Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Ovarian sensitivity to gonadotrophins is increased by passive immunization against leptin (#178)

James R McFarlane 1 , Suresh Kumar Athiappan Palanisamy 1 , Muren Herrid 1
  1. Centre for Bioactive Discovery in Health and Ageing, University of New England, Armidale, NSW, Australia

Leptin originally thought to be derived predominantly from adipose tissue is now known  to be almost ubiquitously expressed in many tissues. The complete absence of leptin is not developmentally lethal and results in early onset obesity, stunted skeletal and brain growth, extreme insulin resistance, hyperphagia, a compromised immune system and infertility. In this study we examine the effects of passive immunization on ovulation rate and mRNA expression  of the leptin receptors in prepubertal mice.

Immature mice (3 weeks old) were divided into four groups (n=6) and given subcutaneous  injections of the following treatments on day 1 and day 3 (i) saline; (ii) anti-leptin antibody (50 µg); (iii) eCG (0.1 IU); (iv) eCG (0.1 IU) + anti-leptin antibody (50 µg). Animals were sacrificed by CO2 asphyxiation 24 hours after the last injection. Ovaries and uteri weighed, the eggs in the uterine tube ampulla were counted, and relative mRNA expression in the ovary of the leptin receptors were determined by qPCR.

There was no difference in ovarian and uterine weights between experimental groups except for the eCG + anti-leptin group ovaries which was significantly heavier than the control. A higher number of eggs were collected from the eCG + anti-leptin (16.1 ± 1.8) group compared to control (1.12 ± 0.02), eCG (0.8 ± 0.03) anti-leptin group (2.8 ± 0.09). The expression of the short forms of the receptor including the soluble form were significantly increased over the control by the passive immunization which was increased even further in combination with eCG, while the long form of the receptor was decreased. In summary, reducing peripheral leptin concentrations increases the sensitivity of the ovary to gonadotrophins and results in ovulation in the presence of otherwise non stimulatory concentrations of gonadotrophins.