Franke studied relatively young subfertile rats. Although the pituitary gland and ovaries of these rats still functioned normally, their brains had already started to function differently. This led Franke to conclude that the ageing of the brain reduces fertility.
Generally speaking, human brains regulate the reproductive system in the same manner as rat brains. However, an important difference is that rats still posses a significant number of oocytes after the fertile period, whereas in humans the supply is considerably depleted. This reduced supply of oocytes is the most important limiting factor for fertility in older women.
Despite this difference between humans and rats, the researcher still expects that the ageing of the brain in humans also plays a role in age-dependent reduced fertility. This knowledge could help to develop treatments for relatively young women who are subfertile. The fertility of women decreases from about the age of 30 years onwards. This can be problematic for women who wish to have a career before they have children.
Ovulation of oocytes is one of the reproductive cycle factors that is regulated by the brain. An initiating signal from the brain instructs the pituitary gland to produce more luteinising hormone (LH). A feedback mechanism from the ovaries to the brain ensures that ovulation only occurs when the follicles and oocytes are mature. Matured follicles produce large quantities of oestrogen. The brain responds to this and initiates ovulation.
The researcher revealed that this feedback mechanism no longer functions optimally in older female rats. Although the oestrogen concentrations in the blood had not changed with age, less receptors for oestrogen and progesterone were present in specific areas of the brain. Furthermore, older rats released less LH than younger rats.
High oestrogen concentrations normally lead to an increase in the number of progesterone receptors. These receptors are crucial for the occurrence of the peak in LH release. Older brains seem to be less sensitive to oestrogen. As a result of this, the LH peak attenuates and the fertility decreases.
For further information please contact Dr Annelieke Franke (Human and Animal Physiology Group, Wageningen University), tel. 31-317-482-199, e-mail: A.Schepens-Franke@anat.umcn.nl or assistant supervisor Dr Eline van der Beek tel. 31-317-467-853. The doctoral thesis was defended on 22 September 2003. Dr Franke's supervisor was Prof. V.M. Wiegant.
The research was funded by the Netherlands Organisation for Scientific Research.