Delayed nidation in the rat induced by autografts of the hypophysis with a case report of "asynchronous implantation".
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Objective of this study was to determine the ability of a delayed-implantation-associated protein (MW 170,000, DIAP170K) to inhibit DNA synthesis by mouse blastocysts. Mice were ovariectomized on day 3 of pregnancy and treated with daily injections with 1 mg progesterone till day 7 to induce delayed implantation. Blastocysts were collected on day 8 with or without a single injection of 25 ng estradiol-17 beta on day 7 that activates blastocyst metabolisms (activated blastocysts and delayed-implanting blastocysts respectively). DNA synthesis was determined by measuring [3H]thymidine incorporation by blastocysts. DIAP170K at 10 micrograms/m/ suppressed resumption of DNA synthesis by delayed-implanting blastocysts and suppression was maximal at 50 micrograms/m/. However, DIAP170K did not affect DNA synthesis by blastocysts obtained on day 5 of pregnancy (normal blastocysts) and activated blastocysts. Resumption of DNA synthesis in the inner cell mass (ICM) and trophectoderm from delayed-implanting blastocysts was then separately assessed. DNA synthesis resumed in the trophectoderm of intact blastocysts during 24-hr culture but not in the trophectoderm cultured apart from the ICM. DIAP170K inhibited the resumption of DNA synthesis by the trophectoderm of intact delayed-implanting blastocysts but did not affect DNA synthesis by the ICM. In conclusion, DIAP170K inhibits resumption of DNA synthesis by trophectoderm of delayed-implanting blastocysts. This action of DIAP170K may play a central role in maintaining, but not achieving, dormancy of DNA synthesis by delayed-implanting blastocysts in mice.
In Schreibers' long-fingered bat (Miniopterus schreibersii) from South Africa, implantation is delayed from May to August during which time the corpus luteum is inactive and plasma progesterone and LH concentrations low. Treatment of pregnant long-fingered bats with exogenous prolactin for 10 days in early delayed implantation (May) resulted in changes in luteal ultrastructure that were consistent with increased steroidogenesis, high plasma progesterone concentrations and the initiation of implantation. Treatment of bats with hCG for 10 days in early delayed implantation induced similar changes in luteal ultrastructure and plasma progesterone concentrations, but did not initiate implantation. Treatment with exogenous progesterone during early delayed implantation had no influence on the corpus luteum or the conceptus. We conclude that prolactin is the most important pituitary hormone in the control of delayed implantation, although the route via which it induces implantation is unknown.
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Progesterone and oestrogen are required for implantation in the mouse and rat. In both animals prolactin and LH stimulate ovarian progesterone production oestrogen is stimulated by FSH in the mouse but both LH and FSH appear to be required in the rat. There is no evidence that preimplantation embryonic gonadotrophins, if they exist in these species, are involved in the initiation of implantation. The delay of implantation in suckling mice and rats is due to a lack of oestrogenic stimulus. This is caused by an inhibition of FSH release from the pituitary gland. The inhibition of FSH release appears to be caused by lack of a competent hypothalamic releasing factor. High circulating levels of prolactin and/or LH and/or progesterone do not seem to be responsible for the FSH inhibition during suckling-induced delayed implantation. Increased or decreased prolactin release does not affect FSH release during early pregnancy in the mouse.
Catechol estradiol can induce implantation of the embryo in a progesterone-primed uterus, but we do not know whether conversion of estrogen to a catechol is essential for implantation. The present study examined the ability of fluorinated estradiols that have a reduced capability of catechol formation to induce implantation. Delayed implantation in rats that were hypophysectomized on the third day postcoitum was maintained by daily injection of progesterone. On the fifth day of progesterone treatment they were injected intravenously with estradiol-17 beta (E2), or various doses of 2-fluoroestradiol-17 beta (2-F1-E2) or 4-fluoroestradiol-17 beta (4-F1-E2) and examined 24 hr later for evidence of initiation of implantation. All animals treated with 25 ng of E2 showed normal numbers of implantation sites, as did those receiving 60 ng of 4-F1-E2. In contrast, 2-F1-E2 failed to initiate implantation with doses as high as 300 ng per animal; there were only single sites in two of eight rats treated with 500 ng. Initiation of implantation was not correlated with lack of uterotropic estrogenicity. The results suggest that formation of catechol estrogen may be an important step in mediating estrogen function for implantation of the embryo.
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Pregnant mice were ovariectomized 3 days after mating and pregnancy was maintained by progesterone treatment. Different regimens of intraperitoneal injections of 3'-deoxyadenosine were applied 3 days after ovariectomy. Repetition of the injections at 3 h intervals induced a significant rate of implantation by delayed blastocysts. Other types of treatment with 3-deoxyadenosine as well as adenosine injections were found to be ineffective. Paradoxically, 3'-deoxyadenosine treatment had an adverse effect on the overall pregnancy rate found at autopsy.
In Schreibers' long-fingered bat from South Africa (approximately 33 degrees S) copulation, ovulation and fertilization occurred in April and May, implantation was delayed until August, and parturition occurred in December. Delayed implantation coincided with winter, during which the bats remained active, only entering prolonged periods of torpor during particularly cold spells. Plasma progesterone concentration was low during non-pregnancy (1.54 ng/ml) and during delayed implantation (1.67 ng/ml), and thereafter increased to reach a peak mean of 64.82 ng/ml in late pregnancy. Changes in size and ultrastructure of the luteal cells indicated periods of steroidogenesis just after formation of the corpus luteum, and for about 2 months after implantation; reduced steroidogenic activity during delayed implantation; and luteolysis in the last 2 months of pregnancy. Plasma luteinizing hormone (LH) concentration and pituitary LH-beta immunoreactivity were highest during follicular development and peaked just before ovulation. During early delayed implantation, plasma LH concentration was low, and both plasma LH and pituitary LH-beta immunoreactivity increased from July, reaching peaks in late pregnancy. LH may be required to activate the corpus luteum and terminate delayed implantation, or, as in some small carnivores, it may be required for luteal maintenance.
It has been hypothesized that it is rat placental lactogen (rPL) which causes PRL surges to terminate at mid-pregnancy. Using a hormonally induced model of delayed implantation, the temporal relationship between the secretion of rPL and the nocturnal PRL surges was followed. Implantation was prevented by removing the ovaries, the source of estrogen, on day 3 of pregnancy. Blastocysts were maintained free-floating in the uterine lumen by sc injection of 4 mg progesterone in oil daily for 0, 5, 7, or 9 days. Implantation was induced and the subsequent pregnancy was maintained with 1 microgram estrone plus 4 mg progesterone daily. Nocturnal PRL surges (0500 h) were followed for 10 days after the first estrone injection. Control animals last exhibited PRL surges on day 10. Animals with 5, 7, or 9 days of implantation delay had their last PRL surge on days 15, 17, and 18, respectively. Levels of rPL in control animals, as measured by Nb2 lymphoma cell bioassay, were low on day 6, slightly higher on day 10, and significantly elevated on day 12. Delaying implantation delayed the increase in rPL secretion in the experimental groups. This proportionately prolonged the number of days the PRL surges were present. These data suggest that the termination of the nocturnal PRL surges requires the secretion of rPL by the developing conceptus.
In several carnivores a newly fertilized egg enters diapause instead of being directly implanted into the uterus, a phenomenon called delayed implantation. Several hypotheses have been forwarded to explain the utility of this prolonged gestation period, but all of these depend on several independent origins of the character. Here, we conduct a phylogenetic reconstruction of the evolution of delayed implantation in the Carnivora that reveals one basal origin, with additional transitions all having occurred within the Mustelidae. Hence, previous hypotheses relating to its evolution become untestable. Further analyses revealed that the presence or absence of delayed implantation is unrelated to the timing of mating season and birth season. Instead, mustelids with direct implantation are smaller than those with delayed implantation. We therefore suggest that delayed implantation has been selected against in small species due to the relatively higher fecundity costs of a prolonged gestation period.
Reactivation of the corpus luteum, resumption of embryonic development and ovoimplantation can be obtained experimentally and precociously with corrected manipulation of light and temperature.
Androstenedione and testosterone were measured by radioimmunoassay after chromatography on celite microcolumns throughout the delayed implantation period in the European badger (Meles meles L.). Androstenedione and testosterone concentrations varied from 0.05 to 22 ng/ml, and from 30 pg/ml to 359 pg/ml, respectively. There was a typical biphasic pattern in the fluctuation of these two steroids. Androstenedione levels increased between June and August (X= 7.9 +/- 0.8 ng/ml), decreased from September to November (X = 2.3 +/- 0.3 ng/ml), and then increased again from December to February (X = 6.1 +/- 0.7 ng/ml). The same fluctuations of the testosterone levels were observed throughout the diapause, but the concentrations were lower. The overall correlation between androstenedione and testosterone was highly significant (r = 0.75, P less than 0.001). There was also a similarity between the androgen and progesterone patterns of secretion (r = 0.31), particularly at the end of the delay period (r = 0.73, P less than 0.001). No correlation could be demonstrated between androgens and estrogens.
Luteal function in Pine Marten (Martes foina), species which exhibit delayed implantation, shows low progesterone plasma levels during the major part of diapause. A significant increase occurs before implantation. These results confirm histological appearance observed in lutea corpora.
Despite the high cost of lactation alone, concurrent pregnancy and lactation (CPL) is widespread among rodents. Many species that exhibit CPL delay implantation of the litter in utero while nursing. The first purpose of this study was to describe the pattern of energy allocation during CPL in a species with a large degree of overlap between gestation and lactation. Resting metabolic rate, food consumption and mass changes of Norway rat dams and litters, digestive efficiency and urinary energy loss of dams, and pup tissue energy equivalents were determined for CPL dams and for dams that were only lactating (C). CPL dams had significantly higher metabolic rates than C dams. Food consumption, pup growth, tissue energy equivalents, and assimilation efficiency were similar for both groups. The energy equivalent of mass change was greater for C dams, which gained in maternal mass (lipid) during lactation, than for CPL dams, which only increased in mass because of the litter in utero. The second purpose of this study was to investigate the suggestion that delayed implantation during CPL evolved as a mechanism to lower peak energy demands during CPL. Concurrently pregnant and lactating dams were injected with estrone (ECPL dams) on days 3-16 of lactation to prevent them from delaying implantation. A group of dams that were only lactating also received estrone injections (EC dams). ECPL dams produced smaller offspring at weaning than EC dams.(ABSTRACT TRUNCATED AT 250 WORDS)
Mouse blastocysts in delay of implantation and after an 18-hour activation for implantation by estrogen were recovered by flushing with glutaraldehyde containing Alcian Blue or by flushing with cold Dulbecco's PBS containing 0.1% sodium azide for further processing according to an Alcian Blue technique and a ConA-latex technique, respectively. Blastocysts in delay of implantation showed no or only faint staining with Alcian Blue, while blastocysts activated for 18 hours displayed a marked staining of the abembryonic pole. Binding of ConA-latex spheres demonstrated a markedly higher density at the abembryonic end of both delayed and implanting blastocysts. It is concluded that, as demonstrated by the Alcian Blue technique, the abembryonic trophoblast, which is the first one to attach and invade at implantation, has changed the properties of the extracellular coat, probably in a way that favors increase of adhesiveness and invasiveness. The similarity in pattern of ConA binding of both delayed and implanting blastocysts, however, suggests that this property is related more to preimplantational differences in proliferative activity of the two poles than to implantatory changes.