Effect of Maternal Age on Postimplantation Reproductive Failure in Mice

Abstract

Summary. Postimplantation reproductive failure was studied in young adult, 9-, 11-, 13-and 15-month-old C57BL/6J mice. Loss of all implanted embryos between the 8th and 18th days of pregnancy increased with advancing maternal age. The percentage of individual postimplantation deaths increased from 9% in young adults to 23% in 9-month-old mice and further increased to 45% in 11-month-old animals. Evidence is presented that deaths most commonly occurred in the early postimplantation period. Harman & Talbert (1970) showed that there was a marked decline in the number of implantation sites in the uterus of C57BL/6J mice associated with increasing maternal age. This decline began when the mice were 8 to 9 months old and continued until about 15 months of age, when implantation sites were found in only a small percentage of mice which were known to have mated.The present investigation is an extension of this work and was designed to study the influence of maternal age on the survival of embryos and foetuses of this strain of mice between the 8th and 18th days of pregnancy.Female mice of the C57BL/6J strain were obtained from the Jackson Memor¬ ial Laboratory, Bar Harbor, Maine. Ageing animals were retired breeders, each of which had delivered a minimum of three litters before they were received in this laboratory. Young adult control mice were obtained from the same source and delivered one litter before inclusion in the study.Ageing female mice and young adult controls were placed with young adult AJ-strain males late in the afternoon and were examined for the presence of a vaginal plug before 10.00 hours the following morning. Females that mated were isolated and laparotomy under Avertin anaesthesia was performed 7 days later. The number and location of implantation sites in each uterine horn were observed through a mid-ventral incision. Care was taken not to handle the implantation swellings. The incision was closed in the pregnant mice and they were killed on the 18th day of gestation. At this time, the number of foetuses and résorption sites in each horn were noted and each foetus was examined with a dissecting microscope for evidence of externally visible anomalies. The ovaries were prepared for histological study.Animals in which no implantation sites were found at laparotomy on the 8th 449

Reproductive Efficiency in Aged Female Rabbits Given Supplemental Progesterone and Oestradiol

“…Our findings that the decline in reproductive capacity was not primarily due to a reduction in ovulation rate agrees with reports in the hamster (Thorneycroft & Soderwall, 1969) and in some rodents (Talbert, 1968). Aged does at 12 and 24 days post coitum had 71-3% and 76-7% as many CL, 48-4% and 45-6% as many implantation sites and only 14-0% and 20-0% as many viable embryos, respectively, as did the young does ( Table 2).…”

“…A reduction in the number of total follicles and an increase in atretic follicles with increasing age has been noted in several species (Talbert, 1968). The larger number of follicles in young rabbits, particularly towards the end of the gestation period, has previously been reported (Adams, 1968) and may be important in maintaining CL function through oestrogen production (Keyes & Nalbandov, 1967 (1970) reported that prenatal loss in rabbits mainly occurred after Day 10.…”

“…Reproductive capacity is initiated at puberty, increases for a short time, and eventually decreases at a rate characteristic of the species (Krohn, 1964;Schultze, 1967;Talbert, 1968). It has been suggested that the decline in fecundity with age might be due to (1) an exhaustion of the oocyte population (Ingram, Mandi & Zuckerman, 1958), (2) an increase in the incidence of defective oocytes (Henderson & Edwards, 1968) and (3) a decline in the ability of the uterus to maintain pregnancy (Adams, 1964(Adams, , 1970Biggers, 1969).…”

Ovarian Support of Pregnancy in Ageing Inbred Mice

“…Progesterone was found to have a significant effect but the oestrogen effect was not significant. (Harman & Talbert, 1970), although such changes could be a result of pregnancy loss (Talbert, 1971), and the histological assessment of luteal function is not reliable (Finn, 1970 (Finn, 1963) or by giving orthotopic ovarian grafts from young mice (Krohn, 1966). Measurements of plasma progestins in the hamster (Blaha, 1971) and in the rabbit (Spilman, Larson, Concannon & Foote, 1972) have shown that hormone levels are similar in young and old animals, except when there were no viable fetuses late in pregnancy (Spilman et al, 1972), and supplementary progesterone and oestrogen did not increase embryonic survival in old rabbits (Larson, Spilman, Dunn & Foote, 1973).…”

In vivo visualization of uterine mast cells by two-photon microscopy

“…These mice were then housed at the Central Animal Facility at the Otto-vonGuericke University Magdeburg, Medical Faculty, with a 12 h light:12 h darkness cycle. In all experiments, mice at the age of 10-16 weeks were used to avoid age-dependent influences on their reproductive phenotype (Talbert 1971, Parkening et al 1978, Holinka et al 1979. All procedures were in accordance with the institutional guidelines of Magdeburg, and the study was previously approved by the Landesdirektion Dessau (42502-2-978 Magdeburg).…”