Quantitative and ultrastructural characteristics of immunocompetent cells in the mammary gland during pregnancy and lactation

The quantity and ultrastructure of immunocompetent cells (ICC) were evaluated in the of rat mammary gland in dynamics of pregnancy and lactation. ICC found between the alveolar epithelial cells were represented by monocytes, small and medium lymphocytes, including some granule-containing lymphocytes. The quantity of ICC was found to increase in dynamics of pregnancy and to reach a its maximum on day 3 of lactation. This was accompanied by the appearance of macrophages and plasma cells. Similar changes were found in stromal ICC. It is suggested that quantitative and structural dynamics of mammary ICC is associated with provision of immune reactivity of the newborn and its adaptive immunity.     

Mechanism of regression of mammary gland carcinoma in lactating rats

The effect of the conditions of lactation on the frequency of regression of a transplantable mammary gland carcinoma RMK-1 was studied in albino rats. In rats feeding 8±1 young the tumor underwent regression in 47% of cases. After ovariectomy and administration of cortisone and oxytocin, which have an indirect inhibitory action on the secretion of FSH by the pituitary, the frequency of regression of tumors in rats feeding the same number of young rose to 71–81%. In rats with prolonged lactation, feeding 8±1 young for 2–2.5 months, and in rats with intensive lactation feeding litters of 13±2 young, regression of the tumors did not increase. The results confirm the validity of the hypothesis that, besides high secretion of pituitary FSH, a decrease in the secretion of pituitary LH plays a role in the regression of mammary gland carcinoma in the course of lactation.Oncologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR L. M. Shabad.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 5, pp. 582–585, May, 1978.     

Ultrastructural identification of Ia positive dendritic cells in the lactating rat mammary gland

Summary Dendritic cells which express Ia antigen have been demonstrated for the first time in the lactating rat mammary gland. Ultrastructurally, the dendritic cells appear as electron-lucent pale cells interspersed among the epithelial cells of the alveoli, forming a cell population distinct from classical macrophages. They show morphological resemblance to the dendritic cells of lymphoid organs as well as the Langerhans cells of skin. The Ia antigen has been localised by electron microscopic immunocytochemistry on the cell membrane and endocytotic vesicles and tubules. Ia positive cells are also seen in the stroma of the mammary gland. It is proposed that the dendritic cells of the mammary gland belong to the lineage of epidermal Langerhans cells and lymphoid dendritic cells, subserving an immunological role in the lactating breast.     

Cell kinetics in the small intestine of suckling rats I. Influence of hypophysectomy

Cell kinetics have been examined in the duodena of intact rats at 6, 16, and 22 days of age, and of hypophysectomized rats at 22 days. In intact rats the crypt population per villus increases more than 10-fold, the greater part of the increase occurring late in the third week. The labelling index does not differ between 6 (28.3%) and 16 (27.6%) days, but increases to 37.8% at 22 days. Generation time also does not differ between 6 (18.0 hours) and 16 (17.7 hours) days, but falls to 10.8 hours at 22 days by shortening of both the presynthetic and synthetic phases. Acceleration of cell migration rate between 18 and19 days of age results in shortening of cell transit time from seven days in rats younger than 18 days to two days in those older than 18 days. When rats are hypophysectomized at six days, the duodenal crypt population per villus at 22 days is comparable to that of intact rats at 16 days. The labelling index at 22 days is 19% below that of intact rats at six days. Generation time at 22 days is slightly shortened by a decrease of the presynthetic phase, but the duration of 15.5 hours is 43% longer than in intact rats at the same age. Despite the small crypt population and the low cell production rate, the cell-transit time in 22-day-old hypophysectomized animals is only three days.     

Endocytosis by absorptive cells in the middle segment of the suckling rat small intestine

In neonatal suckling rats, the absorptive cells of the duodenum, jejunum and ileum endocytose maternal milk macromolecules, including antibodies from the lumen. To determine whether the absorptive cells from the middle segment of small intestine have an apical endocytic membrane system that is the same as that of the duodenum, jejunum or ileum, we applied horseradish peroxidase by intraluminal injection, and examined the absorptive cells using light and transmission electron microscopy. In the middle segment of the small intestine, the absorptive cells had an apical endocytic membrane system including apical coated pits, apical invaginations, coated vesicles, vesicles, tubules, early endosomes, late endosomes and a large homogeneous electron-dense lysosome at the supranuclear region. This would suggest that the endocytic membrane system in the absorptive cells from the middle segment of the small intestine is specialized for quick and active intracellular digestion. The apical endocytic membrane system of the absorptive cells varied according to the segment of the small intestine, and the absorptive cells made their transition gradually from jejunal type to middle type, and then from middle type to ileal type at the suckling stage. The jejunal and ileal type of absorptive cells increased with growth, in contrast to the middle type.     

The effects of cortisol and BUDR on cellular differentiation in the small intestine in suckling rats

In suckling rats absorptive cells in the distal two-thirds of the small intestine ingest colloids by pinocytosis. In the middle third of the intestine pinocytosis ceases 17 to 21 days after birth and can be halted prematurely by glucocorticoids. The adrenal cortex is relatively inactive in newborn rats and begins to secrete glucocorticoids two weeks after birth; this secretion has been suspected to cause the termination of pinocytosis. Glucocorticoids do not stop pinocytosis in absorptive cells already present on the villi but induce the renewing population of cells in the crypts to replace the cells on the villi with new ones that do not engage in pinocytosis. Therefore, glucocorticoids act by inducing a new direction of cellular differentiation. BUDR (5-bromodeoxyuridine) is reported to inhibit cellular differentiation reversibly in vitro. When injected into 8 to 9-day-old rats, simultaneously with cortisol, it inhibited the change in cellular differentiation induced by cortisol; that is, pinocytosis continued unabated. BUDR did not appear to be toxic and did not interfere with cellular replacement in the small intestine, as judged autoradio-graphically. Thus it appears that BUDR inhibits the initiation of cellular differentiation by cortisol but does not interfere with cellular proliferation or the pre-established program of cellular differentiation that leads to pinocytosis. The mechanism of action of BUDR is still unknown; it is discussed in light of the possibility that BUDR may after cellular differentiation without acting directly on the genome.     

Influence of taste stimulation during the suckling period on adult taste preference in rats

Effects of taste deprivation and selective taste exposure during the suckling period on adult preference for flavored solutions was examined. Taste deprivation was achieved by rearing rat pups "artificially," in individual cups with intragastric feeding from Postnatal Days 4 through 17 or 18. In the first study the effects of artificial rearing on male Long-Evans rats were examined. In the second study female Wistar rats were exposed to a single tastant, sucrose, which was introduced on a background of taste deprivation. Results of both studies were similar. No differences in taste sensitivity or preference were detected between animals subjected to taste deprivation or selective taste exposure and their normally reared littermates. These results suggest that suckling stimulation is not necessary for normal taste development and that the taste system of the rat is not particularly susceptible to the influence of early experience. Other interpretations of these results are also discussed.     

Albumin transcytosis across the epithelium of the lactating mouse mammary gland

Murine milk contains 18 mg ml⁻¹ serum albumin, a concentration equal to that in the serum of the lactating mouse. We examined cellular transport using in vivo methods in the mouse. At steady state the specific activity of ¹²⁵I-albumin injected into the blood stream was equal in plasma and whey, confirming that milk albumin is extra-mammary in origin. Fluorescent albumin crossed the gland from basolateral surface to lumen via cytoplasmic vesicles, but was not transported in the apical to basal direction. Albumin was segregated from transferrin at the basal surface of the epithelial cells and did not colocalize with either caveolin-1 or -2. Vesicular transport was not disrupted by filipin providing additional evidence that, unlike the vascular endothelium, caveoli are not involved. Cytoplasmic albumin was localized to vesicles containing IgA and transport was disrupted by agents that interfere with clathrin-mediated endocytosis. Together, these findings provide evidence that albumin is transported across the mammary epithelium by the same pathway as immunoglobulin. The possibility that the massive transfer of albumin into mouse milk is mediated by fluid phase transport is considered.     

Structural basis of functional heart failure during the postresuscitation period

Light and electron microscopic study of the myocardium of dogs two weeks after clinical death caused by the loss of blood was carried out and showed that the structural bases of the myocardium contractile function insufficiency during the postresuscitation period included the damage of the contractile apparatus of cardiomyocytes (microlysis and fragmentation of myofibrils, deformation of Z-bands, relaxation of sacromeres) and marked lysis of the sacrotubular system leading to the violation of the excitation-contraction coupling. Cardiomyocyte damages are associated with changes in the microcirculatory channel causing the worsening of transcapillary exchange that provides the tissue homeostasis.     

Fat droplet formation in rat lactating mammary gland and mammary carcinomas viewed by freeze-fracture.

The freeze-fracture morphology of the endoplasmic reticulum and Golgi apparatus membranes was analyzed in lactating rat mammary glands and in mammary carcinomas induced by 7,12-dimethylbenzanthracene or N-nitrosomethylurea. Membranes in close proximity with fat droplets present a spectrum of transformations, from the normal, wavy, particle-rich appearance of cytoplasmic membranes to rigid, particle-free bilayers. The following sequence of events is proposed for the biogenesis of fat droplets: (1) formation of particle-free areas in the endoplasmic reticulum and Golgi membranes; (2) apposition of the bilayered lipid membranes to the growing fat droplet; and (3) progressive conversion of the membrane lipids (or amphypathic lipid precursors) into triglycerides at the periphery of the fat droplet. Our results suggest that membranes are not only involved in the synthesis and secretion processes, but that some of their components are incorporated in the fat droplets and contribute to the secretory product itself.     

Vinblastine-induced microtubular paracrystals in prolactin cells of anterior pituitary gland of lactating rats

Vinblastine sulfate in physiological saline was injected directly into the pituitary glands of lactating rats. Injections were made through the ear canal using a syringe equipped with a 24-gauge needle. The animals were killed at 2, 4, or 6 hours after the injections. When the anterior pituitary glands were examined by electron microscopy, many microtubular paracrystalline deposits were seen in the prolactin and growth hormone cells. The usual cytoplasmic microtubules and microfilaments were not seen in the cytoplasm of these cells. Granular extrusion (exocytosis) was markedly depressed, and an accumulation of secretory granules was definitely observed in the prolactin cells after the administration of vinblastine.     

Volume-activated taurine efflux from the in situ perfused lactating rat mammary gland

The effect of cell swelling on the efflux of amino acids from the in situ perfused lactating rat mammary gland has been examined. Cell swelling, induced by a hyposmotic shock, increased the fractional release of [³H]taurine. In contrast, a hyposmotic shock did not stimulate the efflux of D -[³H]aspartate, suggesting that the effect of a hyposmotic challenge on taurine release cannot be attributed to cell lysis. Volume-activated taurine efflux was reversible, dependent upon the extent of the osmotic challenge and inactivated with a prolonged hyposmotic shock. The release of taurine was also reversibly increased following isosmotic cell swelling (using urea). The results confirm the presence of a volume-sensitive taurine efflux transport system in lactating rat mammary tissue and suggest that the volume-activated amino acid efflux pathway is located at the blood-facing aspect of the mammary epithelium.     

The effects of protein malnutrition on the behavior of rats during the suckling period.

Observations of 2 groups of dams and their litters were made every 3 hr around the clock on Days 1-20 postpartum. The dams fed either an 8% or a 25% casein diet for 5 weeks before mating and during gestation and lactation. Dams on the low protein diet spent more time in the nest actively nursing their young than did high protein dams, and they exhibited no deficits in other maternal behaviors. Five of 11 kinds of behavior developed more slowly in the undernourished pups than in the well-nourished ones, but the developmental delays were no longer than a few days. Circadian fluctuations were apparent in all of the pups' activities during the 3rd postnatal week as well as in grooming and horizontal movement, 2 behaviors that were present earlier, by 6-10 days of age.