Evaluating the impact of a neonatal litter size manipulation on offspring adiposity and assisted reproduction outcomes (#475)
Infertility is a significant reproductive health concern in Aotearoa New Zealand (1). Elevated body mass index (BMI) and obesity are associated with poorer fertility and assisted reproductive technology (ART) outcomes (2,3). However, BMI is an indirect measure of body composition and may not reflect metabolic health across populations (4). Neonatal litter-size manipulation provides a validated mouse model independent of dietary macronutrient manipulation and genetic modification (5). This study aims to utilise this model to determine whether increased adiposity influences follicle development, oocyte competence, and ART outcomes.
A litter size manipulation model was used to evaluate the impact of neonatal under- (12 pups/litter), control- (6 pups/litter) and over-feeding (3 pups/litter) on female offspring adiposity (5). Litter weight was monitored weekly from birth to weaning (Day 21). At weaning, one female pup per litter was weighed and euthanised. The inguinal and perigonadal fat pads were isolated and weighed, and adipose tissue weight relative to total body weight was compared between groups (N=3-6 per group). Ovaries from these animals were also collected, and follicles were cultured using an encapsulated in vitro follicle growth (eIVFG) culture system (6) to evaluate follicle survival, growth, and developmental competence. Where possible, remaining female littermates underwent superovulation and in vitro fertilisation (IVF) procedures to evaluate oocyte competency and embryo outcomes.
Preliminary results indicate that neonatal litter size manipulation altered body weight throughout the pre-weaning period, with underfed, control, and over-fed animals weighing ~8.5g, 12g and 15g at weaning. Relative inguinal and perigonadal adipose tissue weights were increased following over-feeding. Ongoing eIVFG and superovulation and IVF experiments will evaluate the impacts of altered adiposity on follicle growth and ART outcomes.
These findings validate neonatal litter-size manipulation as a model of altered adiposity and support its application for investigating the effects of adiposity on follicle development and ART outcomes.
A litter size manipulation model was used to evaluate the impact of neonatal under- (12 pups/litter), control- (6 pups/litter) and over-feeding (3 pups/litter) on female offspring adiposity (5). Litter weight was monitored weekly from birth to weaning (Day 21). At weaning, one female pup per litter was weighed and euthanised. The inguinal and perigonadal fat pads were isolated and weighed, and adipose tissue weight relative to total body weight was compared between groups (N=3-6 per group). Ovaries from these animals were also collected, and follicles were cultured using an encapsulated in vitro follicle growth (eIVFG) culture system (6) to evaluate follicle survival, growth, and developmental competence. Where possible, remaining female littermates underwent superovulation and in vitro fertilisation (IVF) procedures to evaluate oocyte competency and embryo outcomes.
Preliminary results indicate that neonatal litter size manipulation altered body weight throughout the pre-weaning period, with underfed, control, and over-fed animals weighing ~8.5g, 12g and 15g at weaning. Relative inguinal and perigonadal adipose tissue weights were increased following over-feeding. Ongoing eIVFG and superovulation and IVF experiments will evaluate the impacts of altered adiposity on follicle growth and ART outcomes.
These findings validate neonatal litter-size manipulation as a model of altered adiposity and support its application for investigating the effects of adiposity on follicle development and ART outcomes.
- Righarts, A., Dickson, N. P., Ekeroma, A., Gray, A. R., Parkin, L., & Gillett, W. R. (2021). The burden of infertility in New Zealand: A baseline survey of prevalence and service use. Australian and New Zealand Journal of Obstetrics and Gynaecology, 61(3), 439–447. https://doi.org/10.1111/ajo.13323
- Turner, F., Powell, S. G., Al-Lamee, H., Gadhvi, A., Palmer, E., Drakeley, A. J., Hapangama, D. K., & Tempest, N. (2024). Impact of body mass index on fertility in an otherwise healthy population: A systematic review and meta-analysis. BMJ Open, 14, e082123. https://doi.org/10.1136/bmjopen-2023-082123
- Tang, K., Guo, Y., Wu, L., Luo, Y., Gong, B., & Feng, L. (2021). A non-linear dose–response relationship between female body mass index and in vitro fertilization outcomes: A meta-analysis. Journal of Assisted Reproduction and Genetics, 38, 931–939. https://doi.org/10.1007/s10815-021-02082-8
- Wells, R. K., Torres, A., Mau, M. K., & Maunakea, A. K. (2024). Racial–ethnic disparities of obesity require community-specific biomedical research for Native Hawaiians and other Pacific Islanders. Nutrients, 16(24), 4268. https://doi.org/10.3390/nu16244268
- Decourt, C., Connolly, G. A. D. P., Ancel, C., Inglis, M. A., & Anderson, G. M. (2022). Agouti-related peptide neuronal silencing overcomes delayed puberty in neonatally underfed male mice. Journal of Neuroendocrinology, 34(10), e13190. https://doi.org/10.1111/jne.13190
- Converse, A., Zaniker, E. J., Amargant, F., & Duncan, F. E. (2023). Recapitulating folliculogenesis and oogenesis outside the body: Encapsulated in vitro follicle growth. Biology of Reproduction, 108(1), 5–22. https://doi.org/10.1093/biolre/ioac176