Volume 04 · Issue 01 · 2022

Decidualization is the differentiation of endometrial stromal cells into secretory decidual stromal cells. Human decidualization involves some amount of signaling molecules and pathways as well as genetic reprogramming, which is driven by the postovulatory rise in progesterone levels and local cyclic adenosine monophosphate production. Decidualization extends from the primary decidual zone to the secondary decidual zone, and then exits through apoptosis. Evidences support that decidual fibroblasts function as the pool of decidual stromal cells during pregnancy. Decidualization undergoes an acute inflammatory phase, an anti-inflammatory secretory phase to the final recession phase. The decidualization of the inner layer of endometrium, termed decidua, is the most critical determinant of pregnancy success, which can promote placenta formation, modulate immune tolerance, foster resistance to oxidative stress, sense embryo quality, and control labor. Failure to adequate decidualization in terms of hormones, biochemistry, and immunology leads to adverse pregnancy outcomes, including diseases such as preeclampsia, miscarriage, premature labor, repeated implantation failures, and some age-related decline in reproductive capacity. The development of animal models and in vitro culture systems combined with emerging technologies provides a powerful system to explore the mechanism of decidualization. However, decidualization is a dynamic, multi-step process, and translating of current research progress into disease predictions and interventions for pregnancy complications remains to be achieved. The study of periodic regeneration and spontaneous decidualization of the endometrium will be beneficial to the diagnosis and treatment of pregnancy diseases.

Serving as the interface between the fetal and maternal environments during gestation, the placenta plays critical roles in the protection of the developing fetus and the maintenance of maternal health. The placenta is primarily derived from the embryonic trophectoderm which differentiates into various subtypes of trophoblast cells through villous and extravillous pathways. The interactions among trophoblasts and multiple decidual cells and immune cells at the maternal-fetal interface fundamentally form the functional units of the placenta, which are responsible for blood perfusion and maternal-fetal material exchange, immune tolerance, and the regulation of pregnancy adaptation. Defects in placental development and functional maintenance are in tight association with adverse pregnancy outcomes such as preeclampsia. In this article, we review recent advances on human trophoblast cell differentiation and the construction of placental functional units and discuss the placental and maternal factors that may contribute to the occurrence of preeclampsia.

Normal pregnancy is associated with dramatically increased estrogen biosynthesis whose role is believed to raise uterine blood flow to facilitate the bi-directional maternal-fetal exchanges of gases (O₂ and CO₂), to deliver nutrients, and exhaust wastes to support fetal development and survival. Constrained uterine blood flow in pregnancy is a leading cause of preeclampsia with fetal growth restriction, rendering investigations of uterine hemodynamics to hold a high promise to inform pathways as targets for therapeutic interventions for preeclampsia. The mechanisms of estrogen-induced uterine vasodilation in pregnancy have long been attributed to enhanced endothelium production of nitric oxide, but clinical trials targeting this pathway that dominates uterine hemodynamics have achieved no to little success. Emerging evidence has recently shown a novel proangiogenic vasodilatory role of hydrogen sulfide in regulating uterine hemodynamics in pregnancy and preeclampsia, provoking a new field of perinatal research in searching for alternative pathways for pregnancy disorders especially preeclampsia and intrauterine growth restriction. This minireview is intended to summarize the nitric oxide pathway and to discuss the emerging hydrogen sulfide pathway in modulating estrogen-induced uterine vasodilation in pregnancy and preeclampsia.

Preterm labor (before 37 weeks’ gestation) is the leading cause of neonatal mortality and morbidity, which can be divided into iatrogenic preterm labor, infectious preterm labor, and spontaneous preterm labor (sPTL). Up to now, there continue to be great difficulties in prediction and prevention of sPTL, owing to multiple risk factors, pathogenesis, and pathologic processes contributing to the event, which have not been fully clarified. Pregnancy maintenance and parturition is a complicated process with continuous maternal-fetal dialogue, in which both maternal and fetal factors participate and affect the outcome of pregnancy, including sPTL. Besides, external factors can also participate in sPTL, individually or through the interaction with internal factors. In this article, we summarize recent studies regarding sPTL from our and other groups, and discuss the risk factors and pathogenesis of preterm birth from both external and internal (maternal and fetal) aspects, so as to provide theoretical evidences for the diagnosis, prevention, and treatment of sPTL in the future.

Viral infections during pregnancy are associated with adverse pregnancy outcomes, including maternal and fetal mortality, pregnancy loss, premature labor, and congenital anomalies. Mammalian gestation encounters an immunological paradox wherein the placenta balances the tolerance of an allogeneic fetus with protection against pathogens. Viruses cannot easily transmit from mother to fetus due to physical and immunological barriers at the maternal-fetal interface posing a restricted threat to the fetus and newborns. Despite this, the unknown strategies utilized by certain viruses could weaken the placental barrier to trigger severe maternal and fetal health issues especially through vertical transmission, which was not fully understood until now. In this review, we summarize diverse aspects of the major viral infections relevant to pregnancy, including the characteristics of pathogenesis, related maternal-fetal complications, and the underlying molecular and cellular mechanisms of vertical transmission. We highlight the fundamental signatures of complex placental defense mechanisms, which will prepare us to fight the next emerging and re-emerging infectious disease in the pregnancy population.