27 - 30 May 2005

EFFECTS OF EXOGENOUS GONADOTROPIN ADMINISTRATION ON FOLLICULAR GROWTH AND OVULATION IN ob/ob AND db/db MICE M-L Alvarez Gonzalez [1], A Pintiaux [1,2], P Monget [3], F Frankenne [1] and JM Foidart [1,2] [1] Laboratory of Tumor and Development Biology Ulg, Belgium [2] Department of Gynaecology and Obstetric CHR-Citadelle Liège, Belgium [3] INRA Nouzilly, France

Leptin is an essential hormone in regulating satiety and weight balance. From mice models and rare human clinical cases, leptin is known to be important for reproduction. An hypothalamic role has been described but its potential direct impact on the ovary function is unknown. Particularly, wether or not leptin activity at the ovary level is required for ovulation to occur still remained an unanswered question.
Both the leptin gene deficient (ob/ob) and the leptin receptor gene deficient (db/db) models are characterised by a morbid obesity with a sterility in females and males.

In this work, we first studied the folliculogenesis in females ob/ob and db/db mice after 1, 2, 3 or 4 injections of exogenous gonadotropin (PMSG). From the first injection, a vaginal opening and a marked increase in ovarian and uterus weight were observed. The follicles that developed with PMSG treatment were very similar to those seen in normal C57Bl/6j mice. However, atresia was largely decreased by treatment. A corpus luteum was also observed as soon as after two injections of PMSG, strongly suggesting ovulation has occurred.

In a second experiment, we treated ob/ob and db/db mice with a single injection of PMSG followed 48h later by an injection of hCG. Mice were than mated with reproductively proven males and sacrificed after 38h. Ovulation was assessed by counting the number of ova. Further to this treatment, all mice were showed to have ovulated. However, none were fertilized, despite sexual behaviour was normalised.
These data show that exogenous gonadotropin is able to restore the ovulation lost further to leptin or leptin receptor deficiency.

This strongly raises the hypothesis that the known leptin dependency of ovulation is essentially due to the permissive/stimulating action of leptin on gonadotropin production at the hypothalamus/hypophysis level.

List of abstracts from the 3rd International Conference on the Female Reproductive Tract