Gynecology & Obstetrics
Open Access
ISSN: 2161-0932
ISSN: 2161-0932
Kajal Sihag
AIIMS, New Delhi
Scientific Tracks Abstracts: Gynecol Obstet
Mitochondria are essential for oocyte development, serving as the primary source of ATP through the β-oxidation of fatty acids via the mitochondrial fatty acid shuttle (MFAS). Key components of this pathwayâ??CPT1, CPT2, CACT, OCTN2, and L-carnitineâ??facilitate energy production crucial for spindle assembly, chromosomal segregation, and meiotic progression, all of which determine oocyte competence and embryo development. Despite its importance, the role of MFAS dysfunction in the onset and progression of premature ovarian insufficiency (POI) remains poorly understood. This study aimed to (1) identify genetic variants in MFAS-related genes in women with idiopathic POI using our custom analysis pipeline. The functional impact of mitochondrial variants on protein structure and function was assessed through a combination of in-silico prediction tools, including CADD, SIFT, PolyPhen-2 (PP2), CONDEL, and FATHMM. Additionally, protein modeling and structural visualization were performed using PyMOL and ProteinPaint to evaluate potential alterations at the molecular level and (2) evaluate the impact of MFAS inhibition on ovarian and systemic health using mouse models. Whole Exome Sequencing (WES) of POI patients uncovered novel variants in the OCTN2 transporter gene (SLC25A5), CPT1A, CPT1B, and CPT2, along with two novel pathogenic mitochondrial variants (ARHGEF28, AOX1) and multiple variants of uncertain significance in genes regulating mitochondrial function and the cell cycle. To investigate functional relevance, adolescent C57BL/6 mice were treated with MFAS inhibitorsâ??Etomoxir, Omeprazole, Mildronate, L-Amino Carnitine, Etoposide, and Cyclophosphamide. These models exhibited hallmark POI features, including reduced body weight, ovarian shrinkage, decreased follicle count, and increased follicular atresia. Elevated FSH levels confirmed POI induction. Moreover, liver, kidney, and spleen histology revealed systemic metabolic disturbances following MFAS disruption. In conclusion, the findings implicate MFAS dysfunction and mitochondrial defects as key contributors to POI pathogenesis. This study highlights POI as a metabolic disorder, urging deeper exploration of mitochondrial pathways for early diagnosis and fertility preservation.
Kajal Sihag is a PhD scholar in Reproductive Biology at AIIMS, New Delhi, currently researching mitochondrial fatty acid shuttle-mediated ER stress in premature ovarian insufficiency (POI). With over five years of research experience, She had developed expertise in exome sequencing, micromanipulation, and handling of gametes (sperm and oocytes). Her academic background includes an MSc in Reproductive Biology and Clinical Embryology from AIIMS and a BSc in Life Sciences from Delhi University and published multiple research articles and presented my work at national and international conferences, receiving recognition for my contributions. Kajal Sihag skilled in molecular biology techniques, cytogenetics, and working with animal models. She an active member of professional societies such as SMRM, SRBCE, and AIRSA. She highly adaptable, eager to learn, and passionate about advancing reproductive health through research and innovation.