Pregnant Chimpanzees Research Articles

Faecal parasites increase with age but not reproductive effort in wild female chimpanzees.

Energy investment in reproduction is predicted to trade off against other necessary physiological functions like immunity, but it is unclear to what extent this impacts fitness in long-lived species. Among mammals, female primates, and especially apes, exhibit extensive periods of investment in each offspring. During this time, energy diverted to gestation and lactation is hypothesized to incur short and long-term deficits in maternal immunity and lead to accelerated ageing. We examined the relationship between reproduction and immunity, as measured by faecal parasite counts, in wild female chimpanzees (Pan troglodytes schweinfurthii) of Kibale National Park, Uganda. While we observed higher parasite shedding (counts of eggs, cysts and larvae) in pregnant chimpanzees relative to cycling females, parasites rapidly decreased during early lactation, the most energetically taxing phase of the reproductive cycle. Additionally, while our results indicate that parasite shedding increases with age, females with higher fertility for their age had lower faecal parasite counts. Such findings support the hypothesis that the relatively conservative rate of female reproduction in chimpanzees may be protective against the negative effects of reproductive effort on health. This article is part of the theme issue 'Evolution of the primate ageing process'.

The role of the placenta in the initiation of spiral artery remodelling in an early pregnant chimpanzee uterus

IntroductionIn this study we evaluated the full extent of placental bed changes (centre to periphery) in a pregnant chimpanzee uterus, kept at the Museum for Central Africa in Tervuren, Belgium. According to placental size the specimen was equivalent to an 8 weeks pregnant human uterus. MethodsHistological sections from central to peripheral tissue blocks of the placental bed were stained to reveal the presence of trophoblast, endothelium, vascular smooth muscle and elastic laminae. As an indicator for early arterial remodelling, we evaluated endothelial nuclear rounding and subendothelial vascular changes within the maternal vasculature in decidua and adjacent inner myometrium. ResultsWhile interstitially invading trophoblasts were present, endovascular trophoblast invasion seemed about to start into one spiral artery outlet at the centre of the placental bed, confirming our previous impression of a later onset of endovascular trophoblast invasion as compared to the human. An early sign of spiral artery remodelling was rounding of the endothelial nuclei. This phenomenon was not related to the local presence of interstitial trophoblast. DiscussionEndothelial nuclear rounding turned out to be a feature of the placental bed as a whole, being significantly less prominent in the adjacent non-placental bed part of the uterus, indicating an effect of the presence of the placenta. The different time-course of early spiral artery remodelling in the chimpanzee as compared to the human may have had a significant impact upon our evolution.

Deep trophoblast invasion and spiral artery remodelling in the placental bed of the chimpanzee

Deep trophoblast invasion is usually considered to be a unique feature of human placentation as compared to other primates. Because of the occasional occurrence of preeclampsia in great apes, which in the human is associated with impaired deep invasion, this uniqueness may be questioned. The availability of two well-documented pregnant chimpanzee uteri in the Hubrecht Collection (Museum für Naturkunde, Berlin) allowed us to evaluate the extent of trophoblast invasion in this species. By adjusting currently used protocols, we obtained successful immunohistochemical staining for cytokeratin and α-actin, as well as Ulex europaeus agglutinin 1 (UEA1) lectin staining, in this archival material. In both specimens interstitial trophoblast invasion had occurred in both decidua and myometrium. Because of a lack of published data on fetal growth for this species, fetal sizes (7 cm and 13 cm) could not be strictly related to gestational ages and thus be compared with the time-course of human trophoblast invasion. However, since the earlier specimen did not show any endovascular trophoblast invasion in spiral arteries – in contrast to pregnant human uteri with equivalent fetal sizes – endovascular migration seems to begin at a different gestational age in the chimpanzee. In the later specimen endovascular trophoblast was associated with spiral artery remodelling in the inner myometrium, and this invasion was extended to include a radial artery, which at that stage still showed relatively intact vascular smooth muscle and elastic lamina. We conclude that invasion depth and spiral artery remodelling are basically similar in chimpanzees and humans, although the seemingly different time of onset may have implications for uteroplacental oxygen supply and fetal development.

Urinary steroids, FSH and CG measurements for monitoring the ovarian cycle and pregnancy in the chimpanzee.

Non-invasive methods for monitoring reproductive status of chimpanzee based on the measurement of urinary steroids and gonadotropins were examined. A typical pre-ovulatory urinary estrone conjugate (E1C) surge and post-ovulatory increase in pregnandiol glucuronide (PdG) were seen during the menstrual cycle. Urinary follicle stimulating hormone (FSH) showed two peaks over the infertile menstrual cycle. The earliest changes indicating pregnancy were a coincident rise in E1C and chorionic gonadotropin (CG) levels and a concomitant fall in FSH levels. Urinary PdG levels showed a prolonged rise. Urinary E1C in the pregnant chimpanzee was higher than during the menstrual cycle and increased with advancing gestation, with maximum levels occurring near term. In the case of stillbirth, E1C and CG levels from mid- through late-pregnancy were low and the prepartum progressive increase in E1C was not shown. The data presented here are of great practical value in captive breeding management of chimpanzees.

Metabolism of gonadotropins: comparisons of the primary structures of the human pituitary and urinary LH beta cores and the chimpanzee CG beta core demonstrate universality of core production.

The gonadotropins are a family of closely related heterodimeric glycoprotein hormones homologous in structure to disulfide-knot growth factors. Metabolic proteolytic processing in vivo of this disulfide cross-linked region results in urinary excretion of a residual highly stable core structure. The primary structure of the pituitary form of the hLH beta core was reported earlier, but it has proved difficult to isolate the urinary core, although antibodies to the pituitary core demonstrated its presence. By conventional and immunoaffinity methods, the urinary core has been isolated and its structure determined by both chemical and mass spectrometric methods. The urinary hLH beta core is the same as the pituitary-extracted hLH beta core, beta 6-40 disulfide bridged to beta 55-93, except that the pituitary core is more heterogeneous containing also beta 49-93. These findings imply a dual origin of urinary cores, both directly from a secreting tissue and by kidney processing of circulating hormone. We also found that pregnant chimpanzees excrete a CG beta core with a primary structure identical to that of the human CG beta core of pregnancy. In conclusion, gonadotropin core generation and urinary excretion of nearly identical gonadotropin metabolites is common among primates. Although possible biological functions of these core fragments remain unproven, they have diagnostic utility because of their stability and abundance.

Secretion of inhibin A and inhibin B throughout pregnancy and the early postpartum period in chimpanzees.

Plasma concentrations of inhibin A and inhibin B during pregnancy and early lactation in chimpanzees were determined by enzyme-linked immunosorbent assay (ELISA). Plasma samples were taken from five pregnant chimpanzees at 6-9, 10, 20 and 25 weeks of pregnancy, and following parturition. Throughout pregnancy and the early postpartum period, circulating inhibin A and inhibin B concentrations remained low, at similar levels to those during the normal menstrual cycle in chimpanzees. Concentrations of inhibin A in the placental homogenate were high enough to be measured by the ELISA and by bioassay, whereas circulating inhibin bioactivities in late pregnancy were too low to be measured. Plasma concentrations of FSH remained low with no significant changes throughout pregnancy and the postpartum period. Plasma concentrations of oestradiol-17beta and progesterone at 25 weeks of pregnancy were much higher than normal menstrual cycle levels. It was concluded that in chimpanzees the levels of circulating inhibin A and inhibin B remained low throughout pregnancy and the early postpartum period, and that the concentrations of bioactive dimeric inhibin did not increase towards the end of pregnancy. The suppression of circulating FSH levels during pregnancy is suggested to be controlled by steroid hormones that increased significantly in late pregnancy, and the present findings further suggest that the secretory pattern and role of inhibin during pregnancy in chimpanzees may be different from that in human and other primates.

Systemic and Mucosal Immunity Is Elicited after Both Intramuscular and Intravaginal Delivery of Human Immunodeficiency Virus Type 1 DNA Plasmid Vaccines to Pregnant Chimpanzees

DNA vaccines encoding human immunodeficiency virus type 1 (HIV-1) env/rev and gag/pol were delivered intravaginally (IVAG) and intramuscularly (IM) to 2 pregnant chimpanzees. Vaccination was well tolerated and each chimpanzee developed antibodies (up to 1 year later) to both vaccines. Placental transfer of anti-Env and anti-Gag IgG was demonstrated in both maternal/infant pairs. Specific IgG was also demonstrated in saliva, vaginal, and rectal washes after IVAG immunization. Predominantly anti-HIV-1 IgA was detected in the milk of both mothers after both IM and IVAG immunization. Cellular responses included Gag-specific proliferation of lymphocytes and cytotoxic T lymphocytes against both antigens. These data suggest a strategy for induction of mucosal and systemic responses after both IM and IVAG delivery of DNA vaccines in a primate model and could ultimately be useful in lowering maternal-to-fetal transmission of HIV-1, perinatally and through breastfeeding.

Characterization of the mucosal immune response in breast milk after peroral immunization of chimpanzees ( Pan troglodytes) with Streptococcus mutans

The characteristics of the mucosal immune response to Streptococcus mutans cells, antigen A, antigen B, glucosyltransferases and glucan-binding proteins were examined in four pregnant chimpanzees that had been immunized perorally with Strep. mutans. Six pregnant chimpanzees served as non-immunized controls. None of the chimpanzees harbored S. mutans. Samples of milk were collected from all animals throughout the experiment. Peroral immunization resulted in an overall 17-fold median increase in SIgA in milk. Although SIgA1 comprised almost two-thirds of milk SIgA, Strep. mutans whole-cell antibody activity was contained predominantly in the SIgA2 subclass. The difference between the specific activities of anti- Strep. mutans SIgA1 and SIgA2 antibodies compared over time reached the borderline of statistical significance ( p=0.08). The avidity of anti- Strep. mutans antibodies was low in three of four chimpanzees and there was no evidence of affinity maturation. SIgA antibodies from the milk of all four immunized chimpanzees recognized antigen A. In three animals these antibodies were restricted to the SIgA1 subclass and, in one animal, anti-A antibodies were confined to SIgA2. Antibodies from all of the immunized chimpanzees recognized degradation products of antigen B in both the SIgA1 and the SIgA2 subclasses. Only two of four immunized chimpanzees responded to glucosyltransferases and these antibodies were restricted to the SIgA1 subclass. None of the chimpanzees responded to the 74-kDa glucan-binding protein. However, three animals produced SIgA1 antibodies against the 59-kDa glucan-binding protein and two of these also produced SIgA2 antibodies against this protein.

Anogenital swelling in pregnant chimpanzees of Gombe National Park.

Previous studies show that anogenital swelling patterns of pregnant chimpanzees in captivity are correlated with the female's age during pregnancy and are associated with changes in social behavior. The purpose of the present study was to investigate whether the anogenital swelling patterns of free-ranging pregnant chimpanzees resemble those reported for captive chimpanzees. We reviewed the records of 47 pregnancies experienced by 20 female chimpanzees living in Gombe National Park from 1975 to 1992. Percentage scores for swelling during each trimester and for the overall occurrence of various levels of swelling were obtained by dividing the frequency by the total number of days the subject was observed (i.e., 28 days of swelling/165 days observation = 17.2% anogenital swelling for that pregnancy). Subjects exhibited anogenital swelling an average of 25.1% of the days observed during pregnancy, yet reached maximum only 9.4% of the time. Anogenital swelling occurred less frequently as pregnancy progressed, averaging 40.8, 27.3, and 2.7% in the first, second, and third trimesters, respectively. As seen in captive chimpanzees, young pregnant females at Gombe showed anogenital swelling more often than did older ones (r = -.65, P < .0001). These findings are consistent with reports of behavior associated with anogenital swelling (e.g., intercommunity transfer of young females exhibiting anogenital swelling). © 1993 Wiley-Liss, Inc.

Partial hydatidiform mole in a pregnant chimpanzee (Pan troglodytes)

AbstractUntil now, the occurrence of hydatidiform mole in non‐human primates has not been documented. This report presents a case in which a stillborn fetus, associated with a partial hydatidiform mole, was found at necropsy in the uterus of a pregnant chimpanzee (Pan troglodytes) which had suddenly died. Hydropic swelling of the chorionic villi and proliferation of trophoblastic cells were present. The trophoblast was stained enzyme‐immunohistochemically with human chorionic gonadotropin (hCG) and pregnancy‐specific‐β1‐glycoprotein (SP1). The concentrations of hCG and SP1 in maternal serum were high, 1,350 mIU/ml and 1,000 ng/ml, respectively. The distribution of DNA content of the cytotrophoblast in the molar villi shifted from diploid to an aneuploid pattern. © 1993 Wiley‐Liss, Inc.

Social behavior and genital swelling in pregnant chimpanzees (Pan troglodytes).

Previous reports of increased sexual activity associated with genital swelling during chimpanzee pregnancy have suggested that the tumescent pregnant female may be regarded as a regularly cycling estrous female. Analysis of additional data from seven pregnant and eight cycling females, however, indicated that tumescent pregnant females differed from cycling females in some social interactions with males. As in earlier reports, pregnant females were more receptive to male-initiated copulatory bouts. In addition, pregnant females initiated grooming bouts with males much less frequently than did cycling females, and males spent less time grooming and less frequently inspected the genitals of pregnant than cycling cagemates. This tendency to decrease social interaction during pregnancy is consistent with field reports that pregnant chimpanzees prefer the company of their offspring and other noncycling females. In addition, the genital swelling patterns of 40 chimpanzee pregnancies were analyzed. Length of gestation averaged 231.5 days. Although a high degree of individual variation existed, females were swollen an average of 41% of the days observed, yet reached maximum swelling only 8.7% of the time. Genital swelling was less frequent during the third trimester, averaging 50.5, 47.9, and 22.6% tumescent days in each trimester. Young pregnant females showed maximum swelling more often than did older females. This finding is discussed with respect to field reports of intercommunity transfer of young, tumescent female chimpanzees.

Immunological Relationships of Human and Subhuman Primate Pregnancy-Associated Plasma Proteins

(1) Four pregnancy-associated plasma proteins cross-reactive with antibodies to the human pregnancy proteins were detected in several species of pregnant subhuman primates. In the case of the two apes studied (chimpanzee and orangutan), these appeared to be immunologically identical to the human PAPPs (PAPP-A, -B, -C, and HCS). In the old world monkeys analyzed, equivalent partially cross-reactive PAPPs were found; while in the new world squirrel monkey, only faint traces of cross-reactive PAPP-C and HCS were observed with the most sensitive methods used. (2) As in the human, these proteins appeared to be specific for pregnancy, not being detectable in nonpregnant animals, female or male. (3) The pregnant chimpanzee possessed significantly higher concentrations of PAPP-A and PAPP-C than did women at an equivalent stage of pregnancy, while the HCS and PAPP-B levels appeared to be approximately the same. (4) The primate PAPP-C analogues were more complex than human PAPP-C, often revealing multiple gel diffusion patterns with subfractions of differing electrophoretic mobilities. (5) Based on the changes of electrophoretic mobility upon exposure to neuraminidase, the subhuman primate as well as human PAPP-A and PAPP-C appeared to be glycoproteins containing sialic acid. (6) In the chimpanzee and rhesus monkey, as in the human, the levels of PAPP-A, PAPP-C, and HCS were appreciably higher during the third trimester of pregnancy than they were during the second trimester.

Diagnosis of pregnancy in chimpanzees using the nonhuman primate pregnancy test kit.

The usefulness of The Nonhuman Primate Pregnancy Test kit for diagnosis of pregnancy in chimpanzees was determined. This hemagglutination inhibition test for urinary chorionic gonadotropin accurately indicated conception by positive responses in 151 to 153 specimens collected between 20 and 133 days after the estimated day of fertilization. The rate of false positive responses did not exceed 1%.

Serial serum levels of gonadotropins, prolactin and sex steroids in the nonpregnant and pregnant chimpanzee.

Serum levels of FSH, LH, chorionic gonadotropin (CG), prolactin, estrone (E1), estradiol-17Beta (E2), estriol (E3) and progesterone were measured at 2-3-day intervals in 4 chimpanzees through 2-3 menstrual cycles, and serially through subsequent pregnancies. The hormone patterns of the menstrual cycles were similar to those in man, with high levels of FSH in the early follicular phase, followed by rising E2 concentrations to a peak (up to 35 ng/dl) at or just before a midcycle LH/FSH peak. In most cycles there was a secondary E2 rise and progesterone rose to values above 500 ng/dl during the luteal phase. There was no consistent pattern in prolactine levels through 3 menstrual cycles. A simultaneous increase in E2 and LH/CG levels and a fall in FSH about 10 days postovulation indicated fertilization and implantation. Other early signs of pregnancy were persistent luteal range progesterone concentrations and rising levels of E1 and E3. Peak CG levels (56-154 IU/ml) occurred 30-50 days after the midcycle LH/FSH peak, followed by a decline and then a small secondary rise to (to 1 IU/ml) before term. E1, E2 and E3 levels rose more rapidly after 80 days to a peak at term (E1: 180-300 ng/dl; E2: 500-800 ng/dl; and E3:400-1000 ng/dl). Progesterone levels showed one peak coincident with the CG peak, and a secondary rise after about 80 days to maximal values at term of 49-120 ng/ml. Prolactin levels increased during pregnancy with irregular fluctuations (7-127 ng/ml). These findings indicate in contrast to observations in rhesus monkeys and baboons, that the hormonal patterns during pregnancy in the chimpanzee are remarkably similar to those in man. Thus, the chimpanzee should prove to be an ideal model for research directly applicable to human reproduction.

Urinary chorionic gonadotropin in middle and late pregnancy in the chimpanzee.

Twenty-four hr urine samples were collected at 7-day intervals from two pregnant chimpanzees during middle, late and post-partum phases of gestation. An aliquot of each sample was prepared by acetone precipitation and the remainder was extracted by a kaolin-acetone method. Chimpanzee chorionic gonadotropin (ChCG) activity was determined by radioimmunoassay (RIA) and rat uterine weight (RUW) bioassay methods. Second International Standard Human Chorionic Gonadotropin (HCG) was a suitable reference preparation for both assay methods. Samples prepared by acetone precipitation showed more ChCG activity in RIA and RUW bioassay than those extracted by kaolinacetone procedures, but in general, patterns of change were similar in samples prepared by both methods. ChCG levels were elevated during midgestation. Beginning about 40–50 days before either abortion or normal delivery, the ChCG levels fell precipitously until about 25 days prior to expulsion of the placenta. A brief rise in ChCG excretion was evident at t...

Chorionic gonadotropin secretion during pregnancy in the chimpanzee (Pan troglodyte).

SummaryQuantitative alterations in urinary gonadotropin excretion were studied throughout pregnancy in two chimpanzees (Pan troglodyte). Weekly urine samples were collected following mating and gonadotropic activity determined by the increase in ovarian weights of immature female rats. Gonadotropic activity was first detected during weeks 1 and 2 postmating, and had reached peak titers by days 30 to 40. These levels persisted for 2 to 3 weeks and declined rapidly, thereafter, to low, but detectable, levels which were maintained until 1 to 3 weeks prepartum. Reproductive cyclicity as determined by periodic swelling and detumescence of the genital and anal region disappeared during lactation. Biological and immunological tests of extracts from pregnant chimpanzee urine indicate a close relationship to human chorionic gonadotropin and the temporal changes in gonadotropic titers occurring throughout gestation are comparable to those reported for the human.The authors thank Drs. Y. T. and S. C. Li for their he...

Glomerular capillary endothelial swelling in a pregnant chimpanzee

An example of glomerular capillary endothelial swelling in a primigravid chimpanzee is reported. This lesion is considered to be nearly pathognomonic for pre-eclampsia-eclampsia in humans, and its occurrence in a pregnant chimpanzee must therefore be given considerable weight despite the lack of confirmatory clinical data. Such a lesion has not been previously described in an animal.

The metabolism of estrone- 14C in a pregnant chimpanzee

Following injection of a tracer dose of estrone-16- 14C into a pregnant chimpanzee, radioactive 17 β-estradiol, estriol, and 2-methoxyestrone were identified in the urine. The specific activity of the urinary estrone and estradiol was about 100 times that of the estriol, although the latter steroid was present in large amounts. Almost half of the radioactive dose was excreted as unconjugated steroid. The remainder was excreted largely as glucuronosides and sulfates. Small amounts of a conjugate of estrone which was not split either by solvolysis or by β-glucuronidase were detected.

ANALYSES OF URINE OF THE CHIMPANZEE FOR ESTROGENIC CONTENT DURING VARIOUS STAGES OF THE MENSTRUAL CYCLE

The urine of prognant woman and mares is an abundant source of both estrogenic and gonadotropic substances (1, 2). Some other mammals excrete relatively little during pregnancy (3). Recovery of considerable amounts of estrogenic material from the urine of pregnant chimpanzees has been repoted in an earlier paper (4). Yields ranging from 170 to 620 mouse units per liter of urine were obtained at various stages of pregnancy. Chimpanzee placentas also proved to be a good source of estrogenic material, being similar to the human in this respect. At the same time Zuckerman (5) reported the diagnosis of pregnancy by series of Aschheim-Zondek tests for anterior pituitarylike hormone in urine from these pregnant chimpanzees. In recent years perfection of extraction methods has made possible assays of small amounts of excreted estrogenic materials in the urine of non-pregnant animals. Of greatest interest has been the variation in the amount excreted at different times in the menstrual cycle in women (6, 7, 8, 9, ...