# Central SELENOT deficiency impairs gonadotrope axis function, sexual behavior, and fertility in male and female mice

## TL;DR

This study shows that a selenoprotein called SELENOT is essential for brain-controlled reproduction, as its deficiency causes fertility issues and sexual behavior problems in mice.

## Contribution

The study reveals SELENOT's novel role in regulating the gonadotrope axis and reproductive function through redox control of GnRH neurons.

## Key findings

- SELENOT deficiency in the brain impairs sexual behavior and fertility in both male and female mice.
- SELENOT deficiency causes elevated GnRH and LH levels, and a polycystic ovary-like phenotype in females.
- LH pulse secretion is disrupted in SELENOT-deficient mice, and this can be reversed with a GnRH antagonist.

## Abstract

Reproductive disorders can result from a defective action of the neuropeptide gonadotropin-releasing hormone (GnRH), the master regulator of reproduction. We have previously shown that selenoprotein T (SELENOT), a newly described thioredoxin-like selenoprotein highly expressed in endocrine and neuroendocrine cells, plays a role in hormone secretion and neuroprotection. However, whether SELENOT is involved in neuroendocrine regulation in vivo is totally unknown. We found that SELENOT deficiency in the brain impaired sexual behavior, leading to a decline in fertility in both male and female mice. Biochemical and histological analyses of the gonadotrope axis of these mice revealed a higher expression of GnRH, which is associated with circulating luteinizing hormone (LH) excess, and elevated steroid hormones in males and a polycystic ovary syndrome–like phenotype in females. In addition, SELENOT deficiency impaired LH pulse secretion in both male and female mice. These changes were reverted after administration of a GnRH antagonist. Together, our data demonstrate for the first time to our knowledge the role of a selenoprotein in the central control of sexual behavior and reproduction, and identify a redox effector of GnRH neuron activity impacting both male and female reproductive function.

Selenoproteins constitute a powerful antioxidant arsenal in mammals. Here, we found that disruption of SELENOT in the brain, a selenoprotein involved in the protection against cellular stress, leads to impairement of sexual behavior and a significant decline in fertility, indicating that selenium and selenoprotein are essential for the control of reproduction by the brain.