La administración de tungstato sódico restaura la ovulación y la fertilidad en ratones infértiles IRS2−/−

Abstract

Insulin receptor substrate-2 (IRS-2) gene suppression induces an alteration of hypothalamic-ovarian axis as a result of central leptin resistance induction. IRS-2^−/−females mice are characterised by persistent anovulation, accompanied by the absence of the oestrous cycle, which results in a marked reduction in fertility (pregnancy rate: 9% IRS-2^−/− vs. 100% IRS-2^wt). Sodium tungstate (Na₂WO₄) has demonstrated its ability to reverse the leptin resistance state through an inhibition of phosphatases involved in the signalling pathway of several cytokines. The objective of this work is to present an experimental approach to determine a potential interest towards Na₂WO₄ in the reproductive ability of anovulatory IRS-2^−/− female mice.

Material and methods

Na₂WO₄ was administered in drinking water (2 g/L) to female mice. The oestrous cycle was assessed through vaginal smears, and pregnancy rates were measured after mating with IRS-2^wt males.

Results

Lack of oestrous cycle was confirmed in the mice during the pre-treatment period. After 7 days of treatment all animals showed delayed cycle phases (oestrous and meta-oestrous) in vaginal smears, indicating a recovery of normal ovulatory cycle. At the end of the study, after mating with competent IRS-2^wt male, 80% of females treated with Na₂WO₄ were pregnant. These results show a fertility recovery, as opposed to the pregnancy rate described in untreated IRS-2^−/− (9%).

Conclusions

For the first time, a description is presented of the direct effect of Na₂WO₄ in the restoration of ovarian function and fertility in IRS-2^−/− female mice.