肥胖母鼠对雄性子代生殖力的影响及其机制研究

doi:10.3969/j.issn.1004-616x.2023.02.005

Abstract

Abstract: OBJECTIVE： To investigate effects of obese female mice on reproductive ability of male offspring and their possible mechanisms. METHODS： A female mouse obesity model was established by high-fat diet induction for 8 weeks，and caged with normal diet male mice. After birth，the offspring were divided into maternal obesity group and normal control group and fed with normal diet until 8 weeks after weaning. From each group of mice， 8 male offspring were randomly selected and executed after anesthesia. From them，testes and epididymis tissues were isolated，sperm quality was evaluated，testicular sex hormone levels were detected by ELISA，testes were analyzed using by immunofluorescence Expression levels of mRNA and protein for FOXO1 and Nrf2 genes were detected by qPCR and Western blot，respectively. RESULTS： Compared with the control group，sperm concentrations，sperm motilities and forward motion sperm ratios were significantly lower (P<0.01) and the sperm malformation rates were significantly higher (P<0.01) in the maternal obese mice. Other test results showed that maternal obesity could cause testicular tissue damage in the offspring， disturbance in testicular endocrine hormone secretion， elevated testicular tissue ROS levels， significantly increased expression levels of the spermatogonial marker FOXO1， and elevated oxidative stress levels and Nrf2 protein expressions (all P<0.01). CONCLUSION： Due to maternal obesity， oxidative stress levels were elevated in testicular tissues of offspring male mice which might have caused impaired their spermatogonial differentiation and reproductive capacity.

Key words: maternal obesity, male offspring, spermatogonia, spermatogenesis, FOXO1

CLC Number:

R589.2

YIN Rui, YUE Xiaofeng, TAN Xiaoyin, LI Lianbing, LU Daru. Effects of obese female mice on fertility of male offspring and its mechanism[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(2): 109-115.

References

[1] WANG L M, ZHOU B, ZHAO Z P, et al. Body-mass index and obesity in urban and rural China: findings from consecutive nationally representative surveys during 2004-2018[J]. Lancet, 2021, 398(10294): 53-63.
[2] WANG M C, FREANEY P M, PERAK A M, et al. Trends in prepregnancy obesity and association with adverse pregnancy outcomes in the United States, 2013 to 2018[J]. J Am Heart Assoc, 2021, 10(17): e020717.
[3] DRISCOLL A K, GREGORY E C W. Increases in prepregnancy obesity: United States, 2016-2019[J]. NCHS Data Brief, 2020(392): 1-8.
[4] MOUTON A J, LI X, HALL M E, et al. Obesity, hypertension, and cardiac dysfunction: novel roles of immunometabolism in macrophage activation and inflammation[J]. Circ Res, 2020, 126(6): 789-806.
[5] PAVLOV V A. The evolving obesity challenge: targeting the vagus nerve and the inflammatory reflex in the response[J]. Pharmacol Ther, 2021, 222: 107794.
[6] PICHÉ M E, TCHERNOF A, DESPRÉS J P. Obesity phenotypes, diabetes, and cardiovascular diseases[J]. Circ Res, 2020, 126(11): 1477-1500.
[7] OLIVEIRA P F, SOUSA M, SILVA B M, et al. Obesity, energy balance and spermatogenesis[J]. Reproduction, 2017, 153(6): R173-R185.
[8] BAUTISTA C J, RODRÍGUEZ-GONZÁLEZ G L, MORALES A, et al. Maternal obesity in the rat impairs male offspring aging of the testicular antioxidant defence system[J]. Reprod Fertil Dev, 2017, 29(10): 1950-1957.
[9] MAO J D, PENNINGTON K A, TALTON O O, et al. In utero and postnatal exposure to high fat, high sucrose diet suppressed testis apoptosis and reduced sperm count[J]. Sci Rep, 2018, 8(1): 7622.
[10] RODRÍGUEZ-GONZÁLEZ G L, VEGA C C, BOECK L, et al. Maternal obesity and overnutrition increase oxidative stress in male rat offspring reproductive system and decrease fertility[J]. Int J Obes (Lond), 2015, 39(4): 549-556.
[11] GE Z J, LIANG Q X, HOU Y, et al. Maternal obesity and diabetes may cause DNA methylation alteration in the spermatozoa of offspring in mice[J]. Reprod Biol Endocrinol, 2014, 12: 29.
[12] SARKER G, SUN W F, ROSENKRANZ D, et al. Maternal overnutrition programs hedonic and metabolic phenotypes across generations through sperm tsRNAs[J]. Proc Natl Acad Sci U S A, 2019, 116(21): 10547-10556.
[13] LIU Y X, LIN C, LUO X X, et al. Research progress on the relationship between obesity-inflammation-aromatase axis and male infertility[J]. Oxid Med Cell Longev, 2021, 2021: 6612796.
[14] GODFREY K M, REYNOLDS R M, PRESCOTT S L, et al. Influence of maternal obesity on the long-term health of offspring[J]. Lancet Diabetes Endocrinol, 2017, 5(1): 53-64.
[15] SANTOS M, RODRÍGUEZ-GONZÁLEZ G L, IBÁÑEZ C, et al. Adult exercise effects on oxidative stress and reproductive programming in male offspring of obese rats[J]. Am J Physiol Regul Integr Comp Physiol, 2015, 308(3): R219-R225.
[16] FERLIN A, GAROLLA A, GHEZZI M, et al. Sperm count and hypogonadism as markers of general male health[J]. Eur Urol Focus, 2021, 7(1): 205-213.
[17] TAN K, WILKINSON M F. A single-cell view of spermatogonial stem cells[J]. Curr Opin Cell Biol, 2020, 67: 71-78.
[18] HERMANN B P, CHENG K R, SINGH A, et al. The mammalian spermatogenesis single-cell transcriptome, from spermatogonial stem cells to spermatids[J]. Cell Rep, 2018, 25(6): 1650-1667.e8.
[19] YOUNGSON N A, UDDIN G M, DAS A, et al. Impacts of obesity, maternal obesity and nicotinamide mononucleotide supplementation on sperm quality in mice[J]. Reproduction, 2019, 158(2): 169-179.
[20] SU Y F, HE L T, HU Z Y, et al. Obesity causes abrupt changes in the testicular microbiota and sperm motility of zebrafish[J]. Front Immunol, 2021, 12: 639239.
[21] MENEGHINI M A, GALARZA R A, FLORES QUIROGA J P, et al. Diet-induced maternal obesity and overnutrition cause a decrease in the sperm quality of the offspring[J]. J Nutr Biochem, 2022, 103: 108966.
[22] GOERTZ M J, WU Z R, GALLARDO T D, et al. Foxo1 is required in mouse spermatogonial stem cells for their maintenance and the initiation of spermatogenesis[J]. J Clin Invest, 2011, 121(9): 3456-3466.
[23] WANG J S, BAO B H, FENG J L, et al. Effects of diabetes mellitus on sperm quality in the Db/Db mouse model and the role of the FoxO1 pathway[J]. Med Sci Monit, 2021, 27: e928232.
[24] LIU T T, CHEN X X, LI T J, et al. Histone methyltransferase SETDB1 maintains survival of mouse spermatogonial stem/ progenitor cells via PTEN/AKT/FOXO1 pathway[J]. Biochim Biophys Acta Gene Regul Mech, 2017, 1860(10): 1094-1102.
[25] TAKESHIMA T, USUI K, MORI K, et al. Oxidative stress and male infertility[J]. Reprod Med Biol, 2020, 20(1): 41-52.
[26] ZHAO X S, GAN L X, PAN H Y, et al. Multiple elements regulate nuclear/cytoplasmic shuttling of FOXO1: characterization of phosphorylation-and 14-3-3-dependent and-independent mechanisms[J]. Biochem J, 2004, 378(Pt 3): 839-849.
[27] MITTLER R, VANDERAUWERA S, SUZUKI N, et al. ROS signaling: the new wave?[J]. Trends Plant Sci, 2011, 16(6): 300-309.
[28] KOPS G J, DANSEN T B, POLDERMAN P E, et al. Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress[J]. Nature, 2002, 419(6904): 316-321.
[29] LIN C C, YANG C C, HSIAO L D, et al. Carbon monoxide releasing molecule-3 enhances heme oxygenase-1 induction via ROS-dependent FoxO1 and Nrf2 in brain astrocytes[J]. Oxid Med Cell Longev, 2021, 2021: 5521196.

Effects of obese female mice on fertility of male offspring and its mechanism

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