Dataset Information

Maternal steroids during pregnancy and their associations with ambient air pollution and temperature during preconception and early gestational periods

ABSTRACT: Hormones play critical roles in facilitating pregnancy progression and the onset of parturition. Several classes of environmental contaminants, including fine particulate matter (PM_2.5) and ambient temperature, have been shown to alter hormone biosynthesis or activity. However, epidemiologic research has not considered PM_2.5 in relation to a broader range of steroid hormones, particularly in pregnant women. Using metabolomics data collected within 20-40 weeks of gestation in an ethnically diverse pregnancy cohort study, we identified 42 steroid hormones that we grouped into five classes (pregnenolone, androgens, estrogens, progestin, and corticosteroids) based on their biosynthesis type. We found that exposure to PM_2.5 during the pre-conception and early prenatal periods was associated with higher maternal androgen concentrations in late pregnancy. We also detected a positive association between early pregnancy PM_2.5 exposure and maternal pregnenolone levels and a marginal positive association between early pregnancy PM_2.5 exposure and progestin levels. When considering each hormone metabolite individually, we found positive associations between early pregnancy PM_2.5 exposure and five steroids, two of which survived multiple comparison testing: 11beta-hydroxyandrosterone glucuronide (a pregnenolone steroid) and adrosteroneglucuronide (a progestin steroid). None of the steroid classes were statistically significant associated with ambient temperature. In sex-stratified analyses, we did not detect any sex differences in our associations. This is the first study showing that exposure to fine particulate matter during the pre-conception and early prenatal periods can lead to altered steroid adaptation during the state of pregnancy, which has been shown to have potential consequences on maternal and child health.

INSTRUMENT(S): Q Exactive

SUBMITTER: Rosalind Wright

PROVIDER: MTBLS2245 | MetaboLights | 2024-06-27

REPOSITORIES: MetaboLights

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Dataset's files

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			Action	DRS
	MTBLS2245	Other
	FILES	Other
	a_MTBLS2245_METHOD1_POS_1_metabolite_profiling_mass_spectrometry.txt	Txt
	a_MTBLS2245_METHOD2_POS_2_metabolite_profiling_mass_spectrometry.txt	Txt
	a_MTBLS2245_METHOD3_NEG_1_metabolite_profiling_mass_spectrometry.txt	Txt

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Publications

Maternal steroids during pregnancy and their associations with ambient air pollution and temperature during preconception and early gestational periods.

Colicino Elena E Cowell Whitney W Foppa Pedretti Nicolo N Joshi Anu A Youssef Oulhote O Just Allan C AC Kloog Itai I Petrick Lauren L Niedzwiecki Megan M Wright Robert O RO Wright Rosalind J RJ

Environment international 20220525

Hormones play critical roles in facilitating pregnancy progression and the onset of parturition. Several classes of environmental contaminants, including fine particulate matter (PM<sub>2.5</sub>) and ambient temperature, have been shown to alter hormone biosynthesis or activity. However, epidemiologic research has not considered PM<sub>2.5</sub> in relation to a broader range of steroid hormones, particularly in pregnant women. Using metabolomics data collected within 20-40 weeks of gestation i ...[more]

PMID: 35700570

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Project description:The LH-like molecule chorionic gonadotropin (CG) is secreted by the macaque conceptus during and following implantation, M-bM-^@M-^\rescuingM-bM-^@M-^] the CL from impending regression and extending its functional lifespan in early pregnancy for approximately two weeks. CG binds to the same receptor as LH; i.e., LHCGR, and promotes production of steroids and other factors such as relaxin (RLN1). Our research group recently used AffymetrixM-bM-^DM-" rhesus macaque total genome arrays to compare the effects of CG on the luteal transcriptome from rhesus females during simulated early pregnancy (SEP) with changes during luteal regression in the non-fecund menstrual cycle. This analysis demonstrated that CG-rescue affected expression levels of 4,500 mRNA transcripts between days 10 and 15 of the luteal phase. Previous analyses indicated that a portion of the transcriptome in the macaque CL of the menstrual cycle was regulated indirectly by LH via the local actions of steroid hormones, including progesterone (P). Therefore, this study was designed to distinguish CG-regulated luteal genes that are dependent versus independent of local steroid (P) action. A protocol of increasing dosages of hCG (SEP) was begun on day 9 of the luteal phase in rhesus females combined with concurrent administration of the 3BHSD inhibitor trilostane (TRL) +/- the synthetic progestin (P) R5020. CL were collected on day 10 (no treatment) of the luteal phase to serve as a baseline comparison (n=8), 1 day of SEP (Day 10+hCG+/-TRL+/-R5020) and 6 days of SEP (Day 15+hCG+/-TRL+/-R5020); n=4/group. In the presence of CG, treatment with TRL reduced serum P levels to less than 1 ng/ ml after 1 day and all of the Day 15+h+TRL-treated females initiated menses before CL collection. The isolated CL were processed for total RNA and hybridized to microarrays. Compared to hCG treatment alone, 50 significantly altered mRNA transcripts were identified on day 10, rising to 95 on day 15 (P<0.05, M-bM-^IM-% 2-fold change in gene expression). The mRNA levels for several genes were validated in CL by real-time PCR. RNL1 levels increased with CG-treatment, but were not affected by steroid ablation, similar to previously reported relaxin protein expression. Steroid-sensitive genes included CDH11, IL1RN, INSL3, LDLR, OPA1, SERPINE1, SFRP4, and TNSF13B1; however differential sensitivity was observed and effects of steroid ablation and P replacement varied by day. Expression of some genes (e.g., 3BHSD2, ADAMTS1, ADAMTS5, MMP9, STAR, and VEGFA) previously identified as steroid regulated in the macaque CL during the menstrual cycle were not significantly altered by steroid ablation and P replacement during CG exposure in SEP. These data indicate that the majority of CG-regulated luteal transcripts are differentially expressed independently of local steroid actions. The proportion of steroid sensitive mRNA transcripts in the presence of CG is much smaller than in the presence of LH during the non-fecund cycle. Nevertheless, the steroid-regulated genes in the macaque CL may be essential during early pregnancy, based on the previous report that TRL treatment initiates premature structural regression of the CL during SEP. These data reinforce the concept that the structure, function, and regulation of the rescued CL in early pregnancy is different from the CL of the menstrual cycle. A protocol of increasing dosages of hCG (SEP) was begun on day 9 of the luteal phase in rhesus females combined with concurrent administration of the 3BHSD inhibitor trilostane (TRL) +/- the synthetic progestin (P) R5020. CL were collected on day 10 (no treatment) of the luteal phase to serve as a baseline comparison (n=8), 1 day of SEP (Day 10+hCG+/-TRL+/-R5020) and 6 days of SEP (Day 15+hCG+/-TRL+/-R5020); n=4/group.The isolated CL were processed for total RNA and hybridized to Affymetrix Rhesus Genome microarrays.