The present study was designed to investigate whether caffeine administered daily throughout the estrous cycle prior to fertilization affected the development of the subsequent preimplantation day 5 rat embryo. The viability parameters chosen for assessment were glucose utilization, cell number, and stage of embryonic development (morula to hatched blastocyst). Two independently replicated experiments were conducted. Together these experiments demonstrated that after fertilization, a proportion of affected oocytes maturing in a caffeine-perfused ovarian environment used and oxidised glucose at a significantly higher rate and were significantly more advanced developmentally compared with their litter mates or with the control counterparts. Cell number per embryo and the number of embryos recovered (litter size) remained constant, suggesting that caffeine, at the doses used, is unlikely to affect the ovulation rate or prevent fertilization. This study is significant because it demonstrates for the first time that a drug such as caffeine, when administered prior to ovulation and genomic activation, causes a quantitative difference in growth promoting energy utilization in a proportion of susceptible embryos after genome activation. A link between genomic imprinting and changed developmental program in the preimplantation embryos was suggested.

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PubMedDate not supplied

Effects of preconceptual caffeine exposure on pregnancy and progeny viability.

OBJECTIVE: A previous study demonstrated for the first time that a drug such as caffeine, administered prior to ovulation and genomic activation, causes a quantitative difference in growth-promoting energy utilization in a proportion of 5-day-old blastocysts. The objective of the present study was to investigate whether developmental changes induced by caffeine administered throughout the estrus cycle prior to fertilization are sustained throughout pregnancy and after birth. METHODS: Caffeine was administered to rats throughout the estrus cycle prior to fertilization, with control and experimental groups subdivided into preimplantation and postimplantation categories. Preimplantation fertilization rate was assessed on day 4 of pregnancy by a pregnancy-induced elevation in maternal plasma progesterone concentration, or by flushing each uterine horn on day 5 of pregnancy to determine the presence or absence of a litter. Postimplantation fetuses were collected on gestational day 12 or allowed to go to term. RESULTS: Preconceptual caffeine exposure significantly reduced maternal fertility by the failure of a proportion of the litters to implant, rather than curtailing preimplantation development or postimplantation losses. Postnatal mortality between weeks 0 and 1 was elevated and the weekly incremental growth rate of the pups from week 3 through week 7 was significantly reduced in the preconceptually caffeine-treated offspring. Experimental females reached puberty at the same age as the controls but at a significantly lower body weight. Gestation length, hirthweight, litter size, sex ratio, and anogenital distance (a measure of prenatal androgenization) were not affected by preconceptual caffeine treatment. CONCLUSIONS: It was concluded that the reduced fertility rate in preconceptually caffeine-exposed rats was due to the failure of litters to implant rather than to a reduced fertilization rate, which was normal. It was further concluded that the growth rate over the neonatal and prepubertal periods of surviving pups in the caffeine-treated group was subnormal.

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PubMedDate not supplied

Caffeine exposure in utero increases the incidence of apnea in adult rats.

Caffeine abuse during pregnancy may be a factor in the development of long-term breathing abnormalities. Therefore, the objective of the present study was to monitor adult breathing patterns after in utero exposure to caffeine. This was done by isolating episodes of apnea of more than 6-s duration from the breathing data as obtained by the Cotwatch breathing monitors adapted for rat use. The breathing record obtained over 6 consecutive days was expressed as daily weighted apnea-hypopnea density (WAHD) values. It was shown that administration of caffeine in moderate (30 mg/kg daily) or high (60 mg/kg daily) doses throughout gestation resulted in a significant dose-dependent increase in the WAHD value. The experimental offspring were significantly growth retarded in utero and their subsequent growth rates were also affected. The caffeine-exposed pups grew more slowly with growth plateauing at the same age, resulting in smaller adults. A link was suggested between infants with apnea of prematurity, when occurring after the first week, and an increased risk for later apnea and sudden infant death syndrome.

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