The number of primordial follicles in the ovarian reserve is an important determinant of the length of the ovarian lifespan and therefore the fertility of an individual. This reserve contains all the oocytes potentially available for fertilisation throughout the fertile lifespan. The maximum number is set during pregnancy or just after birth in most mammalian species; current evidence does not support neofolliculogenesis after the ovarian reserve is established, although this is increasingly being re-examined. Under physiological circumstances, this number will be influenced by the number of primordial germ cells (PGCs) initially specified in the epiblast of the developing embryo, their proliferation during and after migration to the developing gonads, and their death during oogenesis and formation of primordial follicles at nest breakdown. Death of germ cells during the establishment of the ovarian reserve occurs principally by autophagy or apoptosis, although the triggers that initiate these remain elusive. This review outlines the regulatory steps that determine the number of primordial follicles and thus of oocytes in the ovarian reserve at birth, using the mouse as the model interspersed with human data where available. This information has application for understanding the variability in duration of fertility in that occurs between normal individuals and with age, in premature ovarian insufficiency, and after chemo- or radiotherapy.

Approximately seventy percent of ovarian cancer patients succumb to the disease within the first 5 years of diagnosis, even after successful surgery and effective chemotherapy treatment. A small subset of chemotherapy resistant cancer stem cells (CSCs) cause relapse of ovarian cancers. This study investigated the association between paclitaxel-mediated Src activation (p-Src) and CSC populations in driving ovarian cancer progression. We demonstrate that patients with high-stage serous ovarian carcinomas have significantly elevated levels of p-Src, compared to patient with low-stage and benign ovarian tumours. Additionally, p-Src was significantly enhanced in ascites-derived tumour cells obtained from recurrent patients, compared to chemonaïve patients. Paclitaxel treatment increased Src activation in ovarian cancer cells, causing enrichment of CSC marker expression in the surviving cells in vitro and in xenografts of nude mice. Dasatinib in combination with paclitaxel significantly suppressed p-Src in ovarian cancer cell lines and xenografts but had no effect on the expression of CSC markers. However, combination of paclitaxel and Dasatinib showed lower trend in invasion in liver and pancreas, compared to paclitaxel-only treatment. The tumours treated with combination therapy also had significantly lower infiltration of mononuclear cells. Robust recurrent tumour growth was observed in all mice groups after termination of treatments. The above results suggest that Dasatinib-mediated inhibition of p-Src may not be crucial for paclitaxel-induced CSC-mediated recurrence in ovarian cancer.

Approximately sixty per cent of ovarian cancer patients die within the first five years of diagnosis due to recurrence associated with chemoresistance. The metzincin family of metalloproteinases is enzymes involved in matrix remodeling in response to normal physiological changes and diseased states. Recently, there has been a mounting awareness of these proteinases and their endogenous inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), as superb modulators of cellular communication and signaling regulating key biological processes in cancer progression. This review investigates the role of metzincins and their inhibitors in ovarian cancer. We propose that understanding the metzincins and TIMP biology in ovarian cancer may provide valuable insights in combating ovarian cancer progression and chemoresistance-mediated recurrence in patients.

Reproductive sciences have made major contributions to human health, livestock production and environmental management in the past and will continue to do so in future. In collaboration with other disciplines, reproductive scientists can provide scientifically valid information that will allow the rational development of policies on topics such as declining fertility in men and women, livestock breeding efficiencies, climate change, pest animal control, wildlife management and environmental influences. It is imperative that the reproductive sciences are recognised by the community and policy makers as important contributors to future health and welfare of animals, humans and the planet if these potential benefits are to be captured and utilised. Reproductive Health Australia (RHA) was launched recently to advocate for reproductive biology as a national health, economic and social priority. This short review provides a snapshot of why it is imperative that reproductive science receives the recognition that is due to it and provides examples of how it can contribute to the future of the planet.