Lemen J. Wells

Some Experimental Evidence of Production of Adrenotrophin by the Fetal Hypophysis.

In Conclusion these observations may be taken as experimental evidence of the production of adrenotrophin by the hypophysis of the fetal rat.

Birth Weight and Fetal Mortality in Pregnant Subdiabetic Rats

It has been reported that diabetic women frequently give histories of fetal overweight and of increased fetal mortality in pregnancies occurring many years before the development of manifest diabetes. Wilkerson studied the glucose tolerance in a large series of pregnant women. In those instances where he observed abnormal carbohydrate tolerance during pregnancy, he found that newborns weighing nine pounds or more occurred three times as frequently as in the group with normal carbohydrate tolerance. Lazarow reported that subdiabetes in rats could be produced by injecting subthreshold doses of alloxan. Although these rats had an abnormal tolerance to glucose, their fasting and postprandial blood sugars were normal. They did not show any glycosuria. In two thirds of these animals, subdiabetes persisted for a period up to a year and more. One third of these animals developed manifest diabetes (hyperglycemia and glycosuria) during the first year. The present study was undertaken to determine whether pregnant subdiabetic rats likewise show a high incidence of stillborns and overweight newborns.

COMPENSATORY HYPERTROPHY OF RIGHT ADRENAL AFTER LEFT ADRENALECTOMY: OBSERVATIONS IN FETAL, NEWBORN AND WEEK-OLD RATS.

Summary In our experiments, both ponderal and histologic observations on the adrenal support the view that in the rat the hypophysisadrenal axis begins to function before birth. After birth, there is an hiatus of 3 days during which the function is significantly reduced.

EMBRYOLOGY AND ANATOMY OF THE VAGINA

Carcinoma of the cervix uteri may originate in the epithelium of the vaginal portion of the cervix. Female pseudohermaphroditism is absence of the lower portion of the vagina. The original vaginal epithelium is derived from the fused Mullerian ducts. It is replaced during prenatal life by entoderm from the urogenital sinus and/or by ectoderm from the p roctodeum. The Mullerian ducts develop in human embryos of 37 days ovu lation age. The Wolffian ducts induce the formation of the Mullerian du cts. In the embryo the Mullerian ducts approach each other and fuse in the midline to produce the uterovaginal canal. A solid mass of epitherlium derived from the uterovaginal canal and in part from the urogenital sinus is designated the primitive vaginal plate. The replacement of the origianl vaginal epithelium by the definitive epithelium is finished by the 140 mm stage. The definitive vaginal epithelium is derived from the ectoderm of the cloacal membrane and/or proctodeum. The final vaginal epithelium undermines the Mullerian epithelium which disappears. When androgen is introduced into the circulation of a female fetus induced abnormalities include absence of the lower part of the vagina. This involves the abnormal persistence of the urogenital sinus. The growth of the human vagina during prenatal life reflects the action of the hormones of pregnancy. The sharp dip in the growth curve during early postnatal life reflects the lack of these hormones. The relatively large size of the vagina at term is correlated with the descent of the bladder.

Response of Beta Cells to Different Levels of Glucose: Fetal Pancreases Grown in Organ Culture and Subsequently Transplanted to Maternal Hosts

Portions of pancreases from fetal rats (normal or alloxan diabetic mothers) of 19.5 days were grown in organ culture for four days on either a low glucose medium (162 to 170 mg. glucose per 100 ml.) or a high glucose medium (1,031 to 1,073 mg. glucose per 100 ml.). Certain cultures were fixed for microscopic study. Other cultures were transplanted to the mothers at two sites: into the anterior chamber of the eye and under the capsule of the kidney. Four or ten days later, the grafts were removed, fixed and prepared for microscopic study. Pancreases of fetuses from normal mothers had granulated beta cells at the time of explantation. When explants were grown on the high glucose medium, the beta cells became degranulated—the insulin stored at the time of explant was released from the beta cells. Subsequent transplantation of such cultures into the normal mothers restored the beta cell granulation, i.e., new insulin was synthesized and stored within the beta cells. Pancreases of fetuses from alloxanized diabetic mothers had de granulated beta cells at the time of explantation. When these explants were grown on the low glucose medium, the beta cells developed extensive granulation representing a synthesis and storage of insulin. Following subsequent transplantation of such cultures into the diabetic mothers, the beta cells became degranulated, i.e., release of stored insulin from the beta cells. These observations indicate that the beta cells maintain their functional integrity (ability to store or release insulin in response to glucose) both in organ culture and when subsequently grown as grafts in maternal hosts.

Response of the hypothalamic-hypophyseal adrenal axis to stress: observations in fetal and caesarean newborn rats.

Summary A fetal rat given epinephrine showed a depletion of the ascorbic acid in the adrenals, but a decapitated fetus did not, nor did an intact (nondecapitated) fetus given saline instead of epinephrine. In a premature newborn obtained by Caesarean section (detached from placenta or not detached), injection of epinephrine did not cause a depletion of the ascorbic acid. These observations support the views that in the rat the hypothalamic-hypophyseal adrenal axis begins to function before birth and that after delivery this axis temporarily becomes refractory to stimulation by injected epinephrine.

Insulin Content of Fetal Rat Pancreases Grown in Organ Culture and Subsequently Transplanted into Maternal Hosts

Portions of pancreases from 19.5-day fetal rats were grown in organ culture on two types of liquid media: low glucose, containing 162 to 170 mg. glucose/100 ml.; high glucose, containing 1,031 to 1,073 mg. glucose/100 ml. Following four days of organ culture, the tissues were extracted and assayed for insulin content (immunoassay). Other cultures were transplanted to maternal hosts at two sites: beneath the capsule of the kidney and into the anterior chamber of the eye. Ten days later, the transplants were removed and assayed for insulin content. Large quantities of immunologically active insulin were present in the culture media following forty-eight and ninety-six hours of incubation. Expiants exhibited a four- to sixfold increase in insulin content following four days in vitro. Pancreatic expiants cultured on the high glucose medium contained less extractable insulin than similar ex-plants cultured on the low glucose medium. When cultured expiants were transplanted to hosts with normal blood glucose levels, the total extractable insulin content of the grafts was 55 per cent to 130 per cent greater than that at the time of transplantation. When cultures were transplanted to alloxan diabetic hosts, the total extractable insulin content of the grafts was less than that found in grafts to normal hosts. A small but statistically significant drop in blood glucose level was observed in hyperglycemie diabetic maternal hosts receiving transplants of organ cultured pancreas. These results indicate the continued growth and functional responsiveness of the islet beta cells during organ culture and following subsequent transplantation.

Experimental Evidence of the Secretion of Urine by the Fetal Kidney.

Summary The bladders of fetal rats were allowed to fill after the urogenital papilla had been ligated. The contents of the bladder and the blood of the fetus were analyzed, as were also those of the mother. The observations indicate that the fetal kidney produces urine which is somewhat dilute.

Effects of Different Levels of Glucose upon the Development of Granulated Beta Cells in Cultures of Pancreatic Primordia from Normal Rat Embryos

Pancreatic primordia from normal rat embryos of 14.5 to 15.5 days postcoitum were grown in organ culture on liquid media with 173, 350, 526 and 995 nig. of glucose per 100 ml. The periods of culture were as follows: eight days (14.5 day embryos) and six days (15.5 day embryos). In cultures grown on the standard medium with 173 mg. of glucose per 100 nil., the pancreatic islets had many granulated beta cells. In cultures grown on high-glucose media with 350, 526 and 995 mg. of glucose per 100 nil. the islets had fewer granulated beta cells. These observations are interpreted to mean that highglucose levels in the media inhibit the production of granulated beta cells in the islets of the cultures.

Development of the pancreas of the mouse embryo in vitro: Acini and islets

Abstract Developing pancreata from mouse embryos of 11 1 2 to 18 1 2 days were explanted onto a clotted medium of cock plasma and chick-embryo extract and cultivated at 37°C for periods of 1 to 9 days. The cultures usually were fixed and sectioned and the sets of serial sections stained. Cultures from embryos as young as 12 1 2 days gave rise to pancreatic acini and to islets without blood vessels. Cultures from embryos as young as 13 1 2 days yielded acini with zymogen granules of a stage as advanced as that in a normal embryo of 17 1 2 days. When the explants were from embryos old enough to have primitive islets of Langerhans, 13 1 2 days or older, any continued development of islets in vitro largely involved an increase in the size of islets and islet cells (versus increase in number of islets). Techniques which served to demonstrate β-granules in the islet cells of the intact pancreas failed to do so in the cultured pancreas.