Isoforms of eCG in reproductive physiology & factors which influence gonadotrophin signaling

Abstract

Equine chorionic gonadotrophin (eCG) is a placental hormone produced during the first third of gestation in mares, and exists in a range of isoforms. At approximately 30 days of gestation, eCG becomes detectable in circulation and peaks around 60 days, thereafter declining to undetectable concentrations by around 120 days. The functions of eCG include revival of the ovarian corpus luteum which sustains progesterone production supporting the pregnancy until placentally-derived steroid production is sufficient. One unusual characteristic of eCG is the dual LH and FSH activity it possesses. For this reason, eCG is harvested from pregnant mare plasma, isolated, and concentrated to formulate commercial gonadotrophin products which are used extensively in assisted reproductive technologies in agricultural livestock. A large proportion of the eCG product market comprises the sheep industry. A major complication with the use of commercial eCG is the considerable variation in bioactivity between batches as well as in individual animal responses to treatment which may lead to insufficient stimulation or superovulation with negative consequences on embryo survival. It was therefore a prerogative to investigate the isoform composition of eCG and how this impacted on the bioactive properties both in vivo and in vitro. The research findings in this thesis show an expansive range of very acidic to very basic eCG isoforms circulating in mare plasma. When eCG isoforms were collectively analysed in three groups (acidic, intermediate, and basic), isoforms had greater acidity prior to and during the eCG peak, but thereafter experience a substantial drop in hormone concentration and acidity, with significantly increased intermediate isoforms. Within the acidic group, the most acidic fraction showed greatest percentage composition prior to the eCG peak. The differences in isoform composition may be indicative of altered function and numerous studies have shown that pituitary gonadotrophin isoform composition has a major impact on bioactivity.