Regulation of inflammation during gestation and birth outcomes: Inflammatory cytokine balance predicts birth weight and length

Ragsdale, Haley B.; Kuzawa, Christopher W.; Borja, Judith B.; Avila, Josephine L.; McDade, Thomas W.

doi:10.1002/ajhb.23245

Cited by 35 publications

(24 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is important to point out that there is not an international standardization in the techniques to report harmonized results either. However, some other groups reported similar cytokine concentrations to our study values (19,(39)(40)(41)(42)(43)(44)(45)(46).…”

Section: Inflammatory Profile and Osasupporting

confidence: 89%

Influence of Obstructive Sleep Apnea on Systemic Inflammation in Pregnancy

et al. 2021

View full text Add to dashboard Cite

Background: Obstructive sleep apnea (OSA) is prevalent in pregnancy and it is associated with adverse pregnancy-related outcomes such as gestational diabetes, pre-eclampsia, and low birth weight. Maternal systemic inflammation is proposed to be one of the main intermediate mechanisms. However, the effects of OSA on systemic inflammation are unknown in normal pregnancy.Methods: Women in the 3rd trimester underwent hospital polysomnography to evaluate whether OSA increases systemic inflammation in normal pregnancy and its potential association with adverse fetal outcomes. OSA was defined as an apnea–hypopnea index (AHI) of ≥ 5 h−1. Plasma cytokines levels (TNF-α, IL-1β, IL-6, IL-8, and IL-10) were determined by multiple immunoassays.Results: We included 11 patients with OSA and 22 women with AHI < 5 h−1, who were homogeneous in age, and body mass index (BMI). Women with OSA had significant higher levels of TNF-α, IL-1β, IL-8, and IL-10. We found significant correlations between AHI during REM and TNF-α (r = 0.40), IL-1β (r = 0.36), IL-6 (r = 0.52), IL-8 (r = 0.43), between obstructive apnea index and TNF-α (r = 0.46) and between AHI and IL-1β (r = 0.43). We also found that CT90% was related to IL-8 (r = 0.37). There were no significant differences in neonatal characteristics; however, we found inverse correlations between TNF-α and IL-8 with birth weight (both r = −0.48), while IL-8 showed a significant inverse relationship with neonatal gestational age (r = −0.48).Conclusions: OSA in our normal pregnancy population was associated with higher systemic inflammation, which was related to obstructive events, especially during REM sleep. Moreover, systemic inflammation was inversely correlated with neonatal birth weight and age.

show abstract

Section: Inflammatory Profile and Osasupporting

confidence: 89%

Influence of Obstructive Sleep Apnea on Systemic Inflammation in Pregnancy

et al. 2021

View full text Add to dashboard Cite

show abstract

“…A dysregulation of maternal immunity can lead to a placental invasion and a restriction of fetal growth leading to PTB, preeclampsia, and LBW. Although acute gestational stimuli such as infections are risk factors for PTB and LBW ( Park et al, 2018 ), recent studies have shown that endogenous immune processes such as the presence of chronic inflammation can influence APO in the absence of infection ( Ragsdale et al, 2019 ). At the end of the third trimester, a Th-1 pattern predominates, and some authors have considered that this change to an inflammatory environment is necessary to start delivery ( Saito et al, 2010 ), as is corroborated by the results of this research.…”

Section: Discussionmentioning

confidence: 99%

Porphyromonas gingivalis Placental Atopobiosis and Inflammatory Responses in Women With Adverse Pregnancy Outcomes

et al. 2020

View full text Add to dashboard Cite

The microbiome modulates inflammation at the fetal maternal interface on both term and preterm labor. Inflammophilic oral bacteria, such as Porphyromonas gingivalis, as well as urogenital microorganisms (UGM) could translocate to the placenta and activate immune mechanisms in decidual tissue that is associated with adverse pregnancy outcomes (APO). This study establishes the associations between the presence of microbes in the placenta and placental cytokine patterns in women who presented APO, e.g., low birth weight (LBW), preterm premature rupture of membranes (PPROM), preterm birth (PTB) and other clinical signs related to Chorioamnionitis (CA). A total of 40 pregnant women were included in the study and divided into five groups according to placental infection (PI) and APO, as follows: (1) women without PI and without APO (n = 17), (2) women with P. gingivalis-related PI and APO (n = 5), (3) women with P. gingivalis-related PI and without APO (n = 4), (4) women with PI related to UGM and APO (n = 5) and (5) women without PI with APO (n = 9). Obstetric, clinical periodontal status evaluation, and subgingival plaque sampling were performed at the time of delivery. Placental levels of interleukin IL-1β, IL-6, IL-10, IL-15, IL-17A, IL-17F, IL-21, IL-12p70, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 α (MCP-1α), granzyme B, and interferon-γ (IFN-γ) were determined using a multiplex flow cytometry assay. All patients showed a predominant Th-1 cytokine profile related to labor, characterized by IFN-γ overexpression. The analysis by groups suggests that Th-1 profile was trending to maintain cytotoxic cell activity by the expression of IL-15 and granzyme B, except for the group with P. gingivalis-related PI and APO, which exhibited a reduction of IL-10 and IL-17F cytokines (p < 0.05) and a Th-1 profile favoring macrophage activation by MCP-1 production (p < 0.05). This study confirms a pro-inflammatory pattern associated with labor, characterized by a Th-1 profile and the activity of cytotoxic cells, which is enhanced by PI with UGM. However, PI associated with P. gingivalis suggests a switch where the Th-1 profile favors an inflammatory response mediated by MCP-1 and macrophage activity as a mechanistic explanation of its possible relationship with adverse outcomes in pregnancy.

show abstract

“…A previous study found that delayed puberty following DSS treatment in mice was associated explicitly with inflammation and increased cytokine levels, and was not due merely to weight loss, and that it occurred irrespective of serum leptin and corticosterone levels [30]. Studies in human populations have also reported a correlation between inflammatory markers, progesterone levels and ovarian suppression [63], while maternal inflammation and ratios between specific cytokines was found to be associated with fetal growth rates [83]. The energetic costs of immune challenges arising from childhood in Bangladesh or prepubertal colitis in mice likely force trade-offs with other physiological systems [84,85].…”

Section: Discussionmentioning

confidence: 95%

Epigenetic regulation of 5α reductase-1 underlies adaptive plasticity of reproductive function and pubertal timing

et al. 2022

View full text Add to dashboard Cite

Background Women facing increased energetic demands in childhood commonly have altered adult ovarian activity and shorter reproductive lifespan, possibly comprising a strategy to optimize reproductive success. Here, we sought to understand the mechanisms of early-life programming of reproductive function, by integrating analysis of reproductive tissues in an appropriate mouse model with methylation analysis of proxy tissue DNA in a well-characterized population of Bangladeshi migrants in the UK. Bangladeshi women whose childhood was in Bangladesh were found to have later pubertal onset and lower age-matched ovarian reserve than Bangladeshi women who grew-up in England. Subsequently, we aimed to explore the potential relevance to the altered reproductive phenotype of one of the genes that emerged from the screens. Results Of the genes associated with differential methylation in the Bangladeshi women whose childhood was in Bangladesh as compared to Bangladeshi women who grew up in the UK, 13 correlated with altered expression of the orthologous gene in the mouse model ovaries. These mice had delayed pubertal onset and a smaller ovarian reserve compared to controls. The most relevant of these genes for reproductive function appeared to be SRD5A1, which encodes the steroidogenic enzyme 5α reductase-1. SRD5A1 was more methylated at the same transcriptional enhancer in mice ovaries as in the women’s buccal DNA, and its expression was lower in the hypothalamus of the mice as well, suggesting a possible role in the central control of reproduction. The expression of Kiss1 and Gnrh was also lower in these mice compared to controls, and inhibition of 5α reductase-1 reduced Kiss1 and Gnrh mRNA levels and blocked GnRH release in GnRH neuronal cell cultures. Crucially, we show that inhibition of this enzyme in female mice in vivo delayed pubertal onset. Conclusions SRD5A1/5α reductase-1 responds epigenetically to the environment and its downregulation appears to alter the reproductive phenotype. These findings help to explain diversity in reproductive characteristics and how they are shaped by early-life environment and reveal novel pathways that might be targeted to mitigate health issues caused by life-history trade-offs.

show abstract

Regulation of inflammation during gestation and birth outcomes: Inflammatory cytokine balance predicts birth weight and length

Cited by 35 publications

References 42 publications

Influence of Obstructive Sleep Apnea on Systemic Inflammation in Pregnancy

Influence of Obstructive Sleep Apnea on Systemic Inflammation in Pregnancy

Porphyromonas gingivalis Placental Atopobiosis and Inflammatory Responses in Women With Adverse Pregnancy Outcomes

Epigenetic regulation of 5α reductase-1 underlies adaptive plasticity of reproductive function and pubertal timing

Contact Info

Product

Resources

About