The impact of endocrine-disrupting chemicals on stem cells: Mechanisms and implications for human health.

Endocrine-disrupting chemicals (EDCs) are compounds, either natural or man-made, that interfere with the normal functioning of the endocrine system. There is increasing evidence that exposure to EDCs can have profound adverse effects on reproduction, metabolic disorders, neurological alterations, and increased risk of hormone-dependent cancer. Stem cells (SCs) are integral to these pathological processes, and it is therefore crucial to understand how EDCs may influence SC functionality. This review examines the literature on different types of EDCs and their effects on various types of SCs, including embryonic, adult, and cancer SCs. Possible molecular mechanisms through which EDCs may influence the phenotype of SCs are also evaluated. Finally, the possible implications of these effects on human health are discussed. The available literature demonstrates that EDCs can influence the biology of SCs in a variety of ways, including by altering hormonal pathways, DNA damage, epigenetic changes, reactive oxygen species production and alterations in the gene expression patterns. These disruptions may lead to a variety of cell fates and diseases later in adulthood including increased risk of endocrine disorders, obesity, infertility, reproductive abnormalities, and cancer. Therefore, the review emphasizes the importance of raising broader awareness regarding the intricate impact of EDCs on human health.

Effects of endogenous testosterone on oscillatory activity during verbal working memory in youth.

Testosterone levels sharply rise during the transition from childhood to adolescence and these changes are known to be associated with changes in human brain structure. During this same developmental window, there are also robust changes in the neural oscillatory dynamics serving verbal working memory processing. Surprisingly, whereas many studies have investigated the effects of chronological age on the neural oscillations supporting verbal working memory, none have probed the impact of endogenous testosterone levels during this developmental period. Using a sample of 89 youth aged 6-14 years-old, we collected salivary testosterone samples and recorded magnetoencephalography during a modified Sternberg verbal working memory task. Significant oscillatory responses were identified and imaged using a beamforming approach and the resulting maps were subjected to whole-brain ANCOVAs examining the effects of testosterone and sex, controlling for age, during verbal working memory encoding and maintenance. Our primary results indicated robust testosterone-related effects in theta (4-7 Hz) and alpha (8-14 Hz) oscillatory activity, controlling for age. During encoding, females exhibited weaker theta oscillations than males in right cerebellar cortices and stronger alpha oscillations in left temporal cortices. During maintenance, youth with greater testosterone exhibited weaker alpha oscillations in right parahippocampal and cerebellar cortices, as well as regions across the left-lateralized language network. These results extend the existing literature on the development of verbal working memory processing by showing region and sex-specific effects of testosterone, and are the first results to link endogenous testosterone levels to the neural oscillatory activity serving verbal working memory, above and beyond the effects of chronological age.

Perspective: the evolution of hormones and person perception-a quantitative genetic framework.

Evolutionary biology provides a unifying theory for testing hypotheses about the relationship between hormones and person perception. Person perception usually receives attention from the perspective of sexual selection. However, because person perception is one trait in a suite regulated by hormones, univariate approaches are insufficient. In this Perspectives article, quantitative genetics is presented as an important but underutilized framework for testing evolutionary hypotheses within this literature. We note tacit assumptions within the current literature on psychiatric genetics, which imperil the interpretation of findings thus far. As regulators of a diverse manifold of traits, hormones mediate tradeoffs among an array of functions. Hormonal pleiotropy also provides the basis of correlational selection, a process whereby selection on one trait in a hormone-mediated suite generates selection on the others. This architecture provides the basis for conflicts between sexual and natural selection within hormone-mediated suites. Due to its role in person perception, psychiatric disorders, and reproductive physiology, the sex hormone estrogen is highlighted as an exemplar here. The implications of this framework for the evolution of person perception are discussed. Empirical quantification of selection on traits within hormone-mediated suites remains an important gap in this literature with great potential to illuminate the fundamental nature of psychiatric disorders.

Alfin-like (AL) transcription factor family in Oryza sativa L.: Genome-wide analysis and expression profiling under different stresses.

Oryza sativa L. is the world's most essential and economically important food crop. Climate change and ecological imbalances make rice plants vulnerable to abiotic and biotic stresses, threatening global food security. The Alfin-like (AL) transcription factor family plays a crucial role in plant development and stress responses. This study comprehensively analyzed this gene family and their expression profiles in rice, revealing nine AL genes, classifying them into three distinct groups based on phylogenetic analysis and identifying four segmental duplication events. RNA-seq data analysis revealed high expression levels of OsALs in different tissues, growth stages, and their responsiveness to stresses. RT-qPCR data showed significant expression of OsALs in different abiotic stresses. Identification of potential cis-regulatory elements in promoter regions has also unveiled their involvement. Tertiary structures of the proteins were predicted. These findings would lay the groundwork for future research to reveal their molecular mechanism in stress tolerance and plant development.

Health risk and germ cell toxicity of five commercially available sachet waters in Nigeria: a public health concern.

Background: Sachet water is the most common form of portable water commercially available in Nigeria. Methodology: Using the murine sperm count and sperm abnormality assay, the germ cell toxicity of five common commercially available sachet waters in Nigeria was assessed in this study. The levels of hormones such as Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH) and Total Testosterone (TT); and activities of catalase (CAT), alanine aminotransferase (ALT), superoxide dismutase (SOD), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were evaluated. The heavy metal and physicochemical parameters of the sachet waters were also analyzed. Healthy male mice were allowed to freely drink the sachet waters for 35 days after which they were sacrificed. Results: The findings indicated that the concentrations of some heavy metals (As, Cr, and Cd) in the sachet waters exceeded the limit by regulatory organizations. The data of the total carcinogenic risk (TCR) and total non-carcinogenic risk (THQ) of some heavy metals associated with the ingestion of sachet water for adults and children showed that the values exceeded the acceptable threshold, and thus, is indicative of a high non-carcinogenic and carcinogenic risks. The data of the sperm abnormality assay showed that in the exposed mice, the five sachet waters induced a statistically significant (P < 0.05) increase in abnormal sperm cells and a significantly lower mean sperm count. Additionally noted were changes in the serum activities of TT, FSH, ALP, AST, ALT, and LH. Conclusion: Thus, the sachet waters studied contained agents that can induce reproductive toxicity in exposed humans. This is of public health importance and calls for immediate action by regulatory bodies.

The impact of environmental factors and contaminants on thyroid function and disease from fetal to adult life: current evidence and future directions.

The thyroid gland regulates most of the physiological processes. Environmental factors, including climate change, pollution, nutritional changes, and exposure to chemicals, have been recognized to impact thyroid function and health. Thyroid disorders and cancer have increased in the last decade, the latter increasing by 1.1% annually, suggesting that environmental contaminants must play a role. This narrative review explores current knowledge on the relationships among environmental factors and thyroid gland anatomy and function, reporting recent data, mechanisms, and gaps through which environmental factors act. Global warming changes thyroid function, and living in both iodine-poor areas and volcanic regions can represent a threat to thyroid function and can favor cancers because of low iodine intake and exposure to heavy metals and radon. Areas with high nitrate and nitrite concentrations in water and soil also negatively affect thyroid function. Air pollution, particularly particulate matter in outdoor air, can worsen thyroid function and can be carcinogenic. Environmental exposure to endocrine-disrupting chemicals can alter thyroid function in many ways, as some chemicals can mimic and/or disrupt thyroid hormone synthesis, release, and action on target tissues, such as bisphenols, phthalates, perchlorate, and per- and poly-fluoroalkyl substances. When discussing diet and nutrition, there is recent evidence of microbiome-associated changes, and an elevated consumption of animal fat would be associated with an increased production of thyroid autoantibodies. There is some evidence of negative effects of microplastics. Finally, infectious diseases can significantly affect thyroid function; recently, lessons have been learned from the SARS-CoV-2 pandemic. Understanding how environmental factors and contaminants influence thyroid function is crucial for developing preventive strategies and policies to guarantee appropriate development and healthy metabolism in the new generations and for preventing thyroid disease and cancer in adults and the elderly. However, there are many gaps in understanding that warrant further research.

Adult Female Acne: Managing the Hormones.

Acne is a common inflammatory condition of the skin worldwide. The skin is an endocrine organ and hormones are a key pathogenic factor in all types of acne with a particularly important role in adult female acne pathogenesis and management. In females, we have the unique opportunity to manipulate hormones systemically to successfully manage acne and, more recently with the approval of clascoterone 1% cream, we can target the hormones topically in both genders. The intent of this paper is to provide physicians with an up-to-date clinically relevant review of the role of hormones in acne, the impact of currently available contraceptives and therapies available to target hormones in acne.

The implications of hormone treatment for cancer risk, screening and treatment in transgender individuals.

There is evidence that gender-affirming hormone treatment (GAHT) for transgender individuals modulates their risk for specific malignancies including breast and prostate cancer, and meningiomas. However, there is insufficient data to make precise risk estimates accounting for age and inherited cancer risk. As such, screening recommendations remain broad. Even less evidence exists for best practice in the management of active or historical cancers in the transgender population. Guidance is therefore mainly extrapolated from cisgender populations but with considerations of the significant benefits of GAHT in the face of any hormonal risk. Clinical experience, the multidisciplinary team and shared decision making with the patient are vital in providing person-centred care, while further research is acquired.

Hormonal contraceptives and behavior: Updating the potent state of the nascent science.

Hundreds of millions of people worldwide use hormonal contraceptives (HCs), which have been an essential part of women's reproductive health care for decades. Throughout that time, however, research on the neural and behavioral consequences of HCs was minimal and plagued by poor methodology. HC effects - and users - were assumed to be homogenous. Fortunately, there has been a recent upswell in the number and quality of investigations, affording tentative conclusions about the roles of HCs in spatial cognition and mental health, particularly depression. Thus, this paper leverages findings from the past few years to highlight the heterogeneous aspects of use that seem to matter for behavior - ranging from variation in hormonal contraceptive formulations and routes of administration to individual differences among users linked to age and reproductive health history. This paper closes with five tips for future research that will help capture and clarify heterogeneity in potential relations between HCs and behavior, namely data collection, regional access, lifespan factors, gender, and collaboration. HCs are sociopolitically provocative and research on their potential behavioral neuroendocrine impacts is becoming increasingly popular. It is, therefore, imperative for scientists to conduct replicable and robust empirical investigations, and to communicate findings with the nuance that the heterogeneity among users and effects requires.

Reproductive hormones in relation to white matter hyperintensity volumes among midlife women.

INTRODUCTION: Although reproductive hormones are implicated in cerebral small vessel disease in women, few studies consider measured hormones in relation to white matter hyperintensity volume (WMHV), a key indicator of cerebral small vessel disease. Even fewer studies consider estrone (E1), the primary postmenopausal estrogen, or follicle-stimulating hormone (FSH), an indicator of ovarian age. We tested associations of estradiol (E2), E1, and FSH to WMHV among women. METHODS: Two hundred twenty-two women (mean age = 59) underwent hormone assays (E1, E2, FSH) and 3T brain magnetic resonance imaging. Associations of hormones to WMHV were tested with linear regression. RESULTS: Higher E2 (B[standard error (SE)] = -0.17[0.06], P = 0.008) and E1 (B[SE] = -0.26[0.10], P = 0.007) were associated with lower whole-brain WMHV, and higher FSH (B[SE] = 0.26[0.07], P = 0.0005) with greater WMHV (covariates age, race, education). When additionally controlling for cardiovascular disease risk factors, associations of E1 and FSH to WMHV remained. DISCUSSION: Reproductive hormones, particularly E1 and FSH, are important to women's cerebrovascular health. HIGHLIGHTS: Despite widespread belief that sex hormones are important to women's brain health, little work has considered how these hormones in women relate to white matter hyperintensities (WMH), a major indicator of cerebral small vessel disease. We considered relations of estradiol (E2), estrone (E1), and follicle-stimulating hormone (FSH) to WMH in midlife women. Higher E2 and E1 were associated with lower whole-brain WMH volume (WMHV), and higher FSH with higher whole-brain WMHV. Associations of E1 and FSH, but not E2, to WMHV persisted with adjustment for cardiovascular disease risk factors. Findings underscore the importance of E2 and FSH to women's cerebrovascular health.

Endocrine Entropy.

This communication defines and describes the novel concept of endocrine entropy. The authors share insights regarding the various facets of entropy in endocrine epidemiology, physiology, clinical presentation and management. The discussion opens up a new way of approaching endocrinology. Recent advances in artificial intelligence, assessment and addressal of entropy may become integral part of endocrine diagnostics and therapeutics.

Endocrine Entropy.

This communication defines and describes the novel concept of endocrine entropy. The authors share insights regarding the various facets of entropy in endocrine epidemiology, physiology, clinical presentation and management. The discussion opens up a new way of approaching endocrinology. Recent advances in artificial intelligence, assessment and addressal of entropy may become integral part of endocrine diagnostics and therapeutics.

Effect of saponins in Panax notoginseng (Burkill) F. H. Chen on the steroid hormone levels in the chronic unpredictable mild stress model of depression in rats.

Recent research has indicated that Panax notoginseng saponins (PNS) extracted from the radix of Panax notoginseng (Burkill) F. H. Chen exert antidepressant effects. This study aimed to assess the antidepressive effects of ginsenoside Rg1 and PNS in a depression model induced by chronic unpredictable mild stress (CUMS). Over a period of three weeks, rats were administered ginsenoside Rg1 at a dose of 30 mg/kg and PNS at dosages ranging from 100 to 200 mg/kg body weight per day. To assess how ginsenoside Rg1 and PNS influence depression-like behaviours in rats, various assessments were conducted, including coat state evaluation, forced swim test, and elevated plus maze test. The levels of cortisol and testosterone in serum samples were analysed using the liquid chromatography-electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS) method. LC-ESI-MS/MS method provides precise and accurate results. The lower limit of quantification values for cortisol and testosterone were determined as 100 and 2 pg/mL, respectively. Our data demonstrated that both ginsenoside Rg1 and PNS significantly reversed depression-like behaviour in rats by improving coat condition, reducing immobility time in the forced swim test, and increasing time spent in the open arms of the elevated plus maze test. Furthermore, ginsenoside Rg1 and PNS exhibited a regulatory effect on cortisol and testosterone levels in plasma. These findings suggest that ginsenoside Rg1 and PNS may be potential antidepressants in clinical treatment.

Fisetin ameliorates polycystic ovary syndrome in rats via a mechanistic modulation of AMP-activated protein kinase and SIRT1 molecular pathway.

Fisetin, a polyphenolic flavonoid, exhibits numerous pharmacological activities against metabolic syndromes. The present research aims to explore the therapeutic efficacy of fisetin in experimental polycystic ovary syndrome (PCOS). Female Sprague-Dawley rats were administered mifepristone (20 mg/kg/day) to induce PCOS. PCOS rats were treated with fisetin (20 mg/kg and 40 mg/kg) and further compared with metformin HCl, the conventional drug for PCOS. The mechanism of fisetin was explored using dorsomorphin (an AMPK inhibitor). Then, rats were sacrificed for further analysis of biochemical and histological parameters. PCOS rats exhibited irregular estrous cycles, increased serum testosterone (4.72 ± 0.139 ng/ml), estradiol (750.2 ± 16.56 pg/ml), LH (30.33 ± 1.563 mIU/ml), HOMA-IR (1.115 ± 0.049), TNF-α (86.59 ± 3.93 pg/ml), IL-6 (55.34 ± 4.432 pg/ml), and TBARS (3.867 ± 0.193 µmol/mg) along with declined progesterone (11.67 ± 1.54 ng/ml), FSH (13.33 ± 1.256 mIU/ml), GSH (33.47 ± 1.348 µmol/mg) levels, and SOD (2.163 ± 0.298 U/mg) activity as compared to normal control group. Fisetin high dose significantly lowers testosterone (3.014 ± 0.234 ng/ml), estradiol (533.7 ± 15.39 pg/ml), LH (16.67 ± 1.62 mIU/ml), HOMA-IR (0.339 ± 0.20), TNF-α (46.02 ± 2.66 pg/ml), IL-6 (31.77 ± 3.47 pg/ml), and TBARS (1.747 ± 0.185 µmol/mg) and enhances progesterone (33.17 ± 1.447 ng/ml), FSH (27.17 ± 1.42 mIU/ml), GSH (60.35 ± 1.1.102 µmol/mg) levels, and SOD (4.513 ± 0.607 U/mg) activity. The histology of ovarian tissues shows a significant increase in cystic follicles in PCOS rats compared with the normal control group. These alterations were attenuated with fisetin treatment. Administration of dorsomorphin with fisetin can reverse the beneficial effects of fisetin in PCOS rats. Altogether, these present findings highlight the potential of fisetin as a promising therapeutic intervention for the management of PCOS by modulating AMPK/SIRT1 signaling in rats.

Genome-wide identification and expression analysis of histone deacetylase and histone acetyltransferase genes in response to drought in poplars.

BACKGROUND: Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are involved in plant growth and development as well as in response to environmental changes, by dynamically regulating gene acetylation levels. Although there have been numerous reports on the identification and function of HDAC and HAT in herbaceous plants, there are fewer report related genes in woody plants under drought stress. RESULTS: In this study, we performed a genome-wide analysis of the HDAC and HAT families in Populus trichocarpa, including phylogenetic analysis, gene structure, conserved domains, and expression analysis. A total of 16 PtrHDACs and 12 PtrHATs were identified in P. trichocarpa genome. Analysis of cis-elements in the promoters of PtrHDACs and PtrHATs revealed that both gene families could respond to a variety of environmental signals, including hormones and drought. Furthermore, real time quantitative PCR indicated that PtrHDA906 and PtrHAG3 were significantly responsive to drought. PtrHDA906, PtrHAC1, PtrHAC3, PtrHAG2, PtrHAG6 and PtrHAF1 consistently responded to abscisic acid, methyl jasmonate and salicylic acid under drought conditions. CONCLUSIONS: Our study demonstrates that PtrHDACs and PtrHATs may respond to drought through hormone signaling pathways, which helps to reveal the hub of acetylation modification in hormone regulation of abiotic stress.

Genome-wide identification, characterization, and evolutionary analysis of the barley TALE gene family and its expression profiles in response to exogenous hormones.

Three-amino-loop-extension (TALE) family belongs to the homeobox gene superfamily and occurs widely in plants, playing a crucial role in regulating their growth and development. Currently, genome-wide analysis of the TALE family has been completed in many plants. However, the systematic identification and hormone response analysis of the TALE gene family in barley are still lacking. In this study, 21 TALE candidate genes were identified in barley, which can be divided into KNOX and BELL subfamilies. Barley TALE members in the same subfamily of the phylogenetic tree have analogically conserved motifs and gene structures, and segmental duplications are largely responsible for the expansion of the HvTALE family. Analysis of TALE orthologous and homologous gene pairs indicated that the HvTALE family has mainly undergone purifying selective pressure. Through spatial structure simulation, HvKNOX5-HvKNOX6 and HvKNOX5-HvBELL11 complexes are all formed through hydrogen bonding sites on both the KNOX2 and homeodomain (HD) domains of HvKNOX5, which may be essential for protein interactions among the HvTALE family members. Expression pattern analyses reveal the potential involvement of most HvTALE genes in responses to exogenous hormones. These results will lay the foundation for regulation and function analyses of the barley TALE gene family in plant growth and development by hormone regulation.

Effects of antenatal corticosteroids on fetal hemodynamics: a longitudinal study.

Objective: To study the effect of antenatal corticosteroid administration on fetal hemodynamics using longitudinal analysis of Doppler waveforms in the umbilical artery (UA) and middle cerebral artery (MCA). Materials and Methods: This was a retrospective study that included 30 fetuses at risk for preterm birth. Twenty-eight pregnant women were treated with betamethasone for fetal lung maturation. Doppler examinations of the UA and MCA were performed once before and three or eight times after corticosteroid administration. We used a Bayesian hierarchical linear model. Reference ranges were constructed, and associations between variables (gestational age and pre-eclampsia) were tested. Results: The mean maternal age, gestational age at betamethasone administration, and gestational age at delivery were 32.6 ± 5.89 years, 30.2 ± 2.59 weeks, and 32.9 ± 3.42 weeks, respectively. On UA Doppler, there was a significant decrease in the pulsatility index (PI) after corticosteroid administration, with a mean of 0.1147 (credibility interval: 0.03687-0.191) in three observations and a median of 0.1437 (credibility interval: 0.02509-0.2627) in eight observations. However, there was no significant change in the Doppler MCA PI, regardless of gestational age and the presence or absence of pre-eclampsia. Conclusion: Although antenatal corticosteroid administration induced a significant decrease in the Doppler UA PI, we observed no change in the cerebral vasculature.

Objetivo: Estudar o efeito da administração antenatal de corticosteroides na hemodinâmica fetal mediante análise longitudinal do Doppler na artéria umbilical (AU) e artéria cerebral média (ACM). Materiais e Métodos: Este foi um estudo retrospectivo que incluiu 30 fetos com risco de nascimento pré-termo. Vinte e oito gestantes foram tratadas com betametasona para maturação pulmonar fetal. Os exames de Doppler da AU e da ACM foram realizados uma vez antes e depois da administração de corticosteroides, num total de três ou oito observações. Utilizamos o modelo linear hierárquico com abordagem Bayesiana. Foram construídos os intervalos de referência e testadas associações entre variáveis (idade gestacional e pré-eclâmpsia). Resultados: A média ± desvio-padrão da idade materna, idade gestacional na administração de betametasona e idade gestacional no parto foram 32,6 ± 5,89 anos, 30,2 ± 2,59 semanas e 32,9 ± 3,42 semanas, respectivamente. No Doppler da AU, verificou-se diminuição significativa do índice de pulsatilidade (IP) com a terapêutica com corticosteroides (média: 0,1147 [0,03687-0,191]; em três observações) (mediana: 0,1437 [0,02509-0,2627]; em oito observações). No entanto, não foi observada alteração significativa no IP do Doppler da ACM, independentemente da idade gestacional e do diagnóstico de pré-eclâmpsia. Conclusão: Os corticosteroides pré-natais induziram diminuição significativa no IP do Doppler da AU, mas não houve alteração na vasculatura cerebral.

The influence of sex-specific factors on biological transformations and health outcomes in aging processes.

The aging process demonstrates notable differences between males and females, which are key factors in disease susceptibility and lifespan. The differences in sex chromosomes are fundamental to the presence of sex bias in organisms. Moreover, sex-specific epigenetic modifications and changes in sex hormone levels impact the development of immunity differently during embryonic development and beyond. Mitochondria, telomeres, homeodynamic space, and intestinal flora are intricately connected to sex differences in aging. These elements can have diverse effects on men and women, resulting in unique biological transformations and health outcomes as they grow older. This review explores how sex interacts with these elements and shapes the aging process.

The role of drought response genes and plant growth promoting bacteria on plant growth promotion under sustainable agriculture: A review.

Drought is a major stressor that poses significant challenges for agricultural practices. It becomes difficult to meet the global demand for food crops and fodder. Plant physiology, physico-chemistry and morphology changes in plants like decreased photosynthesis and transpiration rate, overproduction of reactive oxygen species, repressed shoot and root shoot growth and modified stress signalling pathways by drought, lead to detrimental impacts on plant development and output. Coping with drought stress requires a variety of adaptations and mitigation techniques. Crop yields could be effectively increased by employing plant growth-promoting rhizobacteria (PGPR), which operate through many mechanisms. These vital microbes colonise the rhizosphere of crops and promote drought resistance by producing exopolysaccharides (EPS), 1-aminocyclopropane-1-carboxylate (ACC) deaminase and phytohormones including volatile compounds. The upregulation or downregulation of stress-responsive genes causes changes in root architecture due to acquiring drought resistance. Further, PGPR induces osmolyte and antioxidant accumulation. Another key feature of microbial communities associated with crops includes induced systemic tolerance and the production of free radical-scavenging enzymes. This review is focused on detailing the role of PGPR in assisting plants to adapt to drought stress.

Phthalate exposure during pregnancy and its association with thyroid hormones: A prospective cohort study.

Phthalate esters (PAEs) possess endocrine-disrupting properties. Studies in humans have indicated that in utero phthalate exposure affects maternal thyroid hormones, which are essential for fetal growth and development. However, these studies also reported inconsistent results on the relationship between phthalates and thyroid hormones. This prospective cohort study aimed to assess phthalate exposure across the three trimesters of pregnancy and its association with thyroid hormone levels. From 2019 to 2022, we recruited 672 pregnant women, and two urine samples and one blood sample were collected from each participant during the pregnancy. We examined the urine samples from 663, 335, and 294 women in the first, second, and third trimester, respectively, for the following seven phthalate metabolites: monoethyl phthalate (MEP) from diethyl phthalate (DEP); mono-n-butyl phthalate (MnBP) and mono-iso-butyl phthalate (MiBP) from dibutyl phthalate (DBP); monobenzyl phthalate (MBzP) from butyl benzyl phthalate; and three di(2-ethylhexyl) phthalate (DEHP) metabolites, mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP). Additionally, we examined the levels of free thyroxine (FT4), thyroid-stimulating hormone (TSH), and total triiodothyronine (TT3) in the serum samples of the following participants: 596, 627, and 576 in the first trimester; 292, 293, and 282 in the second trimester; and 250, 250, and 248 in the third trimester, respectively. Other than MBzP, which was detected in 25%-33% of the samples, other metabolites were detectable in >86% of urine samples, indicating widespread exposure to DEP, DBP, and DEHP. The detected phthalate exposure levels in our cohort were significantly higher than those reported in other countries. Metabolite levels varied across the trimesters, implying changes in exposure and metabolism throughout pregnancy. The observed variability in urinary concentrations of phthalate metabolites, which ranged from poor to moderate, underscores the importance of taking multiple measurements during pregnancy for precise exposure assessment. Using a linear mixed model, we analyzed the effects of repeated phthalate exposure on thyroid hormone levels while adjusting for potential confounders. We observed significant linear trends in FT4, TSH, and, to a lesser extent, TT3 across quartiles of specific phthalate metabolites. Comparing the highest to the lowest quartiles, we found a significant increase in FT4 levels, ranging from 2 to 3.7%, associated with MEP; MECPP; MEHHP; and the sum of seven metabolites (∑7PAE), three DEHP metabolites (∑3DEHP), two DBP metabolites (∑DBP), and both low molecular weight (∑LMW) and high molecular weight metabolites. Increased TSH levels (5%-16%) were observed for all phthalate metabolites (except MEHHP) and their molar sums, including ∑7PAE. For TT3, a significant increase was observed with MEP (2.2%) and a decrease was observed with ∑DBP (-2.7%). A higher TSH/FT4 ratio was observed with the highest quartiles (third or fourth) of several phthalate metabolites: MEP (8.8%), MiBP (8.7%), MnBP (22.2%), ∑7PAE (15.3%), ∑DBP (16.4%), and ∑LMW (18.6%). These hormonal alterations, most notably in the second and third trimesters, suggest that phthalate exposure may impact fetal growth and development by affecting maternal thyroid function.