Monoclonal antibodies specific for rat relaxin. V. Passive immunization with monoclonal antibodies throughout the second half of pregnancy disrupts development of the mammary apparatus and, hence, lactational performance in rats.

There were two related objectives to this study. The first was to determine the influence of relaxin on development of the mammary apparatus (nipples and glands) during the second half of pregnancy. The second was to determine whether the relaxin-dependent development of the mammary apparatus was required for normal postpartum lactational performance. Both objectives were accomplished by neutralizing endogenous relaxin throughout the second half of pregnancy with a monoclonal antibody specific for rat relaxin (MCA1). MCA1 was administered iv to rats daily from days 12-22 of pregnancy. On day 22 the morphology of the mammary apparatus of MCA1-treated rats differed from that of controls; nipples were dramatically smaller, collagen fibers had significantly greater mean density and consistency, and elastin fibers had greater mean density, length, and interdigitation. In addition, the mean number of alveoli surrounding lactiferous ducts was significantly smaller in MCA1-treated rats than in controls. There were no differences between MCA1-treated rats and controls in the mean thickness of connective tissue surrounding ducts, the height or density of luminal cells lining lactiferous ducts, or the sizes of either adipocytes or arteries. To examine lactational performance, MCA1-treated and control rats were cesarean sectioned between 2100-2400 h on day 22 of pregnancy and given foster pups born of untreated intact donors. Although both MCA1-treated rats and control rats exhibited a high incidence of maternal behavior after cesarean delivery, mean pup weight and incidence of live pups declined markedly during days 1-5 of fosterage in MCA1-treated rats compared to controls. Furthermore, unlike controls, there was no observable postpartum nipple development in MCA1-treated rats by day 5 of fosterage. Mammary glands obtained from MCA1-treated rats on day 5 of fosterage had markedly lower mean weight than controls. This study demonstrates that passive immunization of endogenous relaxin throughout the second half of pregnancy disrupts development of the nipples and mammary glands in the rat. Moreover, it establishes that relaxin's effects on the development of the mammary apparatus during pregnancy are essential for growth and survival of the young during lactation.

Effect of relaxin on mammary development in ovariectomized pregnant gilts.

The role of relaxin in mammary development was studied between days 80-110 of pregnancy in ovariectomized gilts given progesterone to maintain pregnancy. To obtain an objective measurement of lobulo-alveolar (parenchymal) composition, mammary glands were cut in cross-section through the teat, and the area of parenchymal tissue on the exposed face of the gland was determined. Ovariectomy on day 80 or 100 followed by progesterone replacement therapy resulted in a dramatic reduction in the rate of growth of mammary parenchymal cross-section area on days 100 and 110 of gestation, respectively, compared to that in controls. In contrast, progesterone plus relaxin therapy, with highly purified porcine relaxin, restored the mammary parenchymal cross-section area to control values in ovariectomized gilts. Morphometric analysis of mammary tissue on day 110 of pregnancy indicated that both the absence of relaxin after ovariectomy and replacement therapy with porcine relaxin in ovariectomized gilts had little if any effect on the percentages of the lumen, stroma, or epithelial that comprised the mammary parenchyma. It is concluded that relaxin has a stimulatory effect on the growth of mammary parenchymal tissue during late gestation in the pig.