Perinatal determinants of female fertility and reproductive longevity

In the McKey Lab, we are applying a multiscale approach encompassing protein and RNA localization in 3D, single-cell transcriptomics, long-term fertility studies, and genetic models to investigate how tissue interactions during development modulate adult phenotypes, using the mouse ovary as a model.

The question that most animates the field of mammalian ovary biology surrounds the biological basis for finite female reproductive longevity: why are so many oocytes lost throughout life, and how are they selected for fertility?

During fetal development, the differentiation of ovarian cells culminates in the assembly of two distinct populations of ovarian follicles: medullary follicles and cortical follicles. 

Medullary follicles assemble in the middle of the ovary and undergo activation almost immediately after birth. However, these do not contribute to female fertility past the first litter. 

Cortical follicles, which assemble in the surface of the ovary, remain quiescent until puberty and constitute the ovarian reserve. Sequential activation of cortical follicles at each cycle produces ovulated eggs during the entire reproductive lifespan of the adult female.

Because this reserve is never replenished, differences in the establishment of cortical and medullary regions during perinatal life have permanent effects on the ovarian reserve and reproductive potential of the adult female. 

The mechanisms that lead to the allocation of granulosa and oocytes into medullary or cortical compartment are still not known. 

The goal of our research is to decipher the structural mechanisms that drive ovary regionalization and cellular differentiation in perinatal life, and how modulation of these mechanisms alters adult ovarian functions and female reproductive longevity.

We are approaching this long-term goal from three perspectives:

1) Relationship between morphogenesis and establishment of function