Dataset Information

Effect of sex-specific differences on function of induced hepatocyte-like cells generated from male and female mouse embryonic fibroblasts.

ABSTRACT:

Background

The liver is one of the vital organs involved in detoxification and metabolism. The sex-based differences between the functionality of male and female liver have been previously reported, i.e., male's liver are good in alcohol clearance and lipid metabolism, while female's liver are better in cholesterol metabolism. To date, studies on novel drug toxicity have not considered the sex-specific dimorphic nature of the liver. However, the use of hepatocyte-like cells to treat liver diseases has increased recently.

Methods

Mouse embryos were isolated from a pregnant female C57BL/6J mouse where mouse embryonic fibroblasts (MEFs) were isolated from back skin tissue of each embryo. MEFs were transduced with human transcription factors hHnf1?, hHnf4?, and hFoxa3 using the lentiviral system. The transduced MEFs were further treated with hepatocyte-conditioned media followed by its analysis through RT-qPCR, immunofluorescence, functional assays, and finally whole-transcriptome RNA sequencing analysis. For in vivo investigation, the mouse hepatocyte-like cells (miHep) were transplanted into CCl4-induced acute liver mouse model.

Results

In this study, we evaluated the sex-specific effect of miHep induced from male- and female-specific mouse embryonic fibroblasts (MEFs). We observed miHeps with a polygonal cytoplasm and bipolar nucleus and found that male miHeps showed higher mHnf4a, albumin secretion, and polyploidization than female miHeps. Transcriptomes from miHeps were similar to those from the liver, especially for Hnf4a of male miHeps. Male Cyps were normalized to those from females, which revealed Cyp expression differences between liver and miHeps. In both liver and miHeps, Cyp 4a12a and Cyp 4b13a/2b9 predominated in males and females, respectively. After grafting of miHeps, AST/ALT decreased, regardless of mouse sex.

Conclusion

In conclusion, activation of endogenic Hnf4a is important for generation of successful sex-specific miHeps; furthermore, the male-derived miHep exhibits comparatively enhanced hepatic features than those of female miHep.

SUBMITTER: Ullah I

PROVIDER: S-EPMC7831237 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Effect of sex-specific differences on function of induced hepatocyte-like cells generated from male and female mouse embryonic fibroblasts.

Ullah Imran I Shin Yurianna Y Kim Yeongji Y Oh Keon Bong KB Hwang Seongsoo S Kim Young-Im YI Lee Jeong Woong JW Hur Tai-Young TY Lee Seunghoon S Ock Sun A SA

Stem cell research & therapy 20210125 1

<h4>Background</h4>The liver is one of the vital organs involved in detoxification and metabolism. The sex-based differences between the functionality of male and female liver have been previously reported, i.e., male's liver are good in alcohol clearance and lipid metabolism, while female's liver are better in cholesterol metabolism. To date, studies on novel drug toxicity have not considered the sex-specific dimorphic nature of the liver. However, the use of hepatocyte-like cells to treat live ...[more]

PMID: 33494802

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Project description:ImportanceStudies have found that female surgeons have fewer opportunities to perform highly remunerated operations, a circumstance that contributes to the sex-based pay gap in surgery. Procedures performed by surgeons are, in part, determined by the referrals they receive. In the US and Canada, most practicing physicians who provide referrals are men. Whether there are sex-based differences in surgical referrals is unknown.ObjectiveTo examine whether physicians' referrals to surgeons are influenced by the sex of the referring physician and/or surgeon.Design, setting, and participantsThis cross-sectional, population-based study used administrative databases to identify outpatient referrals to surgeons in Ontario, Canada, from January 1, 1997, to December 31, 2016, with follow-up to December 31, 2018. Data analysis was performed from April 7, 2019, to May 14, 2021.ExposuresReferring physician sex.Main outcomes and measuresThis study compared the proportion of referrals (overall and those referrals that led to surgery) made by male and female physicians to male and female surgeons to assess associations between surgeon, referring physician, or patient characteristics and referral decisions. Discrete choice modeling was used to examine the extent to which sex differences in referrals were associated with physicians' preferences for same-sex surgeons.ResultsA total of 39 710 784 referrals were made by 44 893 physicians (27 792 [61.9%] male) to 5660 surgeons (4389 [77.5%] male). Female patients made up a greater proportion of referrals to female surgeons than to male surgeons (76.8% vs 55.3%, P < .001). Male surgeons accounted for 77.5% of all surgeons but received 87.1% of referrals from male physicians and 79.3% of referrals from female physicians. Female surgeons less commonly received procedural referrals than male surgeons (25.4% vs 33.0%, P < .001). After adjusting for patient and referring physician characteristics, male physicians referred a greater proportion of patients to male surgeons than did female physicians; differences were greatest among referrals from other surgeons (rate ratio, 1.14; 95% CI, 1.13-1.16). Female physicians had a 1.6% (95% CI, 1.4%-1.9%) greater odds of same-sex referrals, whereas male physicians had a 32.0% (95% CI, 31.8%-32.2%) greater odds of same-sex referrals; differences did not attenuate over time.Conclusions and relevanceIn this cross-sectional, population-based study, male physicians appeared to have referral preferences for male surgeons; this disparity is not narrowing over time or as more women enter surgery. Such preferences lead to lower volumes of and fewer operative referrals to female surgeons and are associated with sex-based inequities in medicine.

Project description:AimsFirst, to discuss sex differences in auditory function between women and men, and whether cyclic fluctuations in levels of female sex hormones (i.e., estradiol and progesterone) affect auditory function in pre-menopausal and post-menopausal women. Second, to systematically review the literature concerning the discussed patterns in order to give an overview of the methodologies used in research. Last, to identify the gap in knowledge and to make recommendations for future work.Methods for the systematic reviewPopulation, Exposure, Control, Outcome and Study design (PECOS) criteria were used in developing the review questions. The review protocol follows the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was pre-registered in the Prospective Register of Systematic Reviews (PROSPERO; CRD42020201480). Data Sources: EMBASE, PubMed, MEDLINE (Ovid), PsycINFO, ComDisDome, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL) via Cochrane Library, and scanning reference lists of relevant studies, and internet resources (i.e., Mendeley) were used. Only studies published between 1999 and 2022, in English, or in English translation, were included. The quality of evidence was assessed using the Newcastle-Ottawa Scale (NOS).ResultsSex differences: Women had more sensitive hearing (measured at the level of peripheral and central auditory system) than men. Cyclic fluctuations: Auditory function in women fluctuated during the menstrual cycle, while no such fluctuations in men over the same time period were reported. Hearing sensitivity improved in women during the late follicular phase, and decrease during the luteal phase, implying an effect of female sex hormones, although the specific effects of estradiol and progesterone fluctuations on the central auditory system remain unclear. Hearing sensitivity in women declined rapidly at the onset of menopause.ConclusionThe review has shown the following. Consistent sex differences exist in auditory function across the auditory pathway with pre-menopausal women often showing better function than age-matched men. Moreover, pre-menopausal women show fluctuations in hearing function across the menstrual cycle with a better function during the peak of estradiol or when the ratio of estradiol to progesterone is high. Third, menopause marks the onset of hearing loss in women, characterized by a rapid decline in hearing sensitivity and a more pronounced loss than in age-matched men. Finally, the systematic review highlights the need for well-designed and -controlled studies to evaluate the influence of estradiol and progesterone on hearing by consistently including control groups (e.g., age-matched man), using objective tests to measure hormonal levels (e.g., in saliva or blood), and by testing participants at different points across the menstrual cycle.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020201480, identifier CRD42020201480.

Dataset Information

Effect of sex-specific differences on function of induced hepatocyte-like cells generated from male and female mouse embryonic fibroblasts.

Background

Methods

Results

Conclusion

Publications

Effect of sex-specific differences on function of induced hepatocyte-like cells generated from male and female mouse embryonic fibroblasts.

Similar Datasets

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