An Abnormal Pattern of Embryonic Development during Early Pregnancy in Aging Rats1

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Abstract
There is recent evidence that a decline in fertility and litter size precedes the cessation of regular estrous cyclicity in middle-aged female rats. This decline in litter size is related to a decrease in the number of normal blastocysts that are present on Day 5 of gestation, immediately prior to implantation. Thus, the pattern of embryonic development duirng the first 5 days of pregnancy may be altered in middle-aged rats, resulting in fewer implanting embryos and smaller litter sizes. The present study examined the ovulation rates, fertilization rates, and the patterns of embryonic development in regularly cyclic, young and middle-aged females during the first 5 days of pregnancy. Examination of the numbers of ovulated ova revealed that the ovulation rate was significantly reduced in 12- to 14-mo-old females (13 mo; 9.0 .+-. 1.0/rat), but not in 9- to 11-mo-old females (10 mo; 12.2 .+-. 0.8/rat), as compared to that in young animals (12.8 .+-. 1.0/rat). However, there was no decrease in fertilization rate in either the 10-mo or 13-mo group. While the total numbers of embryos present on Days 2 - 5 were similar among all 3 groups, embryos from 10-mo females displayed a delayed pattern of development and an increased incidence of morphological abnormalities. These changes in embryo development were even more pronounced in the 13-mo group. By Day 5 of pregnancy, there was a significant reduction in normal blastocysts in 10-mo (7.3 .+-. 1.2/rat) and 13-mo (6.0 .+-. 1.6/rat) rats, as compared to young females (10.6 .+-. 0.9/rat). These data reveal that the decreased numbers of normal blastocysts in middle-aged rats result from delayed and abnormal patterns of embryonic development, possibly reflecting impaired oocyte quality and/or alteration in the oviductal environment during aging.