Down regulation of the estrous cycle in marmoset monkeys by GnRH-antagonist treatment

The marmoset monkey is an attractive new world primate model for early developmental questions due to its small size and unproblematic captivity behavior. However, superstimulation protocols used in oldworld monkeys and women are not successful in the female marmoset. A novel protocol is needed to utilize these new world monkeys as an efficient animal model to produce embryos for research. To create such a protocol we first examined the effects of long term estrous cycle control and secondly in a dose finding study, we determined the length of a down-regulation protocol with a GnRH-antagonist. Marmosets were grouped according to the number of estrous cycles which had been controlled. Application of PGF2α in the mid luteal phase led to an immediate onset of the follicular phase. The blood progesterone concentration rapidly declined and increased again on day 9–10. The rapid decline was comparable, indicating that all animals, independently of the number of controlled cycles, react similarly to multiple PGF2α injections. To determine the proper dosage for a GnRH-antagonist (cetrorelix), a group of 12 animals was treated with two different dosages. Cetrorelix was applied in the mid luteal phase, three times over two days. In both cetrorelix-treated animal groups the early progesterone levels matched the controls. In the low-dose treatment group (0.01mg/100g BW) the expected progesterone rise on day 10 was delayed between 9 to 15 days whereas in the high-dose treatment group (0.1mg/100g BW) the progesterone rise was delayed between 21 to 41 days. In the low-dose group the steepness of the slope from day 20 onwards is almost identical to that of the control group. This is reflected in the BioCG levels measured.

The results clearly show that the controlled ovarian cycle length and progesterone response is not altered by the number of PGF2α injections. Based on the GnRH-antagonist results a complete down-regulation in female marmosets can be achieved by applying a low-dose regimen and intrinsic gonadotropins would not interfere with the ovarian superstimulation protocol.