Molecular pathways in placental-fetal development and disruption

Adibi, Jennifer J.; Zhao, Yaqi; Koistinen, Hannu; Mitchell, Rod T.; Barrett, Emily S.; Miller, Richard; O'Connor, Thomas G.; Xun, Xiaoshuang; Liang, Hai-Wei; Birru, Rahel; Smith, Megan; Moog, Nora K.

doi:10.1016/j.mce.2023.112075

Cited by 4 publications

(5 citation statements)

References 424 publications

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“…Based on our findings, we posit that there is a need in epidemiological research to measure the alpha and beta forms of hCG in pregnancy, especially in the first trimester when serum levels of the alpha and beta subunits are not well correlated. 43 …”

Section: Discussionmentioning

confidence: 99%

“… 37 Several other critical roles, that may be independent of LHCGR, 38 , 39 have been proposed. 40 – 43 There are four forms of hCG, including the intact hormone (intact hCG, which is a heterodimer of alpha- and beta-subunits), free

subunit (

), free

subunit (

), and hyperglycosylated intact hCG (h-hCG). 37 Serum levels of hCG generally increase rapidly during the first trimester with a peak at 9 to 10 wk.…”

Section: Introductionmentioning

confidence: 99%

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Associations of Serum Perfluoroalkyl Substances and Placental Human Chorionic Gonadotropin in Early Pregnancy, Measured in the UPSIDE Study in Rochester, New York

Liang,

Koistinen,

Barrett

et al. 2024

Environ Health Perspect

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Background: Per- and polyfluoroalkyl substances (PFAS) are widely detected in pregnant women and associated with adverse outcomes related to impaired placental function. Human chorionic gonadotropin (hCG) is a dimeric glycoprotein hormone that can indicate placental toxicity. Objectives: Our aim was to quantify the association of serum PFAS with placental hCG, measured as an intact molecule (hCG), as free alpha-( ) and beta-subunits ( ), and as a hyperglycosylated form (h-hCG), and evaluate effect measure modification by social determinants and by fetal sex. Methods: Data were collected from 326 pregnant women enrolled from 2015 to 2019 in the UPSIDE study in Rochester, New York. hCG forms were normalized for gestational age at the time of blood draw in the first trimester [multiple of the median (MoM)]. Seven PFAS were measured in second-trimester maternal serum. Multivariate imputation by chained equations and inverse probability weighting were used to evaluate robustness of linear associations. PFAS mixture effects were estimated by Bayesian kernel machine regression. Results: Perfluorohexane sulfonic acid (PFHxS) [ : 0.29 log MoM units per log PFHxS; 95% confidence interval (CI): 0.08, 0.51] and perfluorodecanoic acid (PFDA) (hCG: ; 95% CI: , ) were associated with hCG in the single chemical and mixture analyses. The PFAS mixture was negatively associated with and positively with . Subgroup analyses revealed that PFAS associations with hCG differed by maternal race/ethnicity and education. Perfluoropentanoic acid (PFPeA) was associated with only in Black participants ( ; 95% CI: , ) and in participants with high school education or less ( ; 95% CI: , ); conversely, perfluorononanoic acid (PFNA) was negatively associated with only in White participants ( ; 95% CI: , ) and with only in participants with a college education or greater ( ; 95% CI: , ). These findings were robust to testing for selection bias, confounding bias, and left truncation bias where PFAS detection frequency was . Two associations were negative in male (and null in female) pregnancies: Perfluoroundecanoic acid (PFUnDA) with , and PFNA with h-hCG. Conclusions: Evidence was strongest for the association between PFHxS and PFDA with hCG in all participants and for PFPeA and PFNA within subgroups defined by social determinants and fetal sex. PFAS mixture associations with and differed, suggesting subunit-specific types of toxicity and/or regulation. Future studies will evaluate the biologic...

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Section: Discussionmentioning

confidence: 99%

subunit (

), free

subunit (

), and hyperglycosylated intact hCG (h-hCG). 37 Serum levels of hCG generally increase rapidly during the first trimester with a peak at 9 to 10 wk.…”

Section: Introductionmentioning

confidence: 99%

Associations of Serum Perfluoroalkyl Substances and Placental Human Chorionic Gonadotropin in Early Pregnancy, Measured in the UPSIDE Study in Rochester, New York

Liang,

Koistinen,

Barrett

et al. 2024

Environ Health Perspect

Self Cite

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“…Leptin is produced mainly in adipose tissue, and circulating leptin levels reflect body adiposity. However, it is also produced in other sites such as the stomach, skeletal muscles, pituitary gland, mammary gland [2], and placenta [3].…”

Section: Introductionmentioning

confidence: 99%

“…Different isoforms of the leptin receptor are generated from alternative splicing of the human ob-R messenger RNA (mRNA), which encodes the leptin receptor [8]. The ob gene, related to leptin, is expressed in the placenta, which is one of the main sources of fetal leptin during gestation [3]. Leptin is important in regulating gestational metabolism and body weight and has been associated with conditions such as obesity and malnutrition during pregnancy [3].…”

Section: Introductionmentioning

confidence: 99%

“…The ob gene, related to leptin, is expressed in the placenta, which is one of the main sources of fetal leptin during gestation [3]. Leptin is important in regulating gestational metabolism and body weight and has been associated with conditions such as obesity and malnutrition during pregnancy [3]. Studies indicate that these regulatory processes play a fundamental role in early pregnancy and later stages of embryonic and fetal development, influencing long-term effects that may persist into adulthood [9,10].…”

Section: Introductionmentioning

confidence: 99%

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The Potential Role of Leptin in the Regulation of Maternal Weight during Pregnancy and Its Impact on Neonate Weight and Apgar

Fonseca,

Souza-Carmo,

Ruas

et al. 2024

Obesities

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Leptin is secreted by adipose tissue and expressed in several organs, including the placenta. We investigated the influence of leptin in maternal blood on leptin expression and concentration in the placenta and umbilical cord and its influence on fetal weight and conditions at the time of birth. Twenty-five parturients were recruited, and after childbirth, placental tissue fragments, umbilical arteries, and vein blood were collected. According to leptin concentration in maternal peripheral blood, parturients were divided into low and high leptin groups. Mothers in the high-leptin group had higher age, pre-pregnancy weight, pre-pregnancy BMI, and weight in late pregnancy than mothers in the low-leptin group. Children of mothers in the high-leptin group presented an Apgar score modestly lower than those of the low-leptin group. No differences were observed in leptin concentrations in the umbilical artery and vein. However, the leptin retained in the fetus increased in the high-leptin group compared to the low-leptin group. We observed a negative correlation between fetal leptin retained and maternal age in the low-leptin group. In the high-leptin group, placental leptin concentration was positively correlated with maternal weight in late pregnancy. Nonetheless, the expression of the leptin receptor (Ob-Rb) was negatively correlated with newborn length. In conclusion, this study found a positive correlation between maternal leptin levels and maternal pre-pregnancy weight, BMI, and fetal birth weight. These findings suggest a potential role of leptin in maternal weight regulation during pregnancy and fetal growth.

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Mediation Analysis using Semi-parametric Shape-Restricted Regression with Applications

Yin,

Jeong,

Qin

et al. 2024

Sankhya B

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Often linear regression is used to estimate mediation effects. In many instances the underlying relationships may not be linear. Although, the exact functional form of the relationship may be unknown, based on the underlying science, one may hypothesize the shape of the relationship. For these reasons, we develop a novel shape-restricted inference-based methodology for conducting mediation analysis. This work is motivated by an application in fetal endocrinology where researchers are interested in understanding the effects of pesticide application on birth weight, with human chorionic gonadotropin (hCG) as the mediator. Using the proposed methodology on a population-level prenatal screening program data, with hCG as the mediator, we discovered that while the natural direct effects suggest a positive association between pesticide application and birth weight, the natural indirect effects were negative.

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Molecular pathways in placental-fetal development and disruption

Cited by 4 publications

References 424 publications

Associations of Serum Perfluoroalkyl Substances and Placental Human Chorionic Gonadotropin in Early Pregnancy, Measured in the UPSIDE Study in Rochester, New York

Associations of Serum Perfluoroalkyl Substances and Placental Human Chorionic Gonadotropin in Early Pregnancy, Measured in the UPSIDE Study in Rochester, New York

The Potential Role of Leptin in the Regulation of Maternal Weight during Pregnancy and Its Impact on Neonate Weight and Apgar

Mediation Analysis using Semi-parametric Shape-Restricted Regression with Applications

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