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

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.