Dietary restriction permits normal parturition and lactation but suppresses mouse mammary tumor virus proviral transcription even after mammary involution

Dietary restriction of C3H/Ou mice prevents development of spontaneous mammary adenocarcinoma by suppressing mammary expression of the mouse mammary tumor virus (MMTV) via a mechanism which may involve prolactin. In the present study, dietary restriction of 40% was imposed for 16 weeks on nulliparous C3H/Ou mice, interrupted by ad libitum consumption at mating and continued only during pregnancy and lactation, with 40% energy restriction reimposed at the end of lactation. The results show that mammary MMTV mRNA expression levels of chronic energy intake restricted (CEIR) mice and ad libitum fed mice are similar and elevated during early lactation, when all mice of both groups are being fed ad libitum energy levels. In spite of this, and in marked contrast, when CEIR dams are returned to 40% dietary restriction following the weaning of litters, mammary MMTV transcription is suppressed to levels 4-5-fold less than those measured in mammary glands from ad libitum fed controls. Within the 38 weeks of study, 73% of ad libitum fed uniparous mice at risk and 11% of CEIR uniparous mice at risk developed mammary tumors, yet mice of both dietary groups delivered and weaned healthy litters with comparable efficiency. When dietary restriction is maintained in CEIR mice during pregnancy and lactation, efficiency of conception and litter size are reduced, and MMTV transcription is suppressed even during lactation. Mean serum prolactin levels were not significantly different among dietary groups. These findings show that the level of MMTV transcription is rigorously influenced by dietary energy level, and that 40% dietary restriction of C3H/Ou mice not only suppresses mammary MMTV transcription and prevents mammary tumor development in uniparous mice, but also permits normal conception, gestation, lactation, and the production of healthy litters as long as the nutritional demands of gestation and lactation are met.