How the quest to improve sheep reproduction provided insight into oocyte control of follicular development

Reproductive efficiency is a key driver of profitability in sheep meat production. Thus developing new strategies to increase reproductive efficiency has been a focus of many researchers. However, what we learn from understanding processes controlling reproductive efficiency in sheep also provides insights into fundamental mechanisms controlling reproduction in mammals, including humans. A prime example is the discovery that inactivating mutations in the related oocyte-derived growth factors, bone morphogenetic protein 15 and growth differentiation factor 9, result in an unusual phenotype in sheep. Animals heterozygous for inactivating mutations in either of these genes have increased fertility whereas those that are homozygous are sterile. Understanding how this phenotype was generated led to a paradigm shift in our thinking, highlighting the central role of the oocyte in controlling ovarian follicular development and ovulation rate. It also highlighted the need for comparative research models across multiple species to truly understand these important mechanisms.