Linking Ovarian Reserve to Embryo Viability: Insights from Bovine Implantation Models Relevant to Premature Ovarian Insufficiency.
According to CDC (2021) statistics, the success rate of Assisted Reproductive Technology (ART) pregnancies declines with increasing maternal age. A decrease in ovarian reserve and oocyte quality is generally associated with advanced maternal age (AMA) in women. However, a subset of women exhibits altered ovarian function and low antral follicle counts (AFC) before the age of 35, accompanied by oocytes with diminished developmental competence. This condition, known as Primary Ovarian Insufficiency (POI), affects approximately 1–3% of women and is characterized by accelerated ovarian senescence, reduced follicle reserve, and hypofertility. Oocytes from women with POI display impaired developmental potential, yet the molecular mechanisms underlying this loss of competence remain largely unknown.
Oocyte quality significantly influences early embryonic survival, the establishment and maintenance of pregnancy, fetal development, and even the risk of adult disease. Developmental competence is progressively acquired during folliculogenesis, as the oocyte grows, and during the period of oocyte maturation.
Given the limited availability of human oocytes for research, animal models, especially those based on agriculturally and economically relevant species such as cattle, offer a valuable and translationally relevant approach to investigate these processes, with implications for both reproductive biology and livestock productivity.
In previous studies, we characterized a bovine model of POI. Our group observed that cows with ovaries containing fewer than 10 mid-antral follicles (2–6 mm in diameter) and lacking follicles ≥10 mm produced oocytes with reduced developmental competence. This condition appeared to involve multiple factors, including alterations in the endothelial nitric oxide synthase system, increased aneuploidy, and mislocalization of progesterone receptor membrane component 1 (PGRMC1) and Aurora kinase B during meiotic division. Moreover, a reduction in the number of mid-sized antral follicles was associated with molecular markers of premature ovarian senescence in dairy cows.
At the transcriptomic level, 2,223 differentially expressed genes (DEGs) were identified, encompassing pathways related to RNA processing and transport, protein synthesis, organelle remodeling, and cellular metabolism. A meta-analysis comparing bovine oocytes with datasets of young human oocytes at various maturation stages identified 315 conserved genes undergoing the GV–MII transition in both species, primarily associated with meiotic progression and cell cycle regulation. Gene expression analysis between GV and MII oocytes from POI-like cows revealed no significant transcriptomic differences, indicating a substantial failure to properly remodel the transcriptome in the POI model. Clustering analysis further suggested that the cow’s genetic background exerted a greater influence on gene expression than the oocyte’s maturation stage.
Taken together, these findings indicate that ovarian reserve plays a crucial role in determining oocyte developmental competence by influencing the surrounding endocrine milieu, mitochondrial function, and immune regulation.
Building upon these findings, my doctoral research aims to deepen the understanding of ovarian and embryonic competence in the bovine model through the following objectives:
1. Validate the relationship between ovarian reserve and embryo mortality.
2. Identify the developmental and molecular dialogue underlying implantation failure and its association with ovarian reserve.
3. Sequence embryos to identify key factors conferring implantation competence and establish a comprehensive transcriptomic profile.
4. Investigate specific subsets of Toll-like Receptors (TLRs) as potential modulators contributing to maternal recognition during early development.
My doctoral project is conducted as Doctoral Candidate 9 within the IMPLANTEU consortium, which aims to advance and transform our understanding of embryo implantation. This research is funded by the European Union’s Horizon Europe Research and Innovation Programme under the Marie Skłodowska-Curie Actions Doctoral Network (MSCA-DN).
I hold a Master of Science in Life Sciences from Mount Carmel College, Bangalore, India, graduating with an overall grade of A++ (First Class Exemplary). My master’s thesis focused on assessing the morphological, cytological, and biochemical responses to abiotic stress in two agriculturally relevant species. During my postgraduate studies, I assisted faculty members in authoring and proofreading three research publications, in addition to contributing to my own research work. I received specialized training at the National Centre for Biological Sciences (NCBS), India, where I gained hands-on experience in cell culture and advanced microscopy. Additionally, I completed training at BMCHRC, India, under the guidance of onco-pathologists, to gain an understanding of the molecular basis of Chronic Myeloid Leukemia (CML) and Acute Promyelocytic Leukemia (APL). I also hold a Bachelor of Science in Biology with triple majors in Zoology, Botany, and Chemistry, graduating with distinction in all three disciplines.
My main interests include translational research in cell and molecular biology.
Publications: Orcid
Supervisor Prof. Alberto Maria Luciano
Co-supervisor Prof. Valentina Lodde
