The Correlation Between the Cyclic Changes in the Uterus and the Ovaries in the Guinea-Pig

The cyclic changes in the epithelial as well as connective tissue structures of the uterus during heat preceding copulation and the changes following copulation are described; the influence of polynuclear leucocytes in these changes is shown. The latter are present during the first two days following copulation. The decidual cells originate from the connective tissue cells of the mucosa. Various periods of the sexual cycle are characterized through the shape and mitotic proliferation of various epithelial and of the connective tissue cells. From the sixth to the twelfth day after ovulation mitoses are usually absent in the epithelial structures; afterwards they begin to reappear, from the eighth day on to the end of the sexual cycle mitoses are absent in the connective tissue. 2. As long as the corpora lutea functionate, the presence of mature follicles in the ovaries does not produce those changes in the uterine mucosa which are characteristic of the period of heat. 3. During pregnancy the structure of the uterus is that of a resting organ, in which epithelial as well as connective tissue cells are small and the latter are without mitotic proliferation. 4. In animals in which heat has been observed without copulation taking place, the cyclic changes in the uterus are approximately the same as in animals in which copulation did take place, in which however pregnancy had been prevented through an early ligature of the fallopian tubes. The main difference in these two series is caused through the very marked migration of polynuclear leucocytes through the mucosa in cases in which copulation took place. 5. Ovulation is usually accompanied or directly followed by certain changes in the uterine mucosa. These changes permit us in many cases to decide whether or not in an animal in the period of heat ovulation has or has not yet taken place. 6. Extirpation of almost the whole uterus or thyroids does not prevent the occurrence of heat in the operated animals. 7. In animals which were prevented from copulating or in which the fallopian tubes were ligated soon after copulation, the period of heat occurs approximately every fifteen to nineteen days. 8. The proportion of ovarian follicles which are in the late stages of connective tissue atresia to well preserved follicles and follicles in the stage of granulosa degeneration shows two maxima, one about six to seven days after ovulation and another at the time preceding the next ovulation. Under certain conditions, however, the number of quite atretic follicles may be small at the time of heat, namely in young guinea-pigs which are in heat for the first time, and it may be relatively large at other periods of the sexual cycle in old guinea-pigs. 9. As we showed previously an early extirpation of the corpora lutea leads in the large majority of cases to an acceleration of the next ovulation. Certain conditions, however, may prevent the early ovulation. In the latter cases the structure of the uterus corresponds to the late stage of the sexual cycle. If however a new premature ovulation is brought about through the extirpation of the corpora lutea, a new cycle starts in the uterus at the time of the accelerated ovulation. Mature follicles, or possibly other follicles, are in the absence of corpora lutea able to call forth the structural changes in the uterus accompanying heat and the rupture of the follicles and development of corpora lutea is followed by the typical uterine cyclic changes. 10. We stated previously that also during pregnancy extirpation of the corpora lutea is followed by an early ovulation. While thus pregnancy in itself does not prevent an ovulation to take place (only the corpora lutea persisting during pregnancy preventing the ovulation) pregnancy does prevent the cyclic changes of the uterus preceding, accompanying or following ovulation; during pregnancy the uterus retains its resting condition notwithstanding ovulation. This influence of pregnancy is not a mechanical one, inasmuch as it is found in the non-pregnant horn as well as in the pregnant horn in cases in which a pregnancy developed only in one horn. The presence of a necrotic placentoma or the occurrence of an abortion does not prevent the cyclic changes in the uterus that set in with ovulation. 11. If five to seven days after copulation both horns of the uterus are split lengthwise and the development of a normal pregnancy is prevented, ovulation is delayed under those conditions; it occurs between the twentieth and thirtieth day after the previous copulation, even in cases in which a developing embryo could not be seen in the placentomata growing at the site of the incisions. On the other hand in a case of an experimentally produced extrauterine pregnancy degeneration of the corpus luteum and a new ovulation were not delayed notwithstanding the presence of living embryonic (including placental structures of embryonic origin) in the animal. These observations suggest that it is primarily the life of the maternal part of the placenta which prevents the new ovulation during pregnancy and that the embryonic structures are only indirectly concerned in this effect. We are testing this suggestion still further at the present time. 12. A description of the signs of heat is given in accordance with the observations of the breeder, Miss A. E. C. Lathrop. 13. After total extirpation of the ovaries, the uterine mucosa becomes similar to the mucosa of the pregnant uterus in a non-pregnant horn; gradually an atrophy of the different layers of the uterine wall takes place. If we extirpate the ovaries soon after ovulation the effect is the same as if the corpora lutea are extirpated at that period, as far as the predecidual proliferation in the connective tissue and the accompanying changes in the epithelium which take place between the fourth and seventh day are concerned. As far as this effect is concerned the corpus luteum is the active part of the ovaries. While, however, extirpation of the corpora lutea does not prevent those uterine changes which accompany heat and does not prevent a new sexual cycle, extirpation of the ovaries prevents all cyclic changes in the uterus. 14. Early extirpation of the corpora lutea within the first forty hours after copulation prevents in a similar manner the development of experimental placentomata as an early extirpation of the ovaries. If the ovaries are removed six to eight days after copulation and at the same time incisions are made into the uterus, either none, or only very small placentomata develop and the developing placentomata die at an earlier date than they would have done otherwise. An extirpation of the corpora lutea six to seven days after copulation also causes the developing placentomata to be smaller. If under these conditions an ovum develops in the incised uterus within the decidual tissue, the development of the ovum is usually much retarded. A similar retardation of the development of the ovum we observed in a case of experimentally produced extrauterine pregnancy in the guinea-pig. If the ovaries are extirpated two days after the making of the incisions the developing placentomata are usually smaller. Castration done at a time when the placentomata had already reached a considerable size causes an acceleration in the necrosis of the placentomata. Castration does however not prevent regenerative changes in the uterine mucosa. 15. The existence of pregnancy in one horn of the uterus prolongs markedly the life of placentomata produced in the other horn. 16. For certain phases of the cyclic changes of the uterus the presence, for other phases the absence, of a functionating corpus luteum is necessary; but certain other ovarian structures (probably mature follicles and not the so-called interstitial gland) are required for the latter phases. In addition the absence of pregnancy (and probably of living placentomata) is a condition for the typical course of the cyclic changes in the uterine mucosa.