Metabolic Control of Reproduction

A minimum amount of stored energy is required to maintain fertility. When survival is threatened by scarcity of food or increased energy demands, male and female of most species divert energy away from reproduction. This includes sexual maturation, the production of reproductive hormones and gametes, and the maintenance of pregnancy and lactation. If excessive leanness occurs in young women, puberty is often delayed. On the other hand, excess energy also negatively impacts fertility. Obesity aggravates polycystic ovary syndrome, ovulatory dysfunctions and may induce hypothalamic hypogonadism. In males, increased adiposity may cause defective gonadal steroidogenesis, decreased sperm quality and subfertility. Our studies aim to unravel the neural circuitry and the molecular pathways linking metabolic cues (e.g., leptin, insulin) and reproductive function.

Hill and Elias, Physiol Reviews 2018

Mouse Models for Translational Studies in Reproductive Sciences

Infertility in humans may be caused by monogenic loss-of-function mutations. In collaboration with laboratories specialized in human genetics, we develop novel mouse models to allow functional studies and experimentation. For example, we described recently that homozygous mutation of POLR3H/Polr3h gene in humans and mice cause primary ovarian insufficiency. We have generated the Kiss1-Cre, the Kiss1-hrGFP and the ProkR2-Cre mouse models. Loss-of-function mutation in KISS1/Kiss1 and PROKR2/Prokr2 genes cause infertility in humans and mice. We use the Cre-loxP system and viral vectors to determine the neural circuitry and molecular pathways associated with the role of those genes in reproductive function.

Cravo et al., 2013

Mohsen et al., 2017

Transcriptome Analysis of Hypothalamic Neurons

The hypothalamic ventral premammillary nucleus (PMv) is a key site of leptin action in pubertal development and reproduction. Our lab showed that endogenous re-expression of leptin receptor (LepR) only in PMv neurons is sufficient for pubertal development and improvement of fertility of otherwise infertile LepR null mice. Recent studies have suggested that the arcuate nucleus (Arc) also plays a role. We use RNA-seq and TRAP-seq to unravel new candidate genes in the PMV and Arc associated with leptin action in the neuroendocrine reproductive axis.