The initiation of human pregnancy is marked by the implantation of an embryo into the uterine environment; however, the underlying mechanisms remain largely elusive. To address this knowledge gap, we developed hormone-responsive endometrial organoids (EMO), termed apical-out (AO)–EMO, which emulate the in vivo architecture of endometrial tissue. The AO-EMO comprise an exposed apical epithelium surface, dense stromal cells, and a self-formed endothelial network. When cocultured with human embryonic stem cell–derived blastoids, the three-dimensional feto-maternal assembloid system recapitulates critical implantation stages, including apposition, adhesion, and invasion. Endometrial epithelial cells were subsequently disrupted by syncytial cells, which invade and fuse with endometrial stromal cells. We validated this fusion of syncytiotrophoblasts and stromal cells using human blastocysts. Our model provides a foundation for investigating embryo implantation and feto-maternal interactions, offering valuable insights for advancing reproductive medicine.

The first cell fate commitment during mammalian development is the specification of the inner cell mass and trophectoderm. This irreversible cell fate commitment should be epigenetically regulated, but the precise mechanism is largely unknown in humans. Here, we show that naïve human embryonic stem (hES) cells can transdifferentiate into trophoblast stem (hTS) cells, but primed hES cells cannot. Our transcriptome and methylome analyses reveal that a primate-specific miRNA cluster on chromosome 19 (C19MC) is active in naïve hES cells but epigenetically silenced in primed ones. Moreover, genome and epigenome editing using CRISPR/Cas systems demonstrate that C19MC is essential for hTS cell maintenance and C19MC-reactivated primed hES cells can give rise to hTS cells. Thus, we reveal that C19MC activation confers differentiation potential into trophoblast lineages on hES cells. Our findings are fundamental to understanding the epigenetic regulation of human early development and pluripotency.

Parental exposure to stress or glucocorticoids either before or during pregnancy can have profound influences on neurodevelopment, neuroendocrine function and behaviours in offspring. Specific outcomes are dependent on the nature, intensity and timing of the exposure, as well as species, sex and age of the subject. Most recently, it has become evident that outcomes are not confined to first‐generation offspring and that there may be intergenerational and transgenerational transmission of effects. There has been intense focus on the mechanisms by which such early exposure leads to long‐term and potential transgenerational outcomes, and there is strong emerging evidence that epigenetic processes (histone modifications, DNA methylation, and small non‐coding RNAs) are involved. New knowledge in this area may allow the development of interventions that can prevent, ameliorate or reverse the long‐term negative outcomes associated with exposure to early adversity. This review will focus on the latest research, bridging human and pre‐clinical studies, and will highlight some of the limitations, challenges and gaps that exist in the field.

This study aimed to investigate the association between maternal birth weight (MBW) and hypertensive disorders of pregnancy (HDP) according to the gestational age when HDP develops. A total of 77,345 subjects were included in this prospective birth cohort study. The association between MBW and HDP was investigated by a multinomial logistic regression model. Early-onset HDP (EO-HDP), preterm late-onset HDP (preterm LO-HDP), and term late-onset HDP (term LO-HDP). Lower MBW was associated with higher odds of preterm and term LO-HDP (p-values for trend < 0.0001 and = 0.0005, respectively). A linear association between MBW and EO-HDP was observed (p-values for trend = 0.0496). The shape of the association between MBW and preterm LO-HDP was a combination of the associations between MBW with EO-HDP or LO-HDP. The effect size of the association between MBW < 2,500 g and EO-HDP was lower than that of MBW < 2,500 g with preterm or term LO-HDP. The adjusted odds ratios for EO-HDP, preterm LO-HDP, and term LO-HDP in subjects with MBW < 2,500 g were 1.052 (95 % confidence interval [CI]: 0.665-1.664), 1.745 (95 % CI: 1.220-2.496), and 1.496 (95 % CI: 1.154-1.939), respectively. MBW was associated with HDP, regardless of gestational age when HDP developed. Furthermore, the association of MBW < 2,500 g with preterm or term LO-HDP was stronger than that with EO-HDP.

Objectives This study aimed to investigate the association and population-attributable fraction (PAF) of maternal smoking and secondhand smoke (SHS) exposure during pregnancy with placental abruption. Design Prospective cohort study. Setting 15 regional centres in Japan. Participants Pregnant women registered between January 2011 and March 2014 from the Japan Environment and Children’s Study. Outcome measures Data were transcribed from medical records and two self-administered questionnaires. The outcome measure was the incidence of placental abruption. Maternal smoking exposure during pregnancy was categorised based on the number of cigarettes smoked (≤10 or ≥11 cigarettes per day). SHS exposure during pregnancy was evaluated by frequency and duration (almost never or never, 1–3 days/week and/or <1 hour/day and 4–7 days/week and ≥1 hour/day). A modified Poisson regression model, adjusted for known placental abruption risk factors, calculated the risk ratio (RR) and PAF for placental abruption with a 95% Cl. Results Of the 81 974 eligible pregnant women, pregnant women smoking ≥11 cigarettes/day during pregnancy had a significantly higher risk of placental abruption. The adjusted RR (aRR) was 2.21 (95% CI 1.21 to 4.06), and the adjusted PAF (aPAF) was 1.90% (95% CI 0.09 to 3.71%). Pregnant women among never-smokers with SHS exposure of 4–7 days/week and ≥1 hour/day had a significantly higher risk (aRR: 2.34, 95% CI 1.29 to 4.28), and the aPAF was 1.89% (95% CI −0.05 to 3.83). Additionally, pregnant women among those who smoked during pregnancy with similar SHS exposure had a significantly higher risk (aRR: 2.21, 95% CI 1.30 to 3.76), with the aPAF of 2.29% (95% CI 0.11 to 4.48). Conclusions Maternal smoking and SHS exposure during pregnancy significantly contribute to the risk of placental abruption in Japan. Therefore, preventive interventions and measures to reduce exposure are required to prevent placental abruption.