Journal article

Publication year: 2018

Pages: 3292-3297

Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Volume number: 1864

Issue number: 10

ISSN: 0925-4439

Open access status: Green

DOI Link: https://doi.org/10.1016/j.bbadis.2018.07.015

Publisher: Elsevier

Abstract: 
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.

Harvard Citation style: Eifler, L., Hoffmann, A., Wagner, I., Klöting, N., Sahlin, L., Ebert, T., et al. (2018) Leptin restores markers of female fertility in lipodystrophy, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1864(10), pp. 3292-3297. https://doi.org/10.1016/j.bbadis.2018.07.015

APA Citation style: Eifler, L., Hoffmann, A., Wagner, I., Klöting, N., Sahlin, L., Ebert, T., Jessnitzer, B., Lössner, U., Stumvoll, M., Söder, O., Fasshauer, M., & Kralisch, S. (2018). Leptin restores markers of female fertility in lipodystrophy. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1864(10), 3292-3297. https://doi.org/10.1016/j.bbadis.2018.07.015