According to a proposal by Shelesnyak (1957, 1960), histamine is the chemical stimulus which causes deciduoma formation. Subsequent studies have also indicated that histamine is involved in the decidual reaction (cf. Marcus, Kraicer & Shelesnyak, 1963; Kracier, Marcus & Shelesnyak, 1963). A student laboratory manual, in an experiment to demonstrate the formation of deciduomata, specifies the use of histamine (Zarrow, 1960). However, in our experience histamine does not produce deciduomata in rats made pseudopregnant by sterile matings. Also, Finn & Keen (1962), using rats made pseudopregnant by electrical stimulation of the cervix, were unable to cause decidual reactions with histamine injections. Orsini (1963) was unable to produce decidual reactions in either the rat or the hamster with systemic injections of pyrathiazine, a histamine-releasing agent. Further, Banik, Kobayashi & Ketchel (1963) have shown that increasing or decreasing the histamine
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UPENDRA K. BANIK and MELVIN M. KETCHEL
SERGE J. MANTALENAKIS and MELVIN M. KETCHEL
Rats and mice ovulate and are receptive to males on the 1st or 2nd night following parturition. An animal may thus be pregnant while it is lactating, but implantation is often delayed (Lataste, 1891). In general, it appears that the length of the delay in implantation is correlated with the number of suckling young (Enzmann, Saphir & Pincus, 1932).
The data concerning delayed implantation in lactating rats and mice have been collected from relatively small numbers of experimental animals. The Charles River Breeding Laboratories, a commercial producer of rats and mice for scientific research, have made available to us breeding records of a larger population from which it is possible to estimate the frequency of delayed implantation and the length of the delay.
One pair of Charles River CD* rats (derived from Sprague-Dawley) or Charles
SERGE J. MANTALENAKIS and MELVIN M. KETCHEL
Although considerable information is accumulating concerning the endocrinology of parturition, the nature of the underlying stimulus controlling the onset of parturition remains obscure (for review see Marshall & Moir, 1952; Zarrow, 1961). The present study was undertaken to determine whether or not parabiosis would reveal the existence of a humoral factor which controls the onset of parturition. Earlier studies by Sauerbruch & Heyde (1910), Fels (1929) and Hill (1932) demonstrated that parturition is unaffected in a pregnant rat joined in parabiosis with a non-pregnant rat. Kross (1926) and Munemitsu & Segal (1959) reported no evidence of a disturbance in length of gestation or in parturition when two pregnant rats were placed in parabiosis. We reasoned that a humoral factor released as a stimulus to parturition in the rat might not cause the onset of parturition in its parabiotic
MELVIN M. KETCHEL, UPENDRA K. BANIK and SERGE J. MANTALENAKIS
Summary.
Parabiosis of rats on Day 1 of pregnancy with Day-1 pregnant females, non-pregnant females or male rats resulted in delayed implantation of ova. The delayed implantation was not caused by the surgery involved nor by the stress of restricted movement, for when surgery was performed without parabiosis, or when rats were sutured together without parabiosis, pregnancy proceeded normally. Delayed implantation did not occur when parabiosis was of the skin to skin type, but did occur when skin and muscles were joined. Parabiosis on Day 1 or Day 3 caused delayed implantation, but parabiosis on Day 5 did not. Parabiosis on Day 1 which was terminated after 24 hr did not result in delayed implantation, but 72 hr of parabiosis did. Experiments on adrenalectomized rats suggest that adrenal secretions are not involved. The decidual reaction of rats in parabiosis was inhibited. Ova recovered from rats in parabiosis were delayed in development, but some implanted normally when transferred to normal pseudopregnant recipients. Treatment of parabiotic rats with 0·1 μg of oestradiol on Day 4 of pregnancy resulted in normal implantation in some individuals.
UPENDRA K. BANIK, YUTAKA KOBAYASHI and MELVIN M. KETCHEL
It has been suggested by Shelesnyak (1957) that histamine might be the chemical stimulus responsible for the implantation of blastocysts. According to Shelesnyak's hypothesis (1960), an oestrogen surge results in the liberation of histamine, and the released histamine induces stromal cells of the endometrium to transform into decidual cells. Much of the experimental work supporting this hypothesis rests on the observation that, in rats, local application of antihistamine agents to the uterus suppresses the decidual transformation and inhibits the normal implantation of blastocysts.
The possibility remains, however, that the effects of the antihistamines described by Shelesnyak may be non-specific, and interfere with implantation in some manner not involving histamine. The experiments described in the present report were undertaken in an attempt to extend the evidence concerning the possible role of histamine in the process of implantation.
