Relation of parity and estrous cyclicity to the biology of pregnancy in aging female rats

In the female rat, the incidence of regular estrous cyclicity and fertility decreases progressively during aging, and the causes for these are unknown. To reveal the biology of pregnancy in aging rats, we performed a longitudinal study in a colony of multiparous rats bred every 2 mo. Beginning at 4 mo and continuing to 12 mo of age in these same individual females, we determined the chronological changes in estrous cyclicity, examined the relationship between the estrous cycle pattern and fertility, and recorded the numbers of live and dead pups delivered at term. In separate groups of 4- to 12-mo-old multiparous rats, we counted the number of ova present in the oviducts (ovulation rate) one day after mating and the number of grossly normal blastocysts found in the uteri on Day 5 of pregnancy. Similar studies were also performed in primiparous rats of 8, 10, and 12 mo of age. The cessation of regular cyclicity during aging occurred significantly (p less than 0.01) earlier in virgin than multiparous rats. Fertility followed a similar but more dramatic pattern of decline than did the incidence of regular cyclicity in both the multiparous and virgin females. Few irregularly cyclic and persistent-estrous females had fertile gestations after mating, and increasing proportions of regularly cyclic females also failed to reproduce successfully at middle age (8-12 mo). Thus, regular ovulatory cycles were essential but not sufficient for fertile gestations in aging rats. Beginning at 6 mo of age, the litter sizes of multiparous rats decreased progressively, and these decreases were associated with a similar decline in the number of live but not dead pups delivered. Also, the percentage of dead pups/total number of pups delivered increased steadily during aging in multiparous (from 14% to 69%) but not primiparous females. The litter sizes of 8- to 10-mo-old primiparous females were not different from those of multiparous rats. However, the litter sizes of irregularly cyclic rats were consistently smaller than those of regularly cyclic females. Thus, parity had little effect on fecundity in aging females, whereas the cessation of regular ovulatory cycles during aging greatly decreased both the incidence of fertility and the litter size.(ABSTRACT TRUNCATED AT 400 WORDS)