# What we could not have known: ovarian cycles, follicle development, and the signature of life

## TL;DR

The paper explores reproductive cycles, follicle development, and the role of zinc as a signaling element in ovarian function.

## Contribution

The discovery of the 'zinc spark' as the first external signal of a new organism and the molecular basis of inhibin's negative feedback in the ovary.

## Key findings

- Zinc acts as a signaling element in ovarian cycles, comparable to phosphate and calcium.
- The zinc spark is identified as the first external signal of a new organism.
- Ex vivo environments were engineered to support ovarian follicle development.

## Abstract

Reproductive science is a discipline of generation and for generations. Our work has focused on the signals that drive reproductive cycles at the organismal and the organ level. The principal endocrine signals of male and female reproductive cycles include inhibin and activin, traditional peptide hormones, and at the cellular level, zinc, a workhorse element now elevated to the role of a signal on par with phosphate and calcium. Our studies relied on and built technologies to make our discoveries, including enzymatic sequencing and PCR, alginate beads and microfluidics, and sophisticated elemental imaging and quantitation. Taken together, we described the molecular basis of negative feedback by inhibin in the ovary, engineered ex vivo environments for ovarian follicle development, and discovered the first external signal of a new organism, the zinc spark. Some of this work is being applied to patients who are in danger of losing their fertility in a variety of settings, including during cancer care, a medical field called oncofertility. Advances in reproductive science beckon us to see ourselves in the future, and with the discoveries described here, our view extends further.

My career began in 1985 with admission to graduate school at Northwestern University, followed by a postdoc at Genentech and a faculty position at Northwestern University in 1995. Along the way, we made key discoveries and created centers that benefited the field.

My career began in 1985 with admission to graduate school at Northwestern University, followed by a postdoc at Genentech and a faculty position at Northwestern University in 1995. Along the way, we made key discoveries and created centers that benefited the field.