Reproductive ageing and the menopause

This brief review describes early work initiated by Anne McLaren and John B iggers, in which they repeated on mice a very early experiment carried out by John Hunter on pigs, to test the effect of unilateral ovariectomy on sub sequent breeding performance. This and subsequent experiments led to the co nclusion that reproductive ageing in the female mouse was largely due to ag eing changes in the uterus. Asa result of these changes fewer implanted bla stocysts are carried to term in the older females, with the result that the size of litters produced gradually drops and ceases altogether well before the expected time of death, thus leading to a period of reproductive inact ivity at the end of life. Other organs undergo ageing changes but it appear s to be those in the uterus which limit reproductive performance in the fem ale. The somatic organs concerned in bringing the male gametes into the env ironment are still able to function effectively almost until the time of de ath so that males have a very short period of reproductive inactivity at th e end of their lives. Due to the prenatal onset of meiosis in the germ cell s, female mammals and some, but not all, other vertebrates are born with a finite crop of oocytes in the ovary, which cannot be increased after birth. Nevertheless, with the exception of women, female mammals appear to be abl e to produce ova well into old age, and have them fertilized. When examined after death the ovaries still contain oocytes so this is not a limiting fa ctor in reproduction in old females. In women the situation is completely d ifferent. They also have an extended period of reproductive quiescence in m iddle and old age, the menopause, but, unlike other female mammals, this is not due to failure of the uterus but is caused by the ovary becoming deple ted of oocytes in middle age. The reason women run out of oocytes before th e end of life, whereas the other mammals which have been studied do not, is associated with the greatly extended lifespan of humans compared to other mammals of equivalent size. There is a linear relationship between longevit y and body weight in mammals, small mammals have much shorter lives than la rge ones. This is probably associated with the increased production of free radical oxygen necessary to maintain body temperature in smaller animals. Heat is lost through the body surface which becomes relatively less as the animal increases in weight, so the smaller animal has to metabolise and thu s produces more free radical oxygen to maintain body temperature. For reaso ns unknown this seems not to apply to humans. The menopause has thus evolve d as a consequence of two adaptations: the prenatal onset of meiosis, commo n to all mammals and many other Vertebrates a nd the greatly increased long evity of all humans, both male and female. In View of this dual origin it i s unlikely to have evolved in response to an adaptive need to have grandmot hers to help rear the young, as has been suggested!.