Physically active pregnancies: Insights from the placenta.

Physical activity (PA) positively influences pregnancy, a critical period for health promotion, and affects placental structure and function in ways previously overlooked. Here, we summarize the current body of literature examining the association between PA, placenta biology, and physiology while also highlighting areas where gaps in knowledge exist. PA during pregnancy induces metabolic changes, influencing nutrient availability and transporter expression in the placenta. Hormones and cytokines secreted during PA contribute to health benefits, with intricate interactions in pro- and anti-inflammatory markers. Extracellular vesicles and placental "-omics" data suggest that gestational PA can shape placental biology, affecting gene expression, DNA methylation, metabolite profiles, and protein regulation. However, whether cytokines that respond to PA alter placental proteomic profiles during pregnancy remains to be elucidated. The limited research on placenta mitochondria of physically active gestational parents (gesP), has shown improvements in mitochondrial DNA and antioxidant capacity, but the relationship between PA, placental mitochondrial dynamics, and lipid metabolism remains unexplored. Additionally, PA influences the placenta-immune microenvironment, angiogenesis, and may confer positive effects on neurodevelopment and mental health through placental changes, vascularization, and modulation of brain-derived neurotrophic factor. Ongoing exploration is crucial for unraveling the multifaceted impact of PA on the intricate placental environment.

Examining the Effects of Gestational Physical Activity and Hofbauer Cell Polarization on Angiogenic Factors.

While gestational physical activity (PA) has demonstrated health benefits for both birthing parent and fetus, the mechanisms still need to be fully understood. Placental macrophages, or Hofbauer cells (HBCs), comprise a heterogenous population containing inflammatory (CD206-) and anti-inflammatory (CD206+) phenotypes. Similar to other tissue-resident macrophages (TRMs), HBCs are potential mediators of angiogenesis due to their secretion of both pro- and anti-angiogenic factors, including FGF2, VEGF, and SPRY2. While PA is associated with an increase in the proportion of VEGF- and FGF2-producing CD206+ macrophages in other tissues, the phenotypes producing FGF2, VEGF, and SPRY2 in the placenta and the associated relationships with gestational PA have not been studied. Using accelerometry, pregnant participants were classified as physically active or inactive in mid- and late-gestation. Term placenta tissue was collected at delivery and used for Western blotting and immunofluorescence to examine the protein expression of FGF2 and SPRY2, and to localize FGF2 in histological samples, respectively. Primary cultures of HBCs were used to examine the phenotypic differences in FGF2, SPRY2, and VEGF production. While no differences in the placental expression of SPRY2, total FGF2, or high-molecular-weight FGF2 were observed based on PA status, active individuals had significantly reduced levels of low-molecular-weight FGF2. Additionally, HBCs of all polarizations produce VEGF, FGF2, and SPRY2, and can form intercellular junctions and multinucleated giant cells. These findings suggest a possible relationship between PA and HBC-driven angiogenesis, providing an avenue for future exploration.

Characterization of Hofbauer cell polarization and VEGF localization in human term placenta from active and inactive pregnant individuals.

Physical activity (PA) during pregnancy is associated with parental and fetal health benefits; however, the mechanisms through which these benefits arise are yet to be fully understood. In healthy pregnancies Hofbauer cells (HBCs) comprise a heterogenous population containing CD206+ and CD206- phenotypes. In healthy pregnancies, CD206+ represent the majority, while dysregulations have been associated with pathological conditions. HBCs have also been identified as potential drivers of angiogenesis. As PA induces changes in macrophage polarization in non-pregnant populations, this novel study examined the relationship between PA and HBC polarization and to identify which HBC phenotypes express VEGF. Participants were classified as active or inactive, and immunofluorescence cell-labelling was used to quantify total HBCs, CD206+ HBCs, and the proportion of total HBCs expressing CD206. Immunofluorescent colocalization assessed which phenotypes expressed VEGF. Protein and mRNA expression of CD68 and CD206 were measured in term placenta tissue using Western blot and RT-qPCR, respectively. Both CD206+ and CD206- HBCs expressed VEGF. The proportion of CD206+ HBCs was elevated in active individuals; however, CD206 protein expression was observed to be lower in active participants. Combined with a lack of significant differences in CD206 mRNA levels, these findings suggest potential PA-mediated responses in HBC polarization and CD206 translational regulation.

Physical Activity and Weight Gain Throughout Pregnancy Are Associated With Umbilical Cord Markers.

OBJECTIVE: Maternal serum and umbilical cord (UC) lipid and glucose levels are influenced by a variety of maternal factors over the course of pregnancy, including maternal physical activity (PA) levels and gestational weight gain (GWG). However, previous research has not assessed the interaction of these 2 variables. This study investigated mid-gestation (24-28 weeks) and late gestation (34-38 weeks) maternal and UC serum lipid and glucose profiles in relation to maternal PA status and GWG, independently and in combination. METHODS: This study had a longitudinal design. Pregnant participants (n = 40) were categorized as active or inactive based on the 2019 Canadian Guideline for Physical Activity throughout Pregnancy, and GWG was categorized as insufficient, appropriate, or excessive based on 2009 Institute of Medicine recommendations. Fasting maternal serum was taken in mid- and late gestation, and venous UC serum was taken at birth. RESULTS: No relationship was found between maternal serum values and PA and/or GWG. Infants born to individuals who were physically active across pregnancy, or who were active in mid-pregnancy and had their activity status drop in late gestation, had lower UC total cholesterol levels than those who were inactive throughout pregnancy (P < 0.0001). Participants who had gained weight appropriately at mid-gestation had significantly lower UC glucose levels than those who gained weight insufficiently (P = 0.040) or excessively (P = 0.021). CONCLUSION: In our study, PA, and GWG (independently and in combination) may not have affected maternal serum; however, meeting PA recommendations at mid-gestation may provide prophylactic effects on UC serum, potentially providing long-term health benefits to the newborn.

Elucidating the interaction between maternal physical activity and circulating myokines throughout gestation: A scoping review.

Physical activity (PA) during pregnancy provides both maternal and fetal health benefits. It has been theorized that myokines, peptides secreted by contracting skeletal muscle, may play an important mechanistic role in facilitating the health benefits obtained from prenatal exercise. The objective of this review was to synthesize the current literature on the relationship between maternal PA and myokine response. A search strategy was developed using the terms pregnancy, PA, IL-6, IL-10, IL-13, and TNF-α. A systematic search was completed in July 2020, in Medline, SPORTDiscus, EMBASE, CENTRAL, and in November 2020 for unpublished dissertations (grey literature; Proquest). Both human- and animal-based studies of any design were included, while commentaries and editorial articles were excluded. Data were extracted by two independent reviewers and summarized narratively. Data were thematically summarized based on the myokine and whether findings were from human or animal studies. Ten studies were included in this review. Findings from studies that examined IL-6, IL-10, and TNF-α suggest a trimester-specific interaction between PA and myokine levels; no studies evaluated IL-13. Future research should investigate the PA-myokine relationship throughout all stages of gestation.

Physical activity differentially regulates VEGF, PlGF, and their receptors in the human placenta.

Physical activity (PA) has beneficial effects on the function of many organs by modulating their vascular development. Regular PA during pregnancy is associated with favorable short- and long-term outcomes for both mother and fetus. During pregnancy, appropriate vascularization of the placenta is crucial for adequate maternal-fetal nutrient and gas exchange. How PA modulates angiogenic factors, VEGF, and its receptors in the human placenta, is as of yet, unknown. We objectively measured the PA of women at 24-28 and 34-38 weeks of gestation. Participants were considered "active" if they had met or exceeded 150 min of moderate-intensity PA per week during their 2nd trimester. Term placenta tissues were collected from active (n = 23) or inactive (n = 22) women immediately after delivery. We examined the expression of the angiogenic factors VEGF, PlGF, VEGFR-1, and VEGFR-2 in the placenta. Western blot analysis showed VEGF and its receptor, VEGFR-1 was significantly (p < 0.05) higher both at the protein and mRNA levels in placenta from physically active compared to inactive women. No difference in VEGFR-2 was observed. Furthermore, immunohistochemistry showed differential staining patterns of VEGF and its receptors in placental endothelial, stromal, and trophoblast cells and in the syncytial brush border. In comparison, PlGF expression did not differ either at the protein or mRNA level in the placenta from physically active or inactive women. The expression and localization pattern of VEGF and its receptors suggest that PA during pregnancy may support a pro-angiogenic milieu to the placental vascular network.