vessels (26.4 ± 8.8%). Accumulated detached glandular epithelial cells could be repeatedly observed in the lumen of invaded glands. Additionally, in areas of trophoblast invasion the glandular epithelium seemed to be completely disintegrated compared with glandular epithelium in the non-invaded parts of the decidua. Whole tissue specimens were used in vitro and in situ instead of cell lines; these systems mostly maintain the context of the in vivo situation.Limitations, Reasons For Caution: This is a descriptive study supported by in vitro experiments. However, a histological section will always only be a snapshot and quantification from histological sections has its limitations.Wider Implications Of the Findings: This study further strengthens the hypothesis of histiotrophic nutrition of the embryo prior to the establishment of the maternal blood flow toward the placenta. Invasion of uterine glands by endoglandular trophoblasts may have more impact on the outcome of early pregnancy than assumed up to now. [ABSTRACT FROM AUTHOR]

BACKGROUND: Routes of trophoblast invasion seem to be clear, whereas specific invasive pathways need further elucidation. Extravillous trophoblasts (EVTs) transform spiral arteries to guarantee appropriate blood flow to the placenta in the second trimester. Embryo nutrition during the first trimester is thought to be histiotrophic, whereas proof that EVTs also invade uterine glands is lacking. We developed novel three-dimensional confrontation co-culture models to elucidate invasion of EVTs into uterine glands. [ABSTRACT FROM PUBLISHER]

STUDY QUESTION Do decidual natural killer (dNK) cells and decidual macrophages (dMph) become enriched in the vicinity of the trophoblast invasion front? SUMMARY ANSWER Morphometric image analysis and areal cell density calculations, which excluded observer bias, showed an enrichment of decidual leukocytes in the neighbourhood of the trophoblast invasion front. WHAT IS KNOWN ALREADY In previous studies, the number of decidual leukocytes was visually counted in medium- or high power fields. These methods, however, cannot reveal the exact spatial relationship between leukocytes and invasive trophoblast cells, and are therefore prone to subjective errors. Thus, a more objective approach is required. STUDY DESIGN, SIZE, DURATION Applying a new method of morphometric image analysis, leukocyte populations were studied in human tissue fragments derived from first trimester placentation sites (n = 7) as well as in co-cultures of first trimester decidual tissue with placental villi of the same pregnancy representing an appropriate in vitro model of trophoblast invasion (n = 15). PARTICIPANTS/MATERIALS, SETTINGS, METHODS First trimester decidual tissue was obtained from women undergoing elective terminations of pregnancy at 7–10 weeks of gestational age. Tissue sections were double-stained immunohistochemically for markers of dNK cells or dMph on one hand, and for invasive extravillous trophoblast cells on the other. To analyse the distribution of leukocytes, distinct cell compartments as well as cell neighbourhood areas were defined. Finally, relative areal cell densities were calculated and these data were compared with those of an in vitro model of trophoblast invasion as well as with tissue fragments derived from decidua parietalis without trophoblast cells. MAIN RESULTS AND THE ROLE OF CHANCE At first trimester placentation sites, a higher density of dNK cells as well as of dMph was found in close proximity to the invasive trophoblast (P ≤ 0.01), compared with the average areal cell density of decidual leukocytes in the tissue with exclusion of the trophoblast. The highest areal cell density of leukocytes was determined up to a distance of 20 μm from the trophoblast cells, whereas in more distant regions it was even lower than average, indicating a migration of these leukocytes towards the trophoblast invasion front. In the three-dimensional co-culture model, however, we found an enrichment of dMph (P ≤ 0.01) but not of dNK cells (P > 0,05) in the neighbourhood of the invasive trophoblast. LIMITATIONS, REASONS FOR CAUTION The morphometric image analysis depends on intense immunohistochemical staining that is free of background and cross-reactivity. WIDER IMPLICATIONS OF THE FINDINGS The presented method will be useful not only for the investigation of recurrent miscarriage but also in the fields of tumour immunology and inflammation. STUDY FUNDING/COMPETING INTEREST(S) The study was supported by the European Commission (Network of Excellence ‘The Control of Embryo Implantation (EMBIC)’, FP6-512040, lead researcher: P.S.), and by the Franz Lanyar Foundation of the Medical University of Graz, Austria (Grant #347). None of the authors declared a conflict of interests. [ABSTRACT FROM PUBLISHER]

BACKGROUND: Season of birth has been reported to affect later reproduction in samples of pre‐modern women and contemporary men. METHODS: To examine whether the effect of birth date is also valid in contemporary women, we investigated the association between birth month and measures of reproductive performance (number of live‐born children, % childless individuals) in a representative sample of contemporary Austrian women. RESULTS: Among reproducing women, birth month is significantly associated with the number of live‐born children (n = 2839, P = 0.032). On average, women born in summer months have fewer children than women born during the remainder of the year. No association between birth month and the percentage of childless individuals was found. CONCLUSIONS: As has been reported in pre‐modern women, month of birth also appears to affect later reproduction in contemporary women. [ABSTRACT FROM AUTHOR]