Natural Physiological Changes During Pregnancy.

Pregnancy causes physiological changes that support the growing fetus and get the mother ready for labor and delivery. Some of these modifications affect biochemical levels; they are normally stable, while others could imitate symptoms of illness. It is critical to distinguish between pathology associated with disease and typical physiological changes. This review article focuses on the significant changes that occur throughout a typical pregnancy.

Pregnancy-responsive pools of adult neural stem cells for transient neurogenesis in mothers.

Adult neural stem cells (NSCs) contribute to lifelong brain plasticity. In the adult mouse ventricular-subventricular zone, NSCs are heterogeneous and, depending on their location in the niche, give rise to different subtypes of olfactory bulb (OB) interneurons. Here, we show that multiple regionally distinct NSCs, including domains that are usually quiescent, are recruited on different gestation days during pregnancy. Synchronized activation of these adult NSC pools generates transient waves of short-lived OB interneurons, especially in layers with less neurogenesis under homeostasis. Using spatial transcriptomics, we identified molecular markers of pregnancy-associated interneurons and showed that some subsets are temporarily needed for own pup recognition. Thus, pregnancy triggers transient yet behaviorally relevant neurogenesis, highlighting the physiological relevance of adult stem cell heterogeneity.

Giving birth gives birth to neurons.

In mice, pregnancy results in new neurons that support recognition of pups.

Barriers to progress in pregnancy research: How can we break through?

Healthy pregnancies are fundamental to healthy populations, but very few therapies to improve pregnancy outcomes are available. Fundamental concepts-for example, placentation or the mechanisms that control the onset of labor-remain understudied and incompletely understood. A key issue is that research efforts must capture the complexity of the tripartite maternal-placental-fetal system, the dynamics of which change throughout gestation. Studying pregnancy disorders is complicated by the difficulty of creating maternal-placental-fetal interfaces in vitro and the uncertain relevance of animal models to human pregnancy. However, newer approaches include trophoblast organoids to model the developing placenta and integrated data-science approaches to study longer-term outcomes. These approaches provide insights into the physiology of healthy pregnancy, which is the first step to identifying therapeutic targets in pregnancy disorders.

Application of Life's Essential 8 to assess cardiovascular health during early childhood.

PURPOSE: Assess cardiovascular health (CVH) during early childhood using the American Heart Association's recently updated construct, Life's Essential 8 (LE8); examine concordance in CVH status per LE8 versus Life's Simple 7 (LS7); and identify perinatal correlates of high CVH per LE8. METHODS: We applied LE8 and LS7 to data from 305 children aged 4-7 years in Denver, CO; estimated % low, moderate, high, and optimal CVH; assessed concordance in CVH status based on LE8 and LS7 using contingency tables; and used multivariable logistic regression to identify early-life correlates of high CVH per LE8. RESULTS: Average age of children was 4.7 ± 0.6 years, 44.6% were female. No participants had low or optimal CVH, 43.9% had high, and 56.1% had moderate CVH per LE8, whereas 33.4% had high and 66.6% had moderate CVH per LS7. Twenty-two percent had high CVH based on both constructs. Correlates of high CVH were maternal prenatal diet quality (odds ratioHealthy Eating Index score>vs. ≤57 = 1.90 [1.12, 3.21]) and child age (odds ratioper 1 year = 1.58 [1.04. 2.42]). CONCLUSIONS: LE8 yielded higher prevalence of high CVH than LS7 during early childhood, though there is modest concordance between the two constructs. Maternal diet is a potential modifiable target to optimize early-life CVH.

Effect of Pregnancy in 42 Elite to World-Class Runners on Training and Performance Outcomes.

PURPOSE: The International Olympic Committee expert group on pregnancy has identified a paucity of information regarding training and performance in truly elite athletes. Thus, the purpose of this study was to quantify elite runners' training volume throughout pregnancy and postpartum competition performance outcomes. METHODS: Forty-two elite (>50% competed at the World Championships/Olympic) middle-/long-distance runners' training before, during, and after pregnancy (quality/quantity/type) data (retrospective questionnaire) and competition data (published online) were collected. RESULTS: Running volume decreased significantly ( P < 0.01) from the first trimester (63 ± 34 km·wk -1 ) to the third trimester (30 ± 30 km·wk -1 ). Participants returned to activity/exercise at ~6 wk postpartum and to 80% of prepregnancy training volumes by 3 months. Participants who intended to return to equivalent performance levels postpregnancy, there was no statistical decrease in performance in the 1 to 3 yr postpregnancy compared with prepregnancy, and ~56% improved performances postpregnancy. CONCLUSIONS: This study features the largest cohort of elite runners training and competition outcomes assessed throughout pregnancy, with training volumes being approximately two to four times greater than current guidelines. For the first time, performance was directly assessed (due to the quantifiable nature of elite running), and study participants who intended to return to high-level competition did so at a statistically similar level of performance in the 1- to 3-yr period postpregnancy. Taken together, this article provides much needed insights into current training practices and performance of elite pregnant runners, which should help to inform future training guidelines as well as sport policy and sponsor expectations around return to training timelines and performance.

Multiscale model of heart growth during pregnancy: integrating mechanical and hormonal signaling.

Pregnancy stands at the interface of mechanics and biology. The growing fetus continuously loads the maternal organs as circulating hormone levels surge, leading to significant changes in mechanical and hormonal cues during pregnancy. In response, maternal soft tissues undergo remarkable growth and remodeling to support the mother and baby for a healthy pregnancy. We focus on the maternal left ventricle, which increases its cardiac output and mass during pregnancy. This study develops a multiscale cardiac growth model for pregnancy to understand how mechanical and hormonal cues interact to drive this growth process. We coupled a cell signaling network model that predicts cell-level hypertrophy in response to hormones and stretch to a compartmental model of the rat heart and circulation that predicts organ-level growth in response to hemodynamic changes. We calibrated this multiscale model to data from experimental volume overload and hormonal infusions of angiotensin 2 (AngII), estrogen (E2), and progesterone (P4). We then validated the model's ability to capture interactions between inputs by comparing model predictions against published observations for the combinations of VO + E2 and AngII + E2. Finally, we simulated pregnancy-induced changes in hormones and hemodynamics to predict heart growth during pregnancy. Our model produced growth consistent with experimental data. Overall, our analysis suggests that the rise in P4 during the first half of gestation is an important contributor to heart growth during pregnancy. We conclude with suggestions for future experimental studies that will provide a better understanding of how hormonal and mechanical cues interact to drive pregnancy-induced heart growth.

Levels of blood pressure, cardiovascular biomarkers and their correlations in women with previous pre-eclamptic pregnancy within 7 years postpartum: a cross-sectional study in Thailand.

OBJECTIVE: To assess the levels of blood pressure, cardiovascular biomarkers and their correlations measured within 7 years postpartum in women with previous pre-eclamptic pregnancies compared with women with previous normotensive pregnancies. DESIGN: Cross-sectional study. SETTING: Two tertiary hospitals in the southern region of Thailand. PARTICIPANTS: Women with pre-eclamptic and normotensive pregnancies in the past 7 years were enrolled from 1 October 2019 to 30 April 2021. Eligible women were interviewed, examined for body mass index (BMI) and blood pressure, and donated morning spot urine and blood samples. PRIMARY OUTCOME MEASURES: Serum high-sensitivity C reactive protein, creatinine, fasting blood glucose (FBS), glycated haemoglobin (HbA1c), low-density lipoprotein (LDL) cholesterol, urine microalbumin to creatinine ratio (UACR) and sodium were measured. Group differences in biomarkers were tested using unpaired t-test, Wilcoxon rank-sum test or χ2 test. The levels of blood pressure and biomarkers between the two study groups at <2 years, 2-4 years and >4 years were also compared. The correlations between blood pressure and biomarkers were analysed using Pearson's correlation and partial correlation methods. RESULTS: From 206 women included in the analysis, 88 had pre-eclamptic pregnancies and 118 had normotensive pregnancies. Compared with women with previous normotensive pregnancies, women with previous pre-eclamptic pregnancies had significantly increased rates of hypertension (31.8% vs 7.6%, p<0.001) and obesity (55.7% vs 40.7%, p=0.038), as well as higher serum levels of FBS (p<0.001), HbA1c (p<0.001), LDL cholesterol (p=0.03), creatinine (p<0.001) and UACR (p<0.001). Correlation coefficients of BMI, serum creatinine and UACR with blood pressure ranged from 0.27 to 0.31. CONCLUSION: The risk of hypertension after a pre-eclamptic pregnancy increased. Blood pressure measurement combined with BMI, serum creatinine and UACR screening at least once during 7 years postpartum is suggested for early detection of cardiovascular risk.

Prolactin and its significance in the placenta.

Prolactin, a pituitary hormone that was discovered about 80 years ago and is primarily known for its functions in mammary gland development and lactation, is now known to participate in numerous functions across different phylogenetic groups. Fundamentally known for its secretion from lactotroph cells in adenohypophysis region of pituitary gland, newer studies have demonstrated a number of extrapituitary sites which secrete prolactin, where it acts in an autocrine, paracrine, and endocrine manner to regulate essential physiological and biochemical processes. These sites include lymphocytes, epithelial cells of lactating mammary glands, breast cancer cells of epithelial origin, and the placenta. The placenta is one of the most important organs secreting prolactin; however, its role in placental biology has not to date been reviewed comprehensively. This review elaborates upon the various facets of prolactin hormone, including prolactin production and its post-translational modifications and signaling. Major emphasis is placed on placental prolactin and its potential roles, ranging from the role of prolactin in angiogenesis, preeclampsia, maternal diabetes, and anti-apoptosis, among others.

Gene Expression of Pregnancy Neutrophils Differs for Protease versus Lipopolysaccharide Stimulation.

Neutrophils, which extensively infiltrate maternal systemic blood vessels in preeclampsia, express protease-activated receptor 1 (PAR-1) but only during pregnancy. Neutrophils are generally considered to be non-specific in their response, but the pregnancy-specific expression of PAR-1 could result in a gene expression profile unique to pregnancy, which could help explain why the maternal inflammatory response in preeclampsia is systemic rather than localized. We sought to determine if gene expression of pregnancy neutrophils would differ if stimulated by a protease versus bacterial lipopolysaccharide (LPS). We isolated neutrophils from normal pregnant women at 30 weeks' gestation and cultured them with elastase or LPS. We used elastase because it is a protease elevated in women with preeclampsia, and it activates pregnancy neutrophils via PAR-1. RNA was isolated from the neutrophils for sequencing of the transcriptomes. We discovered many differences in the gene expression profiles. For example, exposure to elastase resulted in three times more uniquely expressed genes than LPS, and the number of significantly differentially upregulated and downregulated genes was greater for elastase. Analysis of canonical pathways revealed similarities for innate immunity but also differences. LPS treatment enriched more pathways, but elastase activated more genes in each pathway. Elastase treatment enriched the MAPK signaling pathway, whereas LPS did not. This is significant because MAPK is a key mediator of transcriptional responses. These findings indicate that protease stimulation of pregnancy neutrophils results in a different profile than stimulation with LPS, which may help explain why the sterile inflammatory response of preeclampsia is systemic and unique to pregnancy.

Cell-Specific Expression Pattern of Toll-Like Receptors and Their Roles in Animal Reproduction.

Toll-like receptors (TLRs), a part of the innate immune system, have critical roles in protection against infections and involve in basic pathology and physiology. Secreted molecules from the body or pathogens could be a ligand for induction of the TLR system. There are many immune and non-immune types of cells that express at a least single TLR on their surface or cytoplasm. Those cells may be a player in a defense system or in the physiological regulation mechanisms. Reproductive tract and organs contain different types of cells that have essential functions such as hormone production, providing an environment for embryo/fetus, germ cell production, etc. Although lower parts of reproductive organs are in a relationship with outsider contaminants (bacteria, viruses, etc.), upper parts should be sterile to provide a healthy pregnancy and germ cell production. In those areas, TLRs bear controller or regulator roles. In this chapter, we will provide current information about physiological functions of TLR in the cells of the reproductive organs and tract, and especially about their roles in follicle selection, maturation, follicular atresia, ovulation, corpus luteum (CL) formation and regression, establishment and maintenance of pregnancy, sperm production, maturation, capacitation as well as the relationship between TLR polymorphism and reproduction in domestic animals. We will also discuss pathogen-associated molecular patterns (PAMPs)-induced TLRs that involve in reproductive inflammation/pathology.

Pregnancy tailors endotoxin-induced monocyte and neutrophil responses in the maternal circulation.

OBJECTIVE: To comprehensively characterize monocyte and neutrophil responses to E. coli and its product [lipopolysaccharide (LPS) or endotoxin] in vitro during pregnancy. MATERIAL OR SUBJECTS: Peripheral blood was collected from pregnant women during the third trimester (n = 20) and from non-pregnant women (n = 20). METHODS: The number, phagocytic activity, and reactive oxygen species (ROS) production of peripheral monocytes and neutrophils were investigated using flow cytometry. The phenotypes of peripheral monocytes and neutrophils after acute or chronic LPS stimulation were also determined using flow cytometry. Cytokine profiles were quantified for LPS-stimulated peripheral blood mononuclear cells (PBMCs) and a whole blood TruCulture® system using a multiplex immunoassay. RESULTS: Increased number, phagocytic activity, and ROS production capacity of monocytes and neutrophils were found in pregnant compared to non-pregnant women. Additionally, specific subsets of pro-inflammatory monocytes (IL-6+CD14+ or MIP-1α+CD14+ cells) and neutrophils (IL-1ß+CD15+ or MIP-1ß+CD15+ cells) were increased in pregnant women in response to acute LPS stimulation. Moreover, distinct subsets of intermediate-activated monocytes expressing CD142, IL-6, and IL-1RA were increased in pregnant women upon chronic LPS stimulation. Last, pregnant women displayed a different cytokine profile than non-pregnant women in LPS-stimulated PBMCs and in whole blood. CONCLUSIONS: Pregnancy tailors the immune responses of circulating monocytes and neutrophils to endotoxin, a Gram-negative bacterial product.

Longitudinal surface measurements of human blastocysts show that the dynamics of blastocoel expansion are associated with fertilization method and ongoing pregnancy.

BACKGROUND: Despite all research efforts during this era of novel time-lapse morphokinetic parameters, a morphological grading system is still routinely being used for embryo selection at the blastocyst stage. The blastocyst expansion grade, as evaluated during morphological assessment, is associated with clinical pregnancy. However, this assessment is performed without taking the dynamics of blastocoel expansion into account. Here, we studied the dynamics of blastocoel expansion by comparing longitudinal blastocoel surface measurements using time-lapse embryo culture. Our aim was to first assess if this is impacted by fertilization method and second, to study if an association exists between these measurement and ongoing pregnancy. METHODS: This was a retrospective cohort study including 225 couples undergoing 225 cycles of in vitro fertilization (IVF) treatment with time-lapse embryo culture. The fertilization method was either conventional IVF, intracytoplasmic sperm injection (ICSI) with ejaculated sperm or ICSI with sperm derived from testicular sperm extraction (TESE-ICSI). This resulted in 289 IVF embryos, 218 ICSI embryos and 259 TESE-ICSI embryos that reached at least the full blastocyst stage. Blastocoel surface measurements were performed on time-lapse images every hour, starting from full blastocyst formation (tB). Linear mixed model analysis was performed to study the association between blastocoel expansion, the calculated expansion rate (µm2/hour) and both fertilization method and ongoing pregnancy. RESULTS: The blastocoel of both ICSI embryos and TESE-ICSI embryos was significantly smaller than the blastocoel of IVF embryos (beta -1121.6 µm2; 95% CI: -1606.1 to -637.1, beta -646.8 µm2; 95% CI: -1118.7 to 174.8, respectively). Still, the blastocoel of transferred embryos resulting in an ongoing pregnancy was significantly larger (beta 795.4 µm2; 95% CI: 15.4 to 1575.4) and expanded significantly faster (beta 100.9 µm2/hour; 95% CI: 5.7 to 196.2) than the blastocoel of transferred embryos that did not, regardless of the fertilization method. CONCLUSION: Longitudinal blastocyst surface measurements and expansion rates are promising non-invasive quantitative markers that can aid embryo selection for transfer and cryopreservation. TRIAL REGISTRATION: Our study is a retrospective observational study, therefore trial registration is not applicable.

Physical exercise in pregnancy: benefits, risks and prescription.

OBJECTIVES: The aim of this article is to provide a comprehensive literature review, gathering the strongest evidence about the risks and benefits and the prescription of physical exercise during pregnancy. CONTENT: Regular physical exercise during pregnancy is associated with numerous benefits. In general women are not adequately advised on this matter. Along with their concerns regarding the potential associated risks, it contributes to the abandonment or refusal to start exercising during pregnancy. A systematic review was conducted in MEDLINE including articles considered to have the highest level of scientific evidence. Fifty-seven articles, including 32 meta-analysis, 9 systematic reviews and 16 randomized controlled trials were included in the final literature review. SUMMARY: Exercise can help preventing relevant pregnancy related disorders, such as gestational diabetes, excessive gestational weight gain, hypertensive disorders, urinary incontinence, fetal macrosomia, lumbopelvic pain, anxiety and prenatal depression. Exercise is not related with an increased risk of maternal or perinatal adverse outcomes. Compliance with current guidelines is sufficient to achieve the main benefits, and exercise type and intensity should be based on woman's previous fitness level. OUTLOOK: Exercise in pregnancy is safe for both mother and fetus, contributing to prevent pregnancy related disorders. Exercise type and intensity should be adapted to woman's previous fitness level, medical history and characteristics of the ongoing pregnancy.

Perfil lipídico por trimestres del embarazo en gestantes sanas / Lipid profile by trimesters of pregnancy in healthy pregnant women

Con el objetivo de describir el perfil lipídico por trimestres de gestación en gestantes sanas, se realizó un estudio descriptivo, de corte transversal, el cual se condujo con 40 embarazadas entre 20 y 35 años, de un universo de 110, pertenecientes al policlínico Jimmy Hirzel de Bayamo, Granma, entre enero del 2017 y marzo del 2019. Se determinaron las concentraciones de colesterol total, triglicéridos, HDL-colesterol, LDL-colesterol y VLDL-colesterol. Se utilizó el análisis de varianza de un factor, y la prueba de Tukey de comparación múltiple de parejas de medias. El colesterol, los triglicéridos, el LDL-colesterol y el VLDL-colesterol variaron de forma significativa con el trimestre de gestación. El colesterol total se incrementó en el segundo y tercer trimestre en comparación con el primero, mientras que los triglicéridos, el LDL-colesterol y el VLDL-colesterol se incrementaron en el tercer trimestre en comparación con el primero. El HDL-colesterol no tuvo una variación significativa durante el embarazo. Se concluye que los valores del colesterol total, los triglicéridos, el LDL-colesterol y el VLDL-colesterol varían en relación con el trimestre de la gestación, aumentan de forma significativa en el tercer trimestre en comparación con el primer trimestre del embarazo, en tanto el HDL-colesterol no varía significativamente durante el embarazo(AU)

In order to describe the lipid profile by trimesters of pregnancy in healthy pregnant women, a descriptive, cross-sectional study was conducted with 40 pregnant women between 20 and 35 years of age, from a universe of 110, belonging to the Jimmy Hirzel Hospital in Bayamo, Granma, between January 2017 and March 2019. The concentrations of total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol and VLDL-cholesterol were determined. One-factor analysis of variance was used, and the Tukey's multiple comparison test of pairs of means Cholesterol, triglycerides, LDL-cholesterol, and VLDL-cholesterol varied significantly with gestational trimester total cholesterol increased in the second and third trimesters compared with the first, while triglycerides, LDL-cholesterol and VLDL-cholesterol increased in the third trimester compared to the first. HDL-cholesterol did not have a significant variation time during pregnancy. It is concluded that the values of total cholesterol, triglycerides, LDL-cholesterol and VLDL-cholesterol vary in relation to the trimester of pregnancy, they increase significantly in the third trimester compared to the first trimester of pregnancy, while HDL-cholesterol does not vary significantly during pregnancy(AU)

A prospective study of the relationships between movement and glycemic control during day and night in pregnancy.

Both disturbed sleep and lack of exercise can disrupt metabolism in pregnancy. Accelerometery was used to objectively assess movement during waking (physical activity) and movement during sleeping (sleep disturbance) periods and evaluated relationships with continuous blood glucose variation during pregnancy. Data was analysed prospectively. 15-women without pre-existing diabetes mellitus wore continuous glucose monitors and triaxial accelerometers from February through June 2018 in Sweden. The relationships between physical activity and sleep disturbance with blood glucose rate of change were assessed. An interaction term was fitted to determine difference in the relationship between movement and glucose variation, conditional on waking/sleeping. Total movement was inversely related to glucose rate of change (p < 0.001, 95% CI (- 0.037, - 0.026)). Stratified analyses showed total physical activity was inversely related to glucose rate of change (p < 0.001, 95% CI (- 0.040, - 0.028)), whereas sleep disturbance was not related to glucose rate of change (p = 0.07, 95% CI (< - 0.001, 0.013)). The interaction term was positively related to glucose rate of change (p < 0.001, 95% CI (0.029, 0.047)). This study provides temporal evidence of a relationship between total movement and glycemic control in pregnancy, which is conditional on time of day. Movement is beneficially related with glycemic control while awake, but not during sleep.

El embarazo y los efectos que produce en la salud de las mujeres VIH positivas / Pregnancy and the effects it produces on the health of HIV positive women

INTRODUCCIÓN: Existen 35 millones de casos de infección por el virus de la inmunodeficiencia humana (VIH) en el mundo, y de ellos, 15 millones corresponden a mujeres en edad fértil. El embarazo en las mujeres seropositivas genera efectos relevantes que afectan la condición psicosocial y física. Los cambios que genera el embarazo en una mujer VIH positiva se relacionan con resultados perinatales adversos, como hemorragia posparto, sepsis puerperal, parto prematuro y mortalidad. OBJETIVO: Conocer los efectos físicos y psicosociales que tiene el embarazo en la evolución de la mujer portadora del VIH. MÉTODO: Revisión narrativa. Se realiza un análisis de contenido de fuentes primarias obtenidas mediante búsqueda en las bases de datos CINAHL, PubMed y SciELO. La búsqueda abarcó un periodo de 10 años, en idioma español e inglés. Para la presente investigación se incluyen 22 artículos, de los que se consideraron las secciones de resultados y conclusiones. RESULTADOS: Se seleccionaron inicialmente 318 artículos y 22 fueron elegibles para su inclusión. En esta revisión se plantean tres dimensiones de análisis psicosocial, fisiopatología y características clínicas, y tratamiento farmacológico. La literatura evidencia un efecto psicológico negativo en la población de estudio, y en cuanto al tratamiento se manifiesta un escaso porcentaje de eventos adversos frente a la terapia antirretroviral, por lo que los beneficios superan los riesgos. CONCLUSIONES: Las tres dimensiones planteadas se relacionan entre sí, definiendo los efectos del embarazo en mujeres VIH positivas y lo que conlleva esta condición en la salud de la madre. Se identificaron diversos problemas que afectan la salud de las mujeres seropositiva que se embarazan. Sin embargo, estas mujeres pueden embarazarse siguiendo un tratamiento óptimo, con atenciones de salud en periodos regulares, evitando así la mayoría de los efectos que pueden afectar su salud.

INTRODUCTION: There are 35 million cases of human immunodeficiency virus (HIV) worldwide, 15 million correspond to women of childbearing age. This pregnancy condition in seropositive women generates relevant effects that affect the psychosocial and physical condition. The changes generated by pregnancy in an HIV positive woman are related to adverse perinatal results such as postpartum hemorrhage, puerperal sepsis, premature delivery and mortality. OBJECTIVE: To know the physical and psychosocial effects that pregnancy has on the evolution of women with HIV. METHOD: Narrative review. Content analysis of primary sources obtained through searches in the CINAHL, PubMed and SciELO databases is performed. The search was carried out within a 10-year range, in Spanish and English. For the present investigation 22 articles are included. The sections for the analysis were results and conclusions. RESULTS: 318 articles were initially selected, 22 articles were eligible for inclusion. In this review, three dimensions of psychosocial analysis, pathophysiology and clinical characteristics, and pharmacological treatment are proposed. The literature shows the negative psychological effect in the study population, in terms of treatment there is a low percentage of adverse events compared to ART, so the benefits outweigh the risks. CONCLUSIONS: The three dimensions raised are related to each other, defining the effects of pregnancy in HIV positive women and what the condition entails on the mothers health. Various problems were identified that affect the health of an HIV-positive woman who becomes pregnant. However, these HIV positive women can become pregnant, following optimal treatment, with regular health care, thus avoiding most of the effects that can affect her health.

Pregnancy and weaning regulate human maternal liver size and function.

During pregnancy, the rodent liver undergoes hepatocyte proliferation and increases in size, followed by weaning-induced involution via hepatocyte cell death and stromal remodeling, creating a prometastatic niche. These data suggest a mechanism for increased liver metastasis in breast cancer patients with recent childbirth. It is unknown whether the human liver changes in size and function during pregnancy and weaning. In this study, abdominal imaging was obtained in healthy women at early and late pregnancy and postwean. During pregnancy time points, glucose production and utilization and circulating bile acids were measured. Independently of weight gain, most women's livers increased in size with pregnancy, then returned to baseline postwean. Putative roles for bile acids in liver growth and regression were observed. Together, the data support the hypothesis that the human liver is regulated by reproductive state with growth during pregnancy and volume loss postwean. These findings have implications for sex-specific liver diseases and for breast cancer outcomes.