Distribution of hyaluronan in the mouse endometrium during the periimplantation period of pregnancy

The tissue distribution of stromal hyaluronan (HA) in the periimplantation mouse uterus was studied histochemically using a biotin-labelled HA-binding complex from cartilage proteoglycan. HA is present around proliferating stromal cells in both the pregnant and pseudopregnant mouse uterus prior to their differentiation into the decidualized phenotype. Decidualization is accompanied by clearance of HA from the extracellular matrix (ECM). This clearing is part of an intrinsic developmental program of the differentiating deciduum. A specific embryonic signal from the implanting conceptus is not required for this phenomenon to occur, since a similar response could be induced in deciduoma produced by artificial stimulation of a receptive uterus. Clearing of HA from the antimesometrial stroma is consistent with the hypothesis that the HA-negative decidual cell may be involved in restricting the invasion of trophoblast cells during embryo implantation. Retention of HA within angiogenic regions of the decidua basalis implies a functional role for this molecule in placental vascularization.     

Spatiotemporal expression of cyclooxygenase 1 and cyclooxygenase 2 during delayed implantation and the periimplantation period in the Western spotted skunk

Embryonic development in the western spotted skunk is arrested after blastocyst formation for about 200 days. This developmental arrest is believed to be due to insufficiency of uterine conditions to support continuous development. Implantation and decidualization are defective in cyclooxygenase 2 (Cox2)-, but not Cox1-, deficient mice. We therefore used Northern and in situ hybridization to investigate changes in uterine expression of Cox1 and Cox2 genes during various stages of pregnancy in the spotted skunk. Cox1 was constitutively expressed at all stages of pregnancy examined, but it did exhibit localized up-regulation in the trophoblast and necks of uterine glands at early implantation sites. Cox2 expression was highly regulated with little or no expression during delayed implantation. Cox2 expression was first detected in the uterus and trophoblast prior to blastocyst attachment and remained detectable for 5-6 days after blastocyst attachment. Cox2 expression was also localized in the luminal and glandular epithelia of uterine segments located between implantation chambers. Changes in Cox expression were not correlated with the abrupt increase in uterine weight that occurs simultaneously with renewed embryonic development but was correlated with an influx of serum proteins into the uterus observed in a previous study.     

Catecholoestrogen synthesis and metabolism in the rabbit uterus during the periimplantation period

Microsomal oestradiol-2/4-hydroxylase (OE-2/4-H) and cytosolic catechol-O-methyltransferase (COMT) (EC 2.1.1.6) activity in the uteri of pregnant and pseudopregnant rabbits during the periimplantation period were studied. The apparent Km for the 4-hydroxylation of oestradiol (3.18 microM) was considerably less than for the 2-hydroxylation reaction (13.36 microM), whereas the Vmax were almost equal. This suggests that 4-hydroxyoestradiol (4-OH-OE2) is the predominant product of OE-2/4-H in the rabbit uterus. These reactions were inhibited by SKF-525A, indicating the involvement of cytochrome P450 dependent monooxygenases. Uterine cytosolic COMT utilized 2-hydroxyestradiol (2-OH-OE2) as the preferred substrate as compared to 4-hydroxyoestradiol (4-OH-OE2). Since the rabbit uterus has a considerable capacity to synthesize 4-OH-OE2 and a lower capacity to metabolize it, it could be suggested that more 4-OH-OE2 than 2-OH-OE2 could be available to the uterus for its physiological activities. Furthermore, an increase in OE-2/4-H in Day 6 pseudopregnant and pregnant uteri with a concomitant decrease in COMT suggests the involvement of catecholoestrogens in the implantation process in the rabbit.     

Production of leukotrienes and prostaglandins in the rat uterus during periimplantation period

We have measured by radioimmunoassay the production of leukotrienes (LTC₄ and LTB₄) and prostaglandins (PGE₂ and PGF_2α) in the rat uterus on Days 1 through 6 of pregnancy. The production is defined as the synthesis minus the degradation for a defined period. The production of LTC₄ or LTB₄ remained unaltered on days 1–3, but exhibited a marked increase on Day 4 showing a peak at noon. This was then followed by a sharp decline on Day-5 morning. A small but consistent peak in uterine LT production was also noticed on Day-5 noon prior to implantation and this was followed by a decline on Day-6 morning i.e. after initiation of implantation. The production profile of PGE₂ and PGE_2α showed a striking resemblance to that of LTs; one exception being that maximal PG production was noticed on Day-4 morning and preceded the peak production of LTs. These vasoactive arachidonate derivatives reached their peak production rates at around the time when a surge in estrogen level is noticed in the uterus on Day 4. Implantation is a local proinflammatory type of reaction that is associated with increased uterine vascular permeability. Vascular changes in inflammatory reactions are provoked by two kinds of chemical mediators: (1) vasodilators and (2) agents that increase vascular permeability. PGs (especially of the E series) are known as vasodilators, while LTs and histamine mediate increases in vascular permeability. Therefore, an interaction between LTs, PGs, and histamine could be important for uterine preparation for implantation and/or implantation .     

Critical progesterone requirement for maintenance of pregnancy in ovariectomized rats

The minimum progesterone concentration required to maintain the pregnancy was studied by varying doses of progesterone given subcutaneously to rats ovariectomized on Day 8 of pregnancy. Injecting 3 mg progesterone plus 200 ng oestradiol benzoate daily provided serum progesterone values between 25.4 +/- 7.0 and 35.2 +/- 6.2 ng/ml throughout Days 10-19 which were significantly lower than normal levels (P less than 0.05), but resulted in 93.6% of fetal survival on Day 19 which was not significantly different from 93.3% in the control group. Injecting 2 mg progesterone plus 200 ng oestradiol benzoate daily gave progesterone values between 13.2 +/- 4.6 and 19.0 +/- 6.2 ng/ml and could not maintain fetal viability to Day 19 (14.2%, P less than 0.05 compared with control group). Critical times to supplement progesterone in rats ovariectomized on Day 8 or Day 15 were studied by varying the time of progesterone implantation after ovariectomy. Progesterone implants were administered 8, 12 and 24 h after ovariectomy on Day 8 and 24, 36 and 48 h after ovariectomy on Day 15. On Day 8, progesterone replacement could be delayed to 8 h but not 12 h, while on Day 15, progesterone replacement could be delayed up to 36 h but not 48 h after ovariectomy without affecting fetal survival.     

Vocal turn-taking in a non-human primate is learned during ontogeny

Conversational turn-taking is an integral part of language development, as it reflects a confluence of social factors that mitigate communication. Humans coordinate the timing of speech based on the behaviour of another speaker, a behaviour that is learned during infancy. While adults in several primate species engage in vocal turn-taking, the degree to which similar learning processes underlie its development in these non-human species or are unique to language is not clear. We recorded the natural vocal interactions of common marmosets (Callithrix jacchus) occurring with both their sibling twins and parents over the first year of life and observed at least two parallels with language development. First, marmoset turn-taking is a learned vocal behaviour. Second, marmoset parents potentially played a direct role in guiding the development of turn-taking by providing feedback to their offspring when errors occurred during vocal interactions similarly to what has been observed in humans. Though species-differences are also evident, these findings suggest that similar learning mechanisms may be implemented in the ontogeny of vocal turn-taking across our Order, a finding that has important implications for our understanding of language evolution.     

Luteal luteinizing hormone receptors during the postovulatory period in the mare

Changes in serum luteinizing hormone (LH) and progesterone concentrations, number of luteal unoccupied LH receptors, receptor affinity constants, luteal weights and luteal progesterone concentrations were determined during the postovulatory period in the mare. The number of unoccupied LH receptors and receptor affinity was less during the early (Days 1-4) and late [Day 15 through 3rd day after start of corpus luteum (CL) regression] luteal phases than during the mid-luteal (Days 9-14) phase of the postovulatory period (P less than 0.01). The number of LH receptors per CL increased 21-fold (P less than 0.001) from Day 1 to Day 14. Receptor affinity increased 5-fold (P less than 0.001) from Day 1 to Day 13. Receptor number was highly correlated with receptor affinity (P less than 0.01) and both were highly correlated with serum and luteal progesterone (P less than 0.01). During regression of the CL, the number of LH receptors and receptor affinity decreased concomitantly with serum and luteal progesterone. Morphologically, luteal cell development and degeneration correlated with the change in receptor numbers, affinity constants and luteal and serum progesterone concentrations. Receptor number and affinity, luteal weight and serum and luteal progesterone concentrations did not differ between the CL from multiple ovulations. Random variations in the data observed between CL from multiple and single ovulations suggested that CL from the two groups were not different in structure and function. In summary, the above results suggest that major factors in regulation of progesterone secretion and maintenance of the equine CL are changes in the number of LH receptors and the affinity constants throughout the postovulatory period.     

MR imaging in the non-human primate: studies of function and of dynamic connectivity

Since its early development in the late 1940s, nuclear magnetic resonance has become a powerful tool for applications ranging from chemical analysis or the study of the structure of solids to biomedical investigations. In the early 1990s the potential of this technique for functional brain mapping was demonstrated, causing unprecedented excitement in both basic and clinical neuroscience. It was shown that by using the appropriate pulse sequences the so-called functional magnetic resonance imaging (fMRI) technique can be made sensitive to local magnetic susceptibility alterations produced by changes in the concentration of deoxyhemoglobin in venous blood vessels. This blood-oxygenation-level-dependent (BOLD) contrast mechanism was successfully implemented in awake human subjects, in small animals, and recently in the non-human primate--the experimental animal of choice for the study of cognitive behavior. Simultaneous imaging and electrode recordings promise new insights into the mechanisms by which large-scale networks in the brain contribute to the local neural activity recorded at a given cortical site. Moreover, the use of MRI-visible tracers and of electrical microstimulation applied during imaging proves to be ideal for the study of connectivity in the living animal.     

Regulation of functional differentiation of the placental villous syncytiotrophoblast by estrogen during primate pregnancy.

By using the baboon as an in vivo model for the study of the endocrinology of human pregnancy, studies in the authors' laboratories have shown that the primate placenta is an estrogen target tissue and that estrogen, via interaction with the estrogen receptor, regulates functional differentiation of the syncytiotrophoblast, which is manifest as an upregulation of key components of the progesterone biosynthetic pathway and the metabolism of corticosteroids critical to placental-fetal development. Thus, estrogen exerts specific stimulatory effects on the receptor-mediated uptake of low density lipoprotein by, and expression of, the P-450 cholesterol side-chain cleavage enzyme within the syncytiotrophoblast, thereby promoting the production of progesterone. Concomitantly, there is an estrogen-dependent developmental regulation of the 11beta-hydroxysteroid dehydrogenase enzyme system in the syncytiotrophoblast, which enhances transplacental oxidation of maternal cortisol to cortisone and leads to maturation of the fetal hypothalamic pituitary adrenocortical axis late in gestation. Consequently, estrogen has a central, integrative role in modulating the dialogue and signaling system operating between the placenta and fetus that results in the maintenance of pregnancy and the development of adrenocortical self-sufficiency that are essential for maturation of the fetus and neonatal survival after birth.     

Luteal production of steroids and prostaglandins during simulated early pregnancy in the primate: differential regulation of steroid production by chorionic gonadotropin

Stimulation of the primate corpus luteum (CL) by endogenous chorionic gonadotropin (CG) in early pregnancy, or by exogenous human (h)CG in simulated early pregnancy, results in a transient elevation of serum progesterone (P) and a persistent elevation of serum 17 beta-estradiol (E). Luteal prostaglandins (PG) may play a role in these responses. The objective of the current study was to correlate luteal PG production and steroidogenic response of CL in vitro with patterns of serum steroids during simulated early pregnancy. CL were removed from rhesus monkeys (n = 26) at 0 h, 9 h, 3 days, 6 days, and 10 days, during prolonged CG exposure of simulated early pregnancy. Dispersed cells were incubated in vitro at 37 degrees C for 8 h. Changes in basal production of P were not significantly correlated with patterns of serum steroids. Maximal stimulation of P production by hCG in vitro (stimulated minus basal) continuously declined (p less than 0.01) from 0 h (means +/- SE, 59.6 +/- 17.9 ng/ml) to 10 days (4.7 +/- 1.8 ng/ml) of simulated early pregnancy. In contrast to patterns of response to hCG, the level of enhancement in P production in response to a maximally stimulatory dose of dibutyryl (db) cyclic adenosine 3',5'-monophosphate (cAMP) declined (p less than 0.05) from 0 h (52.4 +/- 17.6 ng/ml) to 3 days (20.3 +/- 8.4 ng/ml), but was maintained through 10 days (23.7 +/- 11.6 ng/ml) of simulated early pregnancy. As such, desensitization to gonadotropin, which occurred in terms of P production, appears to involve an event subsequent to stimulation of adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Luteal LH receptors during the oestrous cycle and early pregnancy in the pig

The concentration, affinity constant and occupancy of the LH receptor have been measured in corpora lutea, from 29 pigs at Days 6--16 of the oestrous cycle, and from 25 pigs at Days 12--30 of pregnancy, by using 125I-labelled porcine LH tracer. Investigation of the specificity of the receptor showed that cross-reactions of other pituitary hormones were accounted for by their contamination with LH. Luteal concentration of unoccupied receptors doubled between Days 6 and 10 of the cycle, and decreased between Days 12 and 14; it increased 3-fold between Days 20 and 30 pregnancy, but was lower on Day 12 of pregnancy than at a comparable stage of the cycle. Concentrations of receptors occupied by LH increased early in the oestrous cycle, in parallel with the total receptor concentration; in pregnancy the percentage occupancy dropped dramatically as total receptor concentration increased between Days 20 and 30. Receptor affinity constants increased towards the end of the cycle and decreased between Days 20 and 30 of pregnancy. It is suggested that (1) the lower concentration of receptors in early pregnancy may reflect down regulation by circulating LH, concentrations of which are higher in early pregnancy than during the cycle; (2) the increase in receptor concentration between Days 20 and 30 or pregnancy may be due to a rise in circulating oestrogen levels; and (3) the decrease in occupancy at this time may be caused either by a decrease in affinity constant or by placental production of a chorionic gonadogrophin-like compound.     

Baby on board: olfactory cues indicate pregnancy and fetal sex in a non-human primate

Olfactory cues play an integral, albeit underappreciated, role in mediating vertebrate social and reproductive behaviour. These cues fluctuate with the signaller''s hormonal condition, coincident with and informative about relevant aspects of its reproductive state, such as pubertal onset, change in season and, in females, timing of ovulation. Although pregnancy dramatically alters a female''s endocrine profiles, which can be further influenced by fetal sex, the relationship between gestation and olfactory cues is poorly understood. We therefore examined the effects of pregnancy and fetal sex on volatile genital secretions in the ring-tailed lemur (Lemur catta), a strepsirrhine primate possessing complex olfactory mechanisms of reproductive signalling. While pregnant, dams altered and dampened their expression of volatile chemicals, with compound richness being particularly reduced in dams bearing sons. These changes were comparable in magnitude with other, published chemical differences among lemurs that are salient to conspecifics. Such olfactory ‘signatures’ of pregnancy may help guide social interactions, potentially promoting mother–infant recognition, reducing intragroup conflict or counteracting behavioural mechanisms of paternity confusion; cues that also advertise fetal sex may additionally facilitate differential sex allocation.     

Changes in endometrial vascular permeability during the periimplantation period in the ferret (Mustela putorius)

A highly localized increase in permeability of uterine blood vessels in the immediate vicinity of implanting blastocysts was first detected on the morning of the 12th day of pregnancy (290 h post coitum). The amount of extravasated dye which accumulated at implantation sites continued to increase through the evening of Day 13 (321 h p.c.). Blastocyst expansion, as indicated by small uterine swellings, preceded a detectable change in vascular permeability by about 10 h, suggesting that the timing of increased permeability is closely associated with initial blastocyst attachment to the uterine epithelium. The results do not support the hypothesis that prostaglandins are required for increased uterine vascular permeability as two doses of indomethacin (4 and 8 mg/kg body wt) administered 5 times/day failed to decrease endometrial vascular permeability. However, the 8 mg dose did cause a significant reduction in size and number of uterine swellings and delayed or inhibited attachment of the trophoblast to the uterine epithelium in 2 of 5 ferrets. These findings suggest that prostaglandins play an important role in the process of implantation that is unrelated to decidual formation as the ferret is an adeciduate species.     

Accumulation of RNA in blastocysts during embryonic diapause and the periimplantation period in the western spotted skunk

The in vivo incorporation of 3H-uridine into RNA was studied in delayed implanting and activated blastocysts obtained from 33 western spotted skunks. 3H-uridine was incorporated into RNA by all blastocysts; however, significantly more label was incorporated as blastocyst diameter increased. Activated blastocysts with diameters of 1.6 mm or greater on average incorporated 65 times more 3H-precursor in 5 hr than diapausing blastocysts with diameters of 1.1 mm or less. Polyadenylated RNA was likewise synthesized by delayed implanting and activated skunk blastocysts; however, the proportion of polyadenylated RNA synthesized by the former was greater than in the latter (43.9% vs. 27.5%). Our data suggest that the transition from embryonic diapause to fully activated blastocysts first occurs gradually for several days before entering a 1-2-day period of rapid development characterized by an abrupt increase in RNA accumulation.     

非人灵长类肠道微生物研究进展与展望

肠道微生物组被誉为动物的“第二套基因组”,与动物的个体发育、营养获取、生理功能、免疫调节等重要活动密切相关。非人灵长类在生态位、社会结构、地理分布以及进化上与人类相近,开展其肠道微生物研究不仅有助于了解灵长类的生态、保护和进化,而且对深入了解肠道微生物在人类进化中所发挥的作用也具有重要的参考价值。本文总结了影响非人灵长类肠道微生物变化的因素,包括系统发育、觅食、栖息地破碎化、年龄和性别、圈养方式以及社群生活,并探讨了肠道微生物研究在非人灵长类生态、行为、保护以及适应性进化方面的应用。未来,非人灵长类肠道微生物研究将为灵长类生态、进化和人类健康的研究提供新的视角,为灵长类的保护提供新的理论基础和研究方法。     

Cell type-specific expression of transforming growth factor-beta 1 in the mouse uterus during the periimplantation period

Immunohistochemistry and in situ and Northern blot hybridization were employed to determine temporal and spatial expression of transforming growth factor-beta 1 (TGF beta 1) in the mouse uterus during the periimplantation period. The polyclonal antisera anti-LC-(1-30) and anti-CC-(1-30), raised against two different preparations of a peptide corresponding to the amino-terminal 30 amino acids of TGF beta 1, were used for histochemical analyses because of their distinct staining patterns. Anti-LC shows intracellular staining, while staining by anti-CC is primarily extracellular. The colocalization of intracellular staining by anti-LC with in situ hybridization of TGF beta 1 mRNA in the luminal and glandular epithelia on days 1-4 of pregnancy (day 1 = vaginal plug) indicates that the epithelial cells are the primary sites of TGF beta 1 synthesis during the preimplantation period. On the other hand, staining of the extracellular matrix of the stroma by anti-CC during this period suggests an active accumulation of TGF-beta 1 that is synthesized in and secreted from the epithelia. While intracellular staining and accumulation of TGF-beta 1 mRNA in the epithelia were clearly evident on days 1-4, the extracellular staining showed temporal fluctuations. The clear extracellular staining of the stroma that was observed on day 1 was absent on day 2; moderate staining was again visualized in the stroma on day 3 and was markedly increased on day 4.(ABSTRACT TRUNCATED AT 250 WORDS)