The enrichment of maternal environment prevents pre-term birth in a mice model

Abstract

Maternal lifestyle affects both mother health and pregnancy outcome in humans. Several studies have demonstrated that interventions oriented toward reducing stress and anxiety have positive effects on pregnancy complications such as preeclampsia, excessive gestational weight, gestational diabetes and preterm birth. In this work, we showed that the environmental enrichment (EE), defined as a noninvasive and biologically significant stimulus of the sensory pathway combined with voluntary physical activity, prevented preterm birth (PTB) rate by 40% in an inflammatory mouse model induced by the systemic administration of bacterial lipopolysaccharide (LPS). Furthermore, we found that EE modulates maternal metabolism and produces an anti-inflammatory environment that contributes to pregnancy maintenance. In pregnant mice uterus, EE reduces the expression of TLR4 and CD14 (the LPS receptor and its coactivator protein), preventing the LPS-induced increase in PGE2 and PGF2α release and nitric oxide synthase (NOS) activity. In cervical tissue, EE inhibits cervical ripening events, such as PGE2 release, matrix metalloproteinase (MMP)-9 increased activity and neutrophil recruitment, therefore conserving cervical function. It seems that EE exposure could mimic the stress and anxiety-reducing techniques mentioned above, explaining, at least partially, the beneficial effects of having a healthy lifestyle before and during gestation. Furthermore, we propose that designing an EE protocol for humans could be a noninvasive and preventive therapy for pregnancy complications, averting pre-term birth occurrence and dreaded sequelae that are present in the offspring born too soon.

PGE2 displays immunosuppressive effects during human active tuberculosis

“…Furthermore, we next studied the effect of PGE2 on the intracellular levels of ROS in neutrophils from HD and TB patients. As previously reported, Mtb -Ag stimulation triggered ROS production 16 (Fig. 3 E).…”

“…As shown in Fig. 2 F, Mtb -Ag stimulation increased the surface expression of SLAMF1 on neutrophils from HD and TB patients as we previously reported 16 . In contrast, antigen stimulation augmented PD-L1 levels only on neutrophils from HD (Fig.…”

“…Plasma samples were then stored at − 70 °C. PGE2 measurement was performed by radioimmunoassay (RIA) as previously described 16 . Briefly, 50 µL of plasma were diluted with 50 µL of PGs RIA buffer (7.3 mM K 2 HPO 4 •3H 2 O, 2.7 mM KH 2 PO 4 , 145 mM NaCl, 7.1 mM BSA, 15.4 mM NaN 3 , pH = 7.4) and incubated with labeled (5,6,8,9,11,12,14,15(n)– 3 H]–prostaglandin E2 (130 Ci/mmol, 100 μCi/mL, PerkinElmer, Buenos Aires, Argentina) for 1 h. Finally, a suspension of activated carbon (1%)-dextran (0.1%) was added to separate bound from free PGs.…”

Interventions for Infection and Inflammation-Induced Preterm Birth: a Preclinical Systematic Review

“…All studies used a mouse model [ 40 – 62 ]. Eighteen models (75%) induced PTB using LPS [ 40 , 42 – 45 , 47 – 51 , 53 – 56 , 58 , 59 , 61 , 62 ], and four (17%) used E. coli [ 41 , 46 , 47 , 60 ]. One study induced PTB with a monoclonal anti-CD3ε antibody [ 52 ] and another applied carbamyl-platelet activating factor (cPAF) [ 57 ].…”

Environmental Enrichment Promotes Transgenerational Programming of Uterine Inflammatory and Stress Markers Comparable to Gestational Chronic Variable Stress

“…Preconceptional and gestational EE housing contributed to pregnancy maintenance and reduced preterm birth rates by 40% in an inflammatory mouse model by dampening the inflammatory response and pro-labour mediators [ 42 ]. The EE intervention also improved behavioural, morphological, and molecular parameters resulting from the adverse programming of ancestral stress [ 43 , 44 ].…”