Quantitative analysis of tissues and organs can reveal large-scale patterning as well as the impact of perturbations and aging on biological architecture. Here we develop tools for imaging of single cells in intact organs and computational approaches to assess spatial relationships in 3D. In the mouse ovary, we use nuclear volume of the oocyte to read out quiescence or growth of oocyte-somatic cell units known as follicles. This in-ovary quantification of non-growing follicle dynamics from neonate to adult fits a mathematical function, which corroborates the model of fixed oocyte reserve. Mapping approaches show that radial organization of folliculogenesis established in the newborn ovary is preserved through adulthood. By contrast, inter-follicle clustering increases during aging with different dynamics depending on size. These broadly applicable tools can reveal high dimensional phenotypes and age-related architectural changes in other organs. In the adult mouse pancreas, we find stochastic radial organization of the islets of Langerhans but evidence for localized interactions among the smallest islets.

Premature ovarian failure (POF) is defined as cessation of menstruation and associated elevation of gonadotropin levels (FSH >40 IU/l) as a result of decreased ovarian function prior to the age of 40. An estimated 1% of the population is affected before age 40, with 0.1% affected prior to age 30. Although the causes for POF are many, the majority of POF cases have idiopathic etiologies. In an effort to investigate potential mechanisms of the disease, genetic determinants of POF have received particular attention in recent years. Transgenic mouse models have been instrumental in the discovery of novel genetic determinants of gonadal development and failure and have informed research identifying mutations in women with POF. Here, we review recent developments in identifying genetic determinants of POF.

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