Effects of Exogenous Adiponectin Supplementation in Early Pregnant PCOS Mice on the Metabolic Syndrome of Adult Female Offspring

Overview

Journal J Ovarian Res

Publisher Biomed Central

Specialties Gynecology & Obstetrics
Reproductive Medicine

Date 2021 Jan 18

PMID 33455575

Citations 8

Authors

Meng Zuo

Guotao Liao

Wenqian Zhang

Dan Xu

Juan Lu

Manhong Tang

Yue Yan

Chenghao Hong

Yuxia Wang

Affiliations

Soon will be listed here.

Abstract

Objective: PCOS is a heterogeneous endocrine disorder with both reproductive and metabolic abnormalities. At present, PCOS has been confirmed to have a certain genetic background. Compared with healthy women, the vast majority of PCOS patients have hyperandrogenemia, and this excessive androgen exposure during pregnancy may affect the development of female fetuses. The aim of the current study was to investigate the effect of adiponectin intervention during early pregnancy of obese mice with PCOS on the metabolic phenotype of adult female offspring.

Methods: After the PCOS model was established, C57BL/6J mice were divided into maternal-control, maternal-PCOS, and maternal-PCOS + APN groups. DHEA-induced PCOS mice were supplemented with adiponectin (10 mg/kg/day) in the early pregnancy in order to eliminate adverse hormone exposure and then traced for endocrine indicators in their adult female offspring, which were observed for metabolism syndrome or endocrine disturbance and exhibited the main effects of APN. To further explore the underlying mechanism, the relative expressions of phosphorylated AMPK, PI3K, and Akt were detected in the ovaries of offspring mice.

Results: The serum testosterone level of the maternal-PCOS + APN group in early pregnancy was significantly lower than that of the maternal-PCOS group (p < 0.01). The serum testosterone level in the offspring-PCOS + APN group was significantly lower than in the offspring-PCOS group (p <0.05), the diestrus time characterized by massive granulocyte aggregation in the estrus cycle was significantly shorter than in the offspring-PCOS group (p<0.05), and the phenotypes of PCOS-like reproductive disorders and metabolic disorders, such as obesity, insulin resistance, impaired glucose tolerance, and hyperlipidemia, were also significantly improved in the offspring-PCOS + APN group (p < 0.05). Compared with the control group, the expression levels of phosphorylated AMPK, PI3K, and Akt in the offspring-PCOS group were significantly decreased (p < 0.05), while those in the offspring-PCOS + APN group were significantly increased (p < 0.05).

Conclusions: APN intervention in early pregnancy significantly reduced the adverse effects of maternal obesity and high androgen levels during pregnancy on female offspring and corrected the PCOS-like endocrine phenotype and metabolic disorders of adult female offspring. This effect may be caused by the activation of the AMPK/PI3K-Akt signaling pathway in PCOS offspring mice.

Citing Articles

Metformin-mediated intestinal AMPK activation ameliorates PCOS through gut microbiota modulation and metabolic pathways.

Xu Y, Ning L, Si Y, Li X, Wang R, Ren Q Front Endocrinol (Lausanne). 2025; 16:1526109.

PMID: 40041289 PMC: 11876036. DOI: 10.3389/fendo.2025.1526109.

Serum adiponectin level is negatively related to insulin resistance in women with polycystic ovary syndrome.

Yang J, Lin M, Tian X, Li C, Wu H, Deng L Endocr Connect. 2024; 14(1).

PMID: 39475750 PMC: 11728917. DOI: 10.1530/EC-24-0401.

Usefulness of the Sympto-Thermal Method with Standardized Cervical Mucus Assessment (InVivo Method) for Evaluating the Monthly Cycle in Women with Polycystic Ovary Syndrome (PCOS).

Stachowska A, Kicinska A, Kotulak-Chrzaszcz A, Babinska A Healthcare (Basel). 2024; 12(11).

PMID: 38891183 PMC: 11172004. DOI: 10.3390/healthcare12111108.

Effect of nanocurcumin on fertility in murine model of polycystic ovary syndrome.

Aaly-Gharibeh Z, Hosseinchi M, Shalizar-Jalali A Vet Res Forum. 2024; 15(2):113-117.

PMID: 38465321 PMC: 10924291. DOI: 10.30466/vrf.2023.2006604.3935.

Minipuberty in Sons of Women with Low Vitamin D Status during Pregnancy.

Kowalcze K, Krysiak R, Obuchowicz A Nutrients. 2023; 15(22).

PMID: 38004122 PMC: 10674928. DOI: 10.3390/nu15224729.

References

Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T, Iwabu M . Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med. 2007; 13(3):332-9. DOI: 10.1038/nm1557. View

Escobar-Morreale H . Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol. 2018; 14(5):270-284. DOI: 10.1038/nrendo.2018.24. View

Kuscu N, Var A . Oxidative stress but not endothelial dysfunction exists in non-obese, young group of patients with polycystic ovary syndrome. Acta Obstet Gynecol Scand. 2009; 88(5):612-7. DOI: 10.1080/00016340902859315. View

Spranger J, Kroke A, Mohlig M, Bergmann M, Ristow M, Boeing H . Adiponectin and protection against type 2 diabetes mellitus. Lancet. 2003; 361(9353):226-8. DOI: 10.1016/S0140-6736(03)12255-6. View

Wild R, Carmina E, Diamanti-Kandarakis E, Dokras A, Escobar-Morreale H, Futterweit W . Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society. J Clin Endocrinol Metab. 2010; 95(5):2038-49. DOI: 10.1210/jc.2009-2724. View

McAllister J, Legro R, Modi B, Strauss 3rd J . Functional genomics of PCOS: from GWAS to molecular mechanisms. Trends Endocrinol Metab. 2015; 26(3):118-24. PMC: 4346470. DOI: 10.1016/j.tem.2014.12.004. View

Chopra I, Li H, Wang H, Webster K . Phosphorylation of the insulin receptor by AMP-activated protein kinase (AMPK) promotes ligand-independent activation of the insulin signalling pathway in rodent muscle. Diabetologia. 2011; 55(3):783-94. PMC: 4648248. DOI: 10.1007/s00125-011-2407-y. View

Caldwell A, Eid S, Kay C, Jimenez M, McMahon A, Desai R . Haplosufficient genomic androgen receptor signaling is adequate to protect female mice from induction of polycystic ovary syndrome features by prenatal hyperandrogenization. Endocrinology. 2015; 156(4):1441-52. DOI: 10.1210/en.2014-1887. View

Melo A, Dias S, de Carvalho Cavalli R, Cardoso V, Bettiol H, Barbieri M . Pathogenesis of polycystic ovary syndrome: multifactorial assessment from the foetal stage to menopause. Reproduction. 2015; 150(1):R11-24. DOI: 10.1530/REP-14-0499. View

10.

Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S . Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med. 2002; 8(11):1288-95. DOI: 10.1038/nm788. View

11.

Roland A, Moenter S . Prenatal androgenization of female mice programs an increase in firing activity of gonadotropin-releasing hormone (GnRH) neurons that is reversed by metformin treatment in adulthood. Endocrinology. 2010; 152(2):618-28. PMC: 3037157. DOI: 10.1210/en.2010-0823. View

12.

Teede H, Misso M, Costello M, Dokras A, Laven J, Moran L . Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril. 2018; 110(3):364-379. PMC: 6939856. DOI: 10.1016/j.fertnstert.2018.05.004. View

13.

Yan X, Yuan C, Zhao N, Cui Y, Liu J . Prenatal androgen excess enhances stimulation of the GNRH pulse in pubertal female rats. J Endocrinol. 2014; 222(1):73-85. DOI: 10.1530/JOE-14-0021. View

14.

Norman R, Dewailly D, Legro R, Hickey T . Polycystic ovary syndrome. Lancet. 2007; 370(9588):685-97. DOI: 10.1016/S0140-6736(07)61345-2. View

15.

Sir-Petermann T, Maliqueo M, Codner E, Echiburu B, Crisosto N, Perez V . Early metabolic derangements in daughters of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2007; 92(12):4637-42. DOI: 10.1210/jc.2007-1036. View

16.

Qiao L, Wattez J, Lee S, Nguyen A, Schaack J, Hay Jr W . Adiponectin Deficiency Impairs Maternal Metabolic Adaptation to Pregnancy in Mice. Diabetes. 2017; 66(5):1126-1135. PMC: 5399613. DOI: 10.2337/db16-1096. View

17.

Dumesic D, Lobo R . Cancer risk and PCOS. Steroids. 2013; 78(8):782-5. DOI: 10.1016/j.steroids.2013.04.004. View

18.

Xenopoulos P, Kang M, Puliafito A, Di Talia S, Hadjantonakis A . Heterogeneities in Nanog Expression Drive Stable Commitment to Pluripotency in the Mouse Blastocyst. Cell Rep. 2015; 10(9):1508-1520. PMC: 4560681. DOI: 10.1016/j.celrep.2015.02.010. View

19.

De Leo V, Musacchio M, Cappelli V, Massaro M, Morgante G, Petraglia F . Genetic, hormonal and metabolic aspects of PCOS: an update. Reprod Biol Endocrinol. 2016; 14(1):38. PMC: 4947298. DOI: 10.1186/s12958-016-0173-x. View

20.

Horike N, Sakoda H, Kushiyama A, Ono H, Fujishiro M, Kamata H . AMP-activated protein kinase activation increases phosphorylation of glycogen synthase kinase 3beta and thereby reduces cAMP-responsive element transcriptional activity and phosphoenolpyruvate carboxykinase C gene expression in the liver. J Biol Chem. 2008; 283(49):33902-10. PMC: 2662216. DOI: 10.1074/jbc.M802537200. View