MATERNAL AND FETAL FACTORS AFFECTING THE GROWTH AND FUNCTION OF THE RAT PLACENTA

ABSTRACT Interrelations among maternal, fetal and placental endocrine systems have received little attention in the extensive studies thus far conducted on placental endocrine function. Yet, increasing indirect evidence suggests that maternal and fetal endocrine glands affect the growth and endocrine function of the placenta. The present research was designed to investigate these interactions following the pattern of classical endocrinological experiment in which the placenta would represent the "target" gland and the maternal and fetal glands, the "tropic" glands. The maternal glands were represented by the ovaries and the adrenals, whereas the fetal glands, for practical purposes, were considered as a whole, i.e. as a present or absent fetus. All "endocrinectomies" (ovariectomy, adrenalectomy and fetectomy) were performed alone and in combination in pregnant Long - Evans rats on day 13 of gestation, and in each case the placenta was left in situ, undisturbed. Animals were divided into eight groups (4 animals in each group and for each placental age studied) as follows: normal; fetectomized (F); ovariectomized (Ō); adrenalectomized (A); fetectomized and ovariectomized (FO); fetectomized and adrenalectomized (F̄Ā); ovariectomized and adrenalectomized (ŌĀ); fetectomized, ovariectomized and adrenalectomized (F̄ŌĀ). Placentae were subsequently removed on days 15, 17, 19 and 21 of "gestation" and their growth and metabolic activity was assessed in terms of wet weight, total protein, DNA and RNA content, 3H-Leucine incorporation rate into proteins, and 59Fe-labelled blood uptake, as well as by histological techniques. Statistical analyses consisted of (1) a factorial design analysis to reveal interactions among the various factors, and (2) a t- test analysis of the differences among the simple factorial effects. Because of the similarity of placental response to F̄ and F̄Ā, Ō and OA, and FO and FOA, the following discussion is limited to groups F, Ō, F̄Ō and Ā. The histological, biochemical and functional evidence indicates that fetectomy destroys the nonendocrine elements of the rat placenta, but that the structural integrity and metabolic activity of the endocrine elements are maintained throughout "gestation". The giant and small cytotrophoblastic cells and the labyrinthine syncytiotrophoblast—elements implicated by others in the production of placental hormones—were found histologically to be sound, whereas the fetal mesenchyme and endothelium, the trophoblastic cells of the trilaminar structure connected with the fetal vessels, and the glycogen cells were found to be degenerated. The decrease observed in placental weight, total protein and RNA content throughout pregnancy, as well as the initial decrease in total DNA content are attributed to the destruction of the nonendocrine placental elements. On the other hand, the finding that placental weight, although lower than normal, remained constant throughout term, together with the findings that 3H-Leucine incorporation rate was similar to normal and total DNA content returned to control values by day 21, further indicate that some placental elements remain viable following fetectomy. Since neither 59Fe-labelled blood uptake, nor histological evidence revealed significant differences between fetectomized and control animals in the amount of maternal blood in the placenta, the biochemical changes noted above do not reflect changes in the blood content of the placentae. Ovariectomy invariably led to fetal death within 5 to 6 days. This fact was reflected in the response of all the placental parameters studied, initially displaying values similar to normal and subsequently resembling those recorded in F̄ placentae. These findings confirm the assertion by other investigators that although the ovary is essential for the maintenance of pregnancy in the rat, the functional and morphological integrity of the endocrine placental elements is not influenced by ovariectomy. The placental findings recorded in the F̄Ō group revealed a significant interaction between F̄ and Ō. Unlike F̄ and Ō animals, in F̄Ō animals placental weight, total protein, DNA and RNA content were similar to normal; 3H - Leucine incorporation rate was two to three times higher in F̄Ō and F̄ŌĀ animals than in controls. Histological examination indicated that the elements responsible for these findings were the giant cells, which increased in number and size, and the small cytotrophoblastic cells, which also proliferated; the labyrinth displayed the same picture as in F̄ animals and the amount of blood present in the placenta did not increase after F̄Ō, thus being irrelevant to the biochemical findings. It is evident that F̄ and Ō when combined, significantly stimulated the metabolic activity of the placenta. Thus the endocrine elements of the rat placenta appear to be subject of a dual inhibitory influence emanating from both the fetus and the ovary; accordingly, their removal, by eliminating the inhibitory action of fetal and ovarian factors on placental growth, leads to placental hypertrophy, whereas elimination of either one of these factors alone is not sufficient to elicit this placental response. Adrenalectomy did not affect the maintenance of pregnancy; however placental weight and total DNA and RNA content were lower than normal on day 15 of gestation whereas on day 19 total protein content was lower and 3H-Leucine incorporation rate was higher than normal. No histological changes or differences in 59Fe-labelled blood uptake were observed between placentae from Ā and normal rats. To account for these noxious effects, one might speculate that adrenalectomy disturbs the progestational and estrogenic equilibrium necessary to normal placental function. In summary, fetectomy, ovariectomy and adrenalectomy performed as single operations interfere with the growth and metabolism of the placenta but, in general, do not affect its endocrine elements. When fetectomy and ovariectomy are combined, however, these endocrine elements are released from ovarian and fetal inhibitions and proliferate, thus leading to an increase in placental weight and to biochemical changes that are generally similar to the normal changes occurring throughhout the course of gestation in the rat.