Exit from M-phase requires a precise sequence of molecular events for successful completion, with errors in the process resulting in cell death or aneuploidy, a characteristic feature of cancer and the leading cause of pregnancy failure. Exit from the second meiotic division (MII) in oocytes is a unique event triggered by sperm, involving female anaphase II as well as both male and female pronuclear formation. Very little is known about how these events involving two distinct cell types are coordinated.
View Article and Find Full Text PDFChemotherapy induced ovarian failure and infertility is an important concern in female cancer patients of reproductive age or younger, and non-invasive, pharmacological approaches to maintain ovarian function are urgently needed. Given the role of reduced nicotinamide adenine dinucleotide phosphate (NADPH) as an essential cofactor for drug detoxification, we sought to test whether boosting the NAD(P) metabolome could protect ovarian function. We show that pharmacological or transgenic strategies to replenish the NAD metabolome ameliorates chemotherapy induced female infertility in mice, as measured by oocyte yield, follicle health, and functional breeding trials.
View Article and Find Full Text PDFFemales are born with a finite and non-renewable reservoir of oocytes, which therefore decline both in number and quality with advancing age. A striking characteristic of oocyte quality is that "ageing" effects manifest whilst women are in their thirties and are therefore still chronologically and physically young. Furthermore, this decline is unrelenting and not modifiable to any great extent by lifestyle or diet.
View Article and Find Full Text PDFEmbryonic genome activation (EGA) marks the transition from dependence on maternal transcripts to an embryonic transcriptional program. The precise temporal regulation of gene expression, specifically the silencing of the Dux/murine endogenous retrovirus type L (MERVL) program during late 2-cell interphase, is crucial for developmental progression in mouse embryos. How this finely tuned regulation is achieved within this specific window is poorly understood.
View Article and Find Full Text PDFObjective: To study the fertility treatment pathways used by women with and without polycystic ovary syndrome (PCOS) and which pathways were more likely to result in a birth.
Design: This retrospective national community-based cohort study used longitudinal self-report survey data (collected 1996-2022; aged 18-49 years) from women born in 1973-1978 who are participants in the Australian Longitudinal Study on Women's Health. The study also used linked administrative data on fertility treatments (1996-2021).