Leptin restores markers of female fertility in lipodystrophy

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1864

Article

Eifler, Lisa^1,2  Hoffmann, Annett¹  Wagner, Isabel Viola^2,3,4  Kloeting, Nora⁵  Sahlin, Lena^3,4  Ebert, Thomas^1,5  Jessnitzer, Beate¹  Loessner, Ulrike¹  Stumvoll, Michael¹  Soder, Olle^3,4  Fasshauer, Mathias^1,5,6  Kralisch, Susan⁵ 

[1] Univ Leipzig, Dept Endocrinol & Nephrol, D-04103 Leipzig, Germany

[2] Univ Cologne, Dept Pediat, Cologne, Germany

[3] Karolinska Inst, S-17176 Stockholm, Sweden

[4] Univ Hosp, Dept Womens & Childrens Hlth, Pediat Endocrinol Unit, S-17176 Stockholm, Sweden

[5] Univ Leipzig, Med Ctr, IFB AdiposityDis, D-04103 Leipzig, Germany

[6] Justus Liebig Univ, Inst Nutr Sci, Goethestr 55, D-35390 Giessen, Germany

关键词: Fertility;    Leptin;    Lipodystrophy;    Reproduction;   

DOI  :  10.1016/j.bbadis.2018.07.015

来源: Elsevier

【 摘 要 】

Objectives: Female reproductive dysfunction occurs in patients with pathological loss of adipose tissue, i.e. lipodystrophy (LD). However, mechanisms remain largely unclear and treatment effects of adipocyte-derived leptin have not been assessed in LD animals. Methods: In the current study, C57131/6 LD mice on a low-density lipoprotein receptor knockout background were treated with leptin or saline for 8 weeks and compared to non-LD controls. Results: The number of pups born was 37% lower in breeding pairs consisting of LD female mice x non-LD male mice (n = 3.3) compared to LD male mice x non-LD female mice (n = 5.2) (p < 0.05). Mean uterus weight was significantly lower in the saline-treated LD group (18.8 mg) compared to non-LD controls (52.9 mg; p < 0.0001) and increased significantly upon leptin treatment (46.5 mg; p < 0.001). The mean number of corpora lutea per ovary was significantly lower in saline-treated LD animals compared to non-LD controls (p < 0.01) and was restored to non-LD control levels by leptin (p < 0.05). Mechanistically, mRNA expression of ovarian follicle stimulating hormone receptor (p < 0.01) and estrogen receptor beta (p < 0.05), as well as of pituitary luteinizing hormone beta subunit (p < 0.001) and follicle-stimulating hormone beta subunit (p < 0.05), was significantly up regulated in LD mice compared to non-LD controls. In addition, mean time to vaginal opening as a marker of puberty onset was delayed by 12.5 days in LD mice (50.9 days) compared to non-LD controls (38.4 days; p < 0.001). Conclusions: Female LD animals show impaired fertility which is restored by leptin. Future studies should assess leptin as a subfertility treatment in human leptin-deficiency disorders.

【 授权许可】

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