The intrauterine environment induces developmental adaptations that impact health and disease risk later in life. Reproductive abnormalities are now included in the long list of health complications seen in offspring exposed to early life adversity including poor prenatal nutrition. Previous work has shown using a rat model, that offspring born to mothers that were nutrient restricted (UN) during pregnancy are growth restricted, enter puberty early, and as adults, display characteristics of early ovarian aging with reduced follicle number. This present study aimed to investigate whether key proteins involved in ovarian follicle recruitment and growth, including the PI3K/Akt pathway, may be impaired as a result of early life nutritional adversity. Maternal UN resulted in irregular estrous cyclicity due to persistent estrus, a significant decrease in young adult ovarian antral follicles, corpora lutea, and a significant increase in atretic follicles. A decrease in growing follicles in UN offspring appears to be due to lowered expression of granulosa-cell secreted growth factor IGF-1 in antral follicles, and increased expression of pro-apoptotic factor Casp3 in secondary follicles of young adult offspring born to UN dams. Changes in follicle signalling pathways were apparent before observing altered ovarian function. In UN prepubertal offspring, expression levels of IGF1-R and FSHR were lowered in secondary and antral follicles respectively. These growth factors may contribute to a decrease in PI3K/Akt activation as immunohistochemical staining revealed a decrease in pAkt immunolocalization in prepubertal antral follicles. Moreover, neonatal ovaries of UN offspring show decreased levels of immunopositive staining for AMHRII, a regulatory receptor of the ovarian reserve. This study demonstrates that maternal UN during pregnancy impacts ovarian function in female offspring as early as P65. Findings from this study provides a model of understanding mechanisms of follicle loss and reproductive dysfunction as a result of nutrient restriction during fetal life. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/18053 |
| Date | 11 1900 |
| Creators | Chan, Kaitlyn |
| Contributors | Sloboda, Deborah, Biochemistry and Biomedical Sciences |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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