Biomolecules of Human Female Fertility - Potential Therapeutic Targets for Pharmaceutical Design

Abstract

Scientists are able to advance the frontiers of human reproduction by employing a variety of molecular biological techniques to understand the biological processes intricately linked to oocyte and ovarian follicle development. Despite an abundance of knowledge concerning essential pathways which may have critical roles in oogenesis and folliculogenesis, the repertoire of medications to treat female fertility problems remains limited to a few classes of drugs involved in the induction or suppression of folliculogenesis and ovulation; many of which are not specific in their drug actions and can give rise to complications during clinical application. This paper aims to review biomolecules and pathways (e.g. PI3K, WNT, MAPK) pertinent to ovarian follicular development and active in human oocytes, including those involved in communication between somatic cells within the ovary (cumulus cells, granulosa cells and thecal cells) and the oocyte itself. These biomolecules which are involved in the nuclear and cytoplasmic maturation of oocytes and the control of ovarian folliculogenesis have potential as targets for improved ovarian stimulation, optimisation of oocyte maturation, and as biomarkers of oocyte viability assessment.

Are the pituitary gonadotrophins determinants of complete molar pregnancy? An investigation using the method of least squares

“…The hypothesis that circulating FSH is a determinant of complete mole is biologically plausible as FSH is intimately involved in oocyte and follicular maturation, including the resumption of meiosis I. 2 , 7 …”

“… 1 Ovulation with follicular maturation and completion of meiosis I is driven by follicle stimulating hormone (FSH) and luteinizing hormone (LH) whose plasma levels vary according to the stage of the menstrual cycle and maternal age. 2 The maternal age-specific incidence of complete mole (ICM) is bimodal with a minor peak in teenagers, a minimum in the mid-thirties and a higher maximum in mothers over 40 years. This pattern is universal but remains unexplained.…”

The transcriptome of follicular cells: biological insights and clinical implications for the treatment of infertility

“…The oocytes then enter a protracted stage of arrest, known as dictyate, and remain there until meiosis is resumed. This takes place with the onset of puberty in females and the initiation of the menstrual cycle (reviewed in Huang et al, 2012). Under the influence of gonadotrophins [follicle stimulating hormone (FSH) and luteinizing hormone (LH)], MI is resumed, the oocyte progresses to metaphase I, chiasmata are resolved and homologous chromosomes separate, one set (n ¼ 23) remains in the oocyte, while the other enters the first polar body (PB) (reviewed in Sutton et al, 2003;Fragouli et al, 2011).…”

Mdm2‐p53‐SF1 pathway in ovarian granulosa cells directs ovulation and fertilization by conditioning oocyte quality

“…Cumulus granulosa cells determine oocyte quality and control oocyte maturation in the periovulatory period, which is essential for successful ovulation and fertilization. Thus, molecular and cellular events in the cumulus granulosa cells regulating oocyte maturation need to be elucidated for improvement of medical treatment to infertility, as well as development of a new approach for fertility control (4).…”