الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Premature ovarian failure (POF) is a multifactorial reproductive disease that affects 1% of the female population and results in sub/infertility. While most cases are due to genetic causes and cannot be treated, 20% of the females suffering POF are resultant from chemotherapy induced ovo-toxicity.
Owing to the disturbed folliculogenesis, POF is characterized by low estradiol levels, high FSH and LH levels with or without amenorrhea. Low anti-Mullerian hormone (AMH) levels additionally reflect the diminished ovarian reserve associated with the condition. Understanding the molecular, genetic and hormonal mechanisms that govern folliculogenesis poses hope for identifying follicle preservation strategies to save the ovaries and hence fertility.
The ovarian cycle is chiefly controlled by the hypothalamus and pituitary hormones once the follicles reach a certain size and become Gonotrophin-responsive. Prior to large antral follicle formation, follicles grow from a pre-formed pool of oogonia (developed embryonically) into primordial follicles (PMF), primary (PF) and secondary follicles. The early stages of folliculogenesis are regulated by several genes and ovarian derived growth factors. The architectural arrangement of somatic cells that surround the oocyte is also vital for the crosstalk between the oocyte and granulosa cells, sustaining the survival of the ovary. Through this arrangement, positive and negative regulatory mechanisms govern the transition from PMF to primary follicles.
AMH, a glycoprotein hormone secreted from the GCs of growing antral follicles, serves as a main negative regulator of PMF to PF activation, and acts as a brake mechanism against over activation of the resident PMF pool. AMH levels decrease with age and ovarian damage while increase in polycystic ovarian syndrome. PI3K/PTEN/AKT is another suppressive molecular pathway employed to guard the PMF against overactivation. PTEN is a pro-apoptotic protein that negatively regulates this pathway. Moreover, although apoptosis primarily controls several aspects of ovarian development and cyclic function, it is enhanced when chemotherapy (CTx) activates the death receptors, leading to increase in tissue Caspase 3 levels and eventually cell death.
Much research has focused on discovering methods of fertility preservation; however, fewer were dedicated to protection against CTx induced ovarian damage and restoration of follicular function following CTx cessation. Stem cells have attracted massive attention in the field of regenerative medicine for their potential to rejuvenate cells after insult and rescue organs from failure. Nevertheless, restoring lost germ cells using stem cells is debatable in the field or reproductive biology due to the central dogma of females being born with a fixed ovarian pool of PMFs that cannot be re-filled. Recently, researchers have been experimenting in-vitro gamete differentiation using embryonic stem cells as the main source. Our study leveraged a primitive source of stem cells from the shed fetal cells in the amniotic fluid. Pivoting away from the controversy of creating novel germ cells and follicles, our study aimed at using the powerful paracrine regenerative capacity of AFSCs on targeting specific genes and molecular pathways coordinating the ovarian physiology.