SEARCHOTHERendocrinology, preclinical research

other·endocrinology, preclinical research, nutrition, clinical nutrition, vitamins·PMC10493026

Sex differences in paternal arsenic-induced intergenerational metabolic effects are mediated by estrogen

Cell & Bioscience · 13 authors, 9 centres

AI SUMMARY

FIDELITY 100%

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

“

TL;DR

The sex differences were mediated by circulating estrogen levels and hepatic estrogen receptor signaling.

Full summary

712 CHARS

In contrast, F1 male offspring showed improved glucose tolerance and insulin sensitivity, along with lower liver and blood triglyceride levels. Mechanistic investigations revealed sex-specific hepatic transcriptomic changes. The metabolic phenotypes were linked to disrupted reproductive hormone secretion: F1 females had altered circulating estrogen and follicle-stimulating hormone levels. Limitations include the use of a single arsenic dosage, a mouse model without direct human application, and the focus on paternal effects without exploring maternal exposure. The findings provide mechanistic insights into how paternal environmental exposures can lead to sex-specific intergenerational metabolic effects.

STUDY TYPE

other

SPECIALTY

endocrinology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10493026

Sex differences in paternal arsenic-induced intergenerational metabolic effects are mediated by estrogen

Cell & Bioscience

READ THE FULL PAPER

ABSTRACT

Background Gene-environment interactions contribute to metabolic disorders such as diabetes and dyslipidemia. In addition to affecting metabolic homeostasis directly, drugs and environmental chemicals can cause persistent alterations in metabolic portfolios across generations in a sex-specific manner. Here, we use inorganic arsenic (iAs) as a prototype drug and chemical to dissect such sex differences. Methods After weaning, C57BL/6 WT male mice were treated with 250 ppb iAs in drinking water (iAsF0) or normal water (conF0) for 6 weeks and then bred with 15-week-old, non-exposed females for 3 days in cages with only normal water (without iAs), to generate iAsF1 or conF1 mice, respectively. F0 females and all F1 mice drank normal water without iAs all the time. Results We find that exposure of male mice to 250 ppb iAs leads to glucose intolerance and insulin resistance in F1 female offspring (iAsF1-F), with almost no change in blood lipid profiles. In contrast, F1 males (iAsF1-M) show lower liver and blood triglyceride levels than non-exposed control, with improved glucose tolerance and insulin sensitivity. The liver of F1 offspring shows sex-specific transcriptomic changes, with hepatocyte-autonomous alternations of metabolic fluxes in line with the sex-specific phenotypes. The iAsF1-F mice show altered levels of circulating estrogen and follicle-stimulating hormone. Ovariectomy or liver-specific knockout of estrogen receptor α/β made F1 females resemble F1 males in their metabolic responses to paternal iAs exposure. Conclusions These results demonstrate that disrupted reproductive hormone secretion in alliance with hepatic estrogen signaling accounts for the sex-specific intergenerational effects of paternal iAs exposure, which shed light on the sex disparities in long-term gene-environment interactions. Supplementary Information The online version contains supplementary material available at 10.1186/s13578-023-01121-4.

CITATION EXPORT

Yanfeng Xue, Yingyun Gong, Xin Li et al.. Sex differences in paternal arsenic-induced intergenerational metabolic effects are mediated by estrogen. Cell & Bioscience. (2023). https://doi.org/10.1186/s13578-023-01121-4

AUTHORS

13 · 9 CENTRES

Yanfeng Xue, Yingyun Gong, Xin Li, Fei Peng, Guolian Ding, Zhao Zhang, Junchao Shi, Ilma Saleh Savul, Yong Xu, Qi Chen, Leng Han, Shengyong Mao, Zheng Sun

1https://ror.org/0327f3359grid.411389.60000 0004 1760 4804College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
2https://ror.org/05td3s095grid.27871.3b0000 0000 9750 7019National Center for International Research on Animal Gut Nutrition, Center for Ruminant Nutrition and Feed Technology Research, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
3https://ror.org/02pttbw34grid.39382.330000 0001 2160 926XDivision of Endocrinology, Department of Medicine, Baylor College of Medicine, Houston, TX USA
4https://ror.org/04py1g812grid.412676.00000 0004 1799 0784Department of Endocrinology and Metabolism, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
5https://ror.org/013q1eq08grid.8547.e0000 0001 0125 2443Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
6https://ror.org/03gds6c39grid.267308.80000 0000 9206 2401Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX USA
7grid.223827.e0000 0001 2193 0096Molecular Medicine Program, Department of Human Genetics, and Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT USA
8https://ror.org/02pttbw34grid.39382.330000 0001 2160 926XChildren’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX USA
9https://ror.org/02pttbw34grid.39382.330000 0001 2160 926XDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX USA