Survivors of preterm birth struggle with multitudes of disabilities due to improper in utero programming of various tissues and organ systems contributing to adult-onset diseases at a very early stage of their lives. Therefore, the persistent rates of low birth weight (birth weight < 2,500 grams), as well as rates of neonatal and maternal morbidities and mortalities, need to be addressed. Active research throughout the years has provided us with multiple theories regarding the risk factors, initiators, biomarkers, and clinical manifestations of spontaneous preterm birth. Fetal organs, like the placenta and fetal membranes, and maternal tissues and organs, like the decidua, myometrium, and cervix, have all been shown to uniquely respond to specific exogenous or endogenous risk factors. These uniquely contribute to dynamic changes at the molecular and cellular levels to effect preterm labor pathways leading to delivery. Multiple intervention targets in these different tissues and organs have been successfully tested in preclinical trials to reduce the individual impacts on promoting preterm birth. However, these preclinical trial data have not been effectively translated into developing biomarkers of high-risk individuals for an early diagnosis of the disease. This becomes more evident when examining the current global rate of preterm birth, which remains staggeringly high despite years of research. We postulate that studying each tissue and organ in silos, as how the majority of research has been conducted in the past years, is unlikely to address the network interaction between various systems leading to a synchronized activity during either term or preterm labor and delivery. To address current limitations, this review proposes an integrated approach to studying various tissues and organs involved in the maintenance of normal pregnancy, promotion of normal parturition, and more importantly, contributions towards preterm birth. We also stress the need for biological models that allows for concomitant observation and analysis of interactions, rather than focusing on these tissues and organ in silos.

Cervical cancer is estimated to cause 341,831 deaths each year, with 9 of 10 deaths occurring in developing countries. Over the past decade, there has been a significant increase in cervical cancer incidence among women in the Philippines. Persistent infection with high-risk human papillomavirus (HPV) is the well-established necessary cause of cervical cancer. Based on limited studies conducted in the Philippines, the prevalence of infection with any HPV genotype was 93.8% for cervical squamous cell carcinoma and 90.9% for cervical adenocarcinomas. HPV types 16 and 18 were the most common HPV genotypes among Filipino patients with cervical cancer. On the other hand, the incidence of HPV infection among Filipino women with normal cervices was 9.2%. The World Health Organization has launched a global agenda of eliminating HPV infection by 2030. One of its key milestones is to vaccinate 90% of girls with the HPV vaccine by 15 years. However, the HPV vaccination rate among Filipino women remains to be unsatisfactory. HPV vaccination has only been included in the Philippine Department of Health's community-based National Immunization Program in 2015. Despite these efforts, the Philippines currently ranks last on HPV program coverage among low-middle income countries, with coverage of only 23% of the target female population for the first dose and 5% for the final dose. The principal reason for the non-acceptance of HPV vaccines was the perceived high cost of vaccination. The low utilization of available cervical cancer screening tests such as Pap smear and visual inspection with acetic acid hampered the Philippines' control and prevention of HPV infection and cervical cancer. Among those diagnosed with cervical cancer in the Philippines, only an estimated 50% to 60% receive some form of treatment. To this end, we summarize the burden of HPV infection and cervical cancer on Filipinos and the risk factors associated with the disease. We present the current screening, diagnostics, treatment, and prevention of HPV-related diseases in the Philippines. Lastly, we also propose solutions on how each building block in health systems can be improved to eliminate HPV infection and reduce the burden of cervical cancer in the Philippines.

Chorion trophoblasts (CTCs) and immune cell-enriched decidua (DECs) comprise the maternal-fetal membrane interface called the chorio-decidual interface (CDi) which constantly gets exposed to maternal stressors without leading to labor activation. This study explored how CTCs act as a barrier at CDi. The roles of human leukocyte antigen (HLA)-G and progesterone receptor membrane component 2 (PGRMC2) in mediating immune homeostasis were also investigated. The CDi was recreated in a two-chamber microfluidic device (CDi-on-chip) with an outer chamber of primary DECs and immune cell line-derived innate immune cells and an inner chamber of wild-type or PGRMC2 or HLA-G knockout immortalized CTCs. To mimic maternal insults, DECs were treated with lipopolysaccharide, poly(I:C), or oxidative stress inducer cigarette smoke extract. Expression levels of inflammation and immunity genes via targeted RNA sequencing, production of soluble mediators, and immune cell migration into CTCs were determined. In CDi-on-chip, decidua and immune cells became inflammatory in response to insults while CTCs were refractory, highlighting their barrier function. HLA-G and PGRMC2 are found to be vital to immune homeostasis at the CDi, with PGRMC2 serving as an upstream regulator of inflammation, HLA-G expression, and mesenchymal-epithelial transition, and HLA-G serving as a frontline immunomodulatory molecule, thus preventing fetal membrane compromise.

During human pregnancy the chorion (fetal) lines decidua (maternal) creating the feto–maternal interface. Despite their proximity, resident decidual immune cells remain quiescent during gestation and do not invade the chorion. Infection and infiltration of activated immune cells toward the chorion are often associated with preterm birth. However, the mechanisms that maintain choriodecidual immune homeostasis or compromise immune barrier functions remain unclear. To understand these processes, a two-chamber microphysiological system (MPS) was created to model the human choriodecidual immune interface under normal and infectious conditions in vitro. This MPS has outer (fetal chorion trophoblast cells) and inner chambers (maternal decidual + CD45+ cells [70:30 ratio]) connected by microchannels. Decidual cells were treated with LPS to mimic maternal infection, followed by immunostaining for HLA-DR and HLA-G, immune panel screening by imaging cytometry by time of flight, and immune regulatory factors IL-8 and IL-10, soluble HLA-G, and progesterone (ELISA). LPS induced a proinflammatory phenotype in the decidua characterized by a decrease in HLA-DR and an increase in IL-8 compared with controls. LPS treatment increased the influx of immune cells into the chorion, indicative of chorionitis. Cytometry by time of flight characterized immune cells in both chambers as active NK cells and neutrophils, with a decrease in the abundance of nonproinflammatory cytokine-producing NK cells and T cells. Conversely, chorion cells increased progesterone and soluble HLA-G production while maintaining HLA-G expression. These results highlight the utility of MPS to model choriodecidual immune cell infiltration and determine the complex maternal–fetal crosstalk to regulate immune balance during infection.