| First Author | Eifler L | Year | 2018 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1864 |
| Issue | 10 | Pages | 3292-3297 |
| PubMed ID | 30021121 | Mgi Jnum | J:273797 |
| Mgi Id | MGI:6277187 | Doi | 10.1016/j.bbadis.2018.07.015 |
| Citation | Eifler L, et al. (2018) Leptin restores markers of female fertility in lipodystrophy. Biochim Biophys Acta Mol Basis Dis 1864(10):3292-3297 |
| abstractText | 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, C57Bl/6 LD mice on a low-density lipoprotein receptor knockout background were treated with leptin or saline for 8weeks 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 (18.8mg) compared to non-LD controls (52.9mg; p<0.0001) and increased significantly upon leptin treatment (46.5mg; 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 upregulated in LD mice compared to non-LD controls. In addition, mean time to vaginal opening as a marker of puberty onset was delayed by 12.5days in LD mice (50.9days) compared to non-LD controls (38.4days; 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. |
