Dataset Information

Pregnancy and weaning regulate human maternal liver size and function.

ABSTRACT: 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.

SUBMITTER: Q Bartlett A

PROVIDER: S-EPMC8640831 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Pregnancy and weaning regulate human maternal liver size and function.

Q Bartlett Alexandra A Vesco Kimberly K KK Purnell Jonathan Q JQ Francisco Melanie M Goddard Erica E Guan Xiangnan X DeBarber Andrea A Leo Michael C MC Baetscher Eric E Rooney William W Naugler Willscott W Guimaraes Alexander R AR Catalano Patrick P Xia Zheng Z Schedin Pepper P

Proceedings of the National Academy of Sciences of the United States of America 20211101 48

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 l ...[more]

PMID: 34815335

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Project description:The maternal skeleton undergoes dramatic bone loss during pregnancy and lactation, and substantial bone recovery post-weaning. The structural adaptations of maternal bone during reproduction and lactation exert a better protection of the mechanical integrity at the critical load-bearing sites, suggesting the importance of physiological load-bearing in regulating reproduction-induced skeletal alterations. Although it is suggested that physical exercise during pregnancy and breastfeeding improves women's physical and psychological well-being, its effects on maternal bone health remain unclear. Therefore, the objective of this study was to investigate the maternal bone adaptations to external mechanical loading during pregnancy, lactation, and post-weaning recovery. By utilizing an in vivo dynamic tibial loading protocol in a rat model, we demonstrated improved maternal cortical bone structure in response to dynamic loading at tibial midshaft, regardless of reproductive status. Notably, despite the minimal loading responses detected in the trabecular bone in virgins, rat bone during lactation experienced enhanced mechano-responsiveness in both trabecular and cortical bone compartments when compared to rats at other reproductive stages or age-matched virgins. Furthermore, our study showed that the lactation-induced elevation in osteocyte peri-lacunar/canalicular remodeling (PLR) activities led to enlarged osteocyte lacunae. This may result in alterations in interstitial fluid flow-mediated mechanical stimulation on osteocytes and an elevation in solute transport through the lacunar-canalicular system (LCS) during high-frequency dynamic loading, thus enhancing mechano-responsiveness of maternal bone during lactation. Taken together, findings from this study provide important insights into the relationship between reproduction- and lactation-induced skeletal changes and external mechanical loading, emphasizing the importance of weight-bearing exercise on maternal bone health during reproduction and postpartum.

Project description:AIMS:The gut microbiota is believed to play important roles in the health of pregnant mammals, including their nutrient metabolism, immune programming and metabolic regulation. However, until recently, the shifts in gut microbiota composition and faecal and blood metabolic activity during different stages of pregnancy had not been investigated. METHODS AND RESULTS:We investigated the shifts in backfat thickness, plasma and faecal metabolites and gut microbiota on days 30, 60, 90 and 110 of pregnancy and on day 21 after parturition (weaning) in sows. The backfat thickness of sows did not significantly differ among the different stages of pregnancy. The plasma concentrations of lipid metabolites, including triacylglycerol (TG), total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol and calcium were reduced (P < 0·05) during pregnancy. In addition, the concentration of these metabolites, except TG, reached their maximum at the time of weaning. We also found that Tenericutes, Fibrobacteres and Cyanobacteria varied significantly according to the stages of pregnancy in sows (P < 0·05). Most of the genera, such as Clostridiales, Desulfovibrio, Mogibacteriaceae and Prevotella, increased (P < 0·05) with the progression of pregnancy and decreased (P < 0·05) at weaning. The alpha diversity values (i.e., Shannon diversity and observed species) of sow gut microbiota increased (P < 0·05) from pregnancy to weaning. Pregnancy stages also significantly influenced (P < 0·05) the community structure (beta diversity) of gut microbiota. The progression of pregnancy was associated with changes in lipid metabolism and several carbohydrate-degradation bacteria (i.e., Prevotella, Succinivibrio, Bacteroides and Parabacteroides). CONCLUSIONS:Although causal links between the measured parameters remain hypothetical, these findings suggest that the increased diversity and concentration of beneficial gut microbes are associated with the metabolism of pregnant sows. SIGNIFICANCE AND IMPACT OF THE STUDY:Manipulation of the sow gut microbiota composition may potentially influence metabolism and health during pregnancy.

Project description:Background & aimsAlthough worsening liver-related symptoms during pregnancy can occur in primary sclerosing cholangitis (PSC), there are insufficient data to effectively counsel patients on their pre-conception risk and no clear recommendations on monitoring and management during pregnancy. We aimed to describe maternal liver-related symptoms in pregnancy, both before and after PSC diagnosis, and explore factors associated with worsening symptoms and liver-related outcomes.MethodsWe conducted a multicentre retrospective observational study of females with PSC and known pregnancy with live birth, via the International PSC Study Group. We included 450 patients from 12 European centres. Data included clinical variables, liver-related symptoms (pruritus and/or cholangitis) during pregnancy, and liver biochemistry. A composite primary endpoint of transplant-free survival from time of PSC diagnosis was used.ResultsThere were 266 pregnancies in 178 patients following PSC diagnosis. Worsening liver-related symptoms were reported in 66/228 (28.9%) pregnancies; they had a reduced transplant-free survival (p = 0.03), which retained significance on multivariate analysis (hazard ratio 3.02, 95% CI 1.24-7.35; p = 0.02).Abnormal biochemistry and/or liver-related symptoms (pruritus and/or cholangitis) were noted during pregnancy before PSC diagnosis in 21/167 (12.6%) patients. They had a reduced transplant-free survival from pregnancy (p = 0.01), which did not retain significance in a multivariable model (hazard ratio 1.10, 95% CI 0.43-2.85; p = 0.84).ConclusionsLiver-related symptoms are frequently encountered during pregnancies before the diagnosis of PSC, and pregnancy may expose the pre-clinical phase of PSC in some patients. Worsening liver-related symptoms were seen in a third of our cohort with known PSC during pregnancy; and this subgroup had a poorer prognosis, which may be related to more advanced liver disease at time of pregnancy and/or a more severe disease phenotype.Impact and implicationsPatients with PSC can develop worsening of their liver-related symptoms during pregnancy; however, risk factors for this and the long-term implications are not known. We identified that there is a significant risk of these symptoms in pregnancy, both before and after PSC has been diagnosed, particularly in patients with elevated alkaline phosphatase. Furthermore, our findings suggest that worsening symptoms during pregnancy may be associated with adverse long-term clinical outcomes of liver transplantation and death in patients with known PSC. This may be related to the presence of more advanced liver disease at time of pregnancy. This information can be used to counsel patients with PSC before conception and identify patients who need close follow-up after delivery.

Dataset Information

Pregnancy and weaning regulate human maternal liver size and function.

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Pregnancy and weaning regulate human maternal liver size and function.

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