Correlation between urinary pregnanediol glucuronide and basal body temperature in female orangutans Pongo pygmaeus.код для вставкиСкачать
American Journal of Primatology 34:275-281 (1994) BRIEF REPORT Correlation Between Urinary Pregnanediol Glucuronide and Basal Body Temperature in Female Orangutans, Pongo pygmaeus CHERYL S. ASA', FRANK FISCHER', EMILEE CARRASCO', AND CYNTHIA PURICELLI' ' S t . Louis Zoological Park, St. Louis, Missouri; 'The Population Council, New York, New York Changes in basal body temperature (BBT) in relation to the menstrual cycle were investigated in three adult female orangutans (Pongo pygmaeus). In particular, the relationships of BBT to urinary estrone conjugates (EC) and to pregnanediol glucuronide (PDG) were examined using two of the females during two cycles each. Radiotelemetry transmitters were implanted peritoneally to record core body temperatures. Radio signals were received approximately every 2 min, 24 h per day. Because temperatures during the period 0300-0400 h were most stable (i.e., were less likely to be affected by confounding variables such a s activity), a mean of these values was used to calculate daily BBT. BBT showed a highly significant positive correlation with PDG but not with EC. Menstrual phases were associated with declining or trough levels of BBT. Although changes in BBT were not sufficiently distinct to predict or to precisely identify the time of ovulation, the strong association between BBT and PDG suggests that radiotelemetry of BBT may be useful in monitoring ovarian cycles, especially the luteal phase, in this species. 0 1994 Wiley-Liss, Inc. Key words: body temperature, pregnanediol, telemetry, orangutan, ape, menstrual cycle INTRODUCTION The cyclicity of body temperature during the ovulatory cycle, first recognized almost a century ago [Giles, 18971, has been ascribed to the thermogenic property of progestins [Barton & Wiesner, 1945; Buxton & Atkinson, 19481. However, factors other than progesterone can influence body temperature, including activity, arousal, handling [Balin & Wan, 19683, anesthesia [Wixson et al., 19871, and circadian rhythms in basal metabolic rate and sleep [Aschoff, 19821. Peripheral measurement (e.g., rectal or oral) may not reflect the more stable core basal body Received for publication September 17, 1993; revision accepted January 25, 1994. Emilee Carrasco's current address is Biopsychology Subprogram, Hunter College, 692 Park Avenue, New York, NY 10021. Address reprint requests to Cheryl Asa, St. Louis Zoological Park, Forest Park, St. Louis, MO 63110. 0 1994 Wiley-Liss, Inc. 276 I Asa et al. temperature (BBT). In addition, vaginal temperature is affected by changes in blood flow [Abrams & Bazer, 19731, also related to the reproductive cycle, but correlated with estradiol [Abrams et al., 19731, not progesterone. Thus, it is not surprising that earlier investigations that were unable to control for these variables produced variable results. In particular, studies to detect or predict ovulation for timed intercourse or inseminations have met with limited success (e.g., human: Bauman ; gibbon, Hylobates lar: Carpenter ; rhesus, Macaca mulatta: Erikson ; dog, Canis familiaris: Christie & Bell ), perhaps because they require more precision than peripherally measured temperature can provide, and because the cyclic increase in progesterone occurs after ovulation in most species, with highest pregnancy rates following artificial insemination the day prior to temperature rise [Newill & Mauricekatz, 19821. However, biotelemetry can remotely monitor temperature during periods of sleep from a n intra-peritoneal transmitter to control most variables, and thus, more closely approximate true BBT. This study evaluated the ability of temperature telemetry to monitor the menstrual cycle of the orangutan as compared to urinary estrone and pregnanediol-glucuronide levels and presence of menstrual blood. MATERIALS AND METHODS Two females (#78217: 13 years; #75201: 16 years) were nulliparous, due to deficits in the species-specific social responses necessary for mating resulting from human rearing. The others (#911006: 22 years; #921216: 24 years) had at least one infant. They were housed with a n adult male, also sexually incompetent due to rearing condition, in a n indoor enclosure (approximately 62 x 30 m) during the day (0900-1645 h) but singly overnight in sleeping quarters (8 x 12 m or 6 x 10 m) so that morning urine could be collected. Urine was aspirated by syringe each morning from the drains of females 75201 and 78217 from 16 May to 6 July 1991 (Julian days 136 to 187), and held at -80°C until assay. Between 1December 1991 and 25 April 1992 (Julian days 335,1991, to 115, 1992), urine was tested for menstrual blood (Ames Hemastix; Miles, Inc., Elkhart, IN). Urine was also collected and tested with Hemastix, but not assayed, from female 911006 from 6 December 1991, and from 921216 from 1 May 1993 through 28 December 1993. On 8 May 1993, the synthetic progestin medroxy-progesterone acetate (DepoProvera; Upjohn Co., Kalamazoo, MI) was administered by intramuscular injection (10 mg/kg body weight) to females 911006 and 921216. Estrone conjugates (EC) and pregnanediol glucuronide (PDG) were measured as in Chaudhuri e t al. [19881, modified for the orangutan (PDG antiserum: Department of Biochemistry and Molecular Biology, University College, London, UK). Serial dilutions of orangutan urine had displacement curves parallel to that obtained with increasing amounts of estrone sulfate (31.25-500 pg) or PDG (622,000 pg). Assay sensitivity was 7.5 pg/tube (EC) and 31.25 pglml (PDG); intraassay and inter-assay (n = 4) coefficients of variation (CVs) based on replicates of a n orangutan urine pool werg 2.6% and 24.8% (EC) and 4.7% and 26.9% (PDG), respectively. (Although standard curves were consistent, relatively high interassay CVs were due to a shift in values of pooled urine reference samples.) Steroid values are expressed relative to urinary creatinine concentrations [Taussky, 19541. Temperature transmitters (Wildlife Materials, Inc., Carbondale, IL; coated with a n inert material, 7 x 3.8 x 1.8 cm, 50 g, 2 year battery life) were inserted via a 5 cm incision into the abdominal cavities of females 75201 and 78217 under general anesthesia (isoflurane) on 16 May 1991 (Julian day 136), into female Orangutan Body Temperature and Progestin I 277 ORANGUTAN 782 17 r 25 r 300 4 250 TI z m 200!3 15OP 3 09 100, q 140 150 160 170 180 190 200 210 JULIAN DATE 1991 menstrual phase I 300 - 250 - 200 = ,- 3 - 150y - - 100 -0 z: 20 t r3 TI Z IS? 3 09 10 g - 25 3 ;; 9 v 5 0 ! - 5 - 0 O 0 0 911006 on 8 September 1992 (Julian day 2521, and into female 921216 on 7 January 1993 (Julian day 737). The automatic data collection system, consisting of a Commodore computer and receiver (Wildlife Materials, Inc.), continuously sampled temperatures at approximately 2 min intervals. One antenna was directed toward the communal enclosure and another toward the sleeping quarters. Quantatative comparison of hourly standard errors on 24 h circadian temperature graphs showed 0300-0400 h to be most stable. Thus, daily means generated from that hour were used as the BBT. Daily concentrations of EC and PDG were compared to BBT using Pearson Product Moment Correlation (Number Cruncher Statistical System, Kaysville, UT). RESULTS Concentrations of PDG, but not those of EC, were significantly correlated with BBT (female 78217: P 5 0.001; r2 = 0.65, df = 61; female 75201: P 5 0.001; r2 = 0.60, df = 58, one-tailed test). There were more fluctuations in the BBT curve for female 78217 than those for female 75201 (Fig. l ) , as reflected in differences in cycle minima and maxima (1.53"C: 78217; 1.29"C: 75201). Sustained increases in PDG were preceded by EC peaks and followed by menstrual flow (Fig. 1).A second, more attenuated elevation in EC was seen during 278 I Asa et al. 38 ORANGUTAN 75201 1 333 I I 1 352 7 28 - 1 - 52 1 76 - I I 97 119 JULIAN DATE 1991-92 38 ORANGUTAN 70217 1 333 352 7 28 - I . I d 52 76 97 119 JULIAN DATE 199 1-92 menstrual phase - menstrual phase #9llOOS - Fig. 2. Cyclic changes in basal body temperature of two female orangutans in relation to the menstrual phase. periods of increased PDG excretion. Menstrual flow was first detected a s BBT, PDG, and EC declined. Although BBT appeared to increase several days before PDG, decreases were coincident. PDG was undetectable in this assay system during apparent inter-luteal phases, but, despite the strong correlation between these parameters, BBT showed some fluctuation during these periods, especially in female 78217. using only BBT and menstrual Continued cycle monitoring of three fem: flow revealed menstrual phases associated witl%Iecreases in BBT (Figs. 2,3). An menstrual cycle appeared to exception occurred in female 78217 (Fig. 21, w t phase-shift in association with that of female 9ilh)06. Mean menstrual cycle lengths for the three females (day 1 = first day of enstrual flow) were 34 ? 2 days (n = 5 cycles) for female 78217, 31.7 f 0.6 days (n = 6 cycles) for female 75201, and 27 f 3.3 days (n = 9 cycles) for female 911 96. Depo-Provera treatment resulted in immediate, sustained temperature elevation in both females (Fig. 4). - DISCUSSION The highly significant correlation between PDG in this study contrasts with results for the langur, Presbytis entellus [Lohiya et al., 19881, and the chimpanzee, Pan troglodytes [Graham et al., 19771, perhaps attributable to differences in methodology. Langur temperatures, measured vaginally with a thermometer during Orangutan Body Temperature and Progestin I 279 37 ORANGUTAN 9 11006 I - u v z2 36 - ffi 4 w a 2 35 - E- 260 280 300 320 340 360 JULIAN DATE 1992 menstrual phase - Fig. 3. Cycle changes in basal body temperature of female 911006 in relation to the menstrual phase. FEMALE 9 1 1006 1 37.5 37.0 W 5c 2a 5+ 36536.0 - 35535.0 - ' 34.5 , I I I I I I I I I 1 1120 1140 1160 1180 1200 1220 1240 1260 1280 1300 1320 FEMALE 921216 37.5 w - 370- K 3 + 4 cx w a 365- W I + 36.0 Depo-Provera - I restraint, may have been elevated from handling. In addition, vaginal temperatures can be affected by estrogen-stimulated local blood flow increases [Abrams & Bazer, 1973; Abrams et al., 19731. The chimpanzee temperatures, although measured remotely, used transmitters placed intra-muscularly that may have been affected by muscle-generated heat. Although White et al.  did not measure PDG or progesterone, they did find a sustained luteal increase in BBT for the pigtail macaque, Macaca nemestrzna, using subdermal radiotransmitters. Likewise, in chimpanzees [Graham et al., 19771, BBT and PDG were not correlated, but there was a sustained BBT increase during the luteal phase. 280 I Asa et al. In the present study, in three of four cycles, BBT also appeared to rise with the EC peak and then dip before exhibiting the sustained luteal increase. Periovulatory changes in BBT reported for other species include a decrease a t the time of the serum estradiol peak in the langur [Lohiya et al., 19881, a decrease and then a n increase at ovulation in the rhesus [Balin & Wan, 19681, a decrease the day after the urinary estrone peak in the chimpanzee [Graham et al., 19771, a decrease the day of the luteinizing hormone peak in the human [Morris et al., 19761, and a spike the day of estrus for domestic cattle, Bos taurus [Wrenn et al., 1958; Zartman et al., 19831. Because little if any preovulatory progesterone has been detected in these species, hyperemia associated with the estrogen spike or a n as-yet-unsuspected factor may be responsible. The absence of a n absolute correspondence between the menstrual phases and changes in BBT shown by female 78217 was possibly due to the influence of female 911006 (Fig. 2). BBT for female 78217 declined slightly at the time of her own menstrual phase, rose briefly, and then declined again with the menstrual phase of Female 911006. During subsequent cycles, the menstrual phases of the two females were synchronized and the BBT curve of female 78217 once again appeared regular. Although there has been no study of tendencies toward menstrual cycle synchrony in orangutans, one report suggests that introduction of a new female can affect cycles and perhaps fertility in this species [Zucker et al., 19871. The ability of Depo-Provera, a synthetic progestin, to stimulate a sustained BBT elevation confirms the positive association between body temperature and both endogenous and exogenous progestins. The duration of the effect is surprising, however. The absence of menstrual cycles during this entire period suggests that circulating levels of progestin were sufficient to suppress ovarian activity as well as to maintain elevated BBT. In conclusion, although based on only two cycles from each of two females, the correlation between BBT and urinary PDG was highly significant. In addition, during continued monitoring of multiple cycles in these and a third female, BBT was elevated during the predicted luteal period, defined by dates of menstrual blood in urine. Exogenous, synthetic progestin administration also produced sustained BBT elevation. ACKNOWLEDGMENTS We thank M. White and R. Rouggly for urine collection, Dr. R. Junge for surgical installation of transmitters, G. London, S. Taylor, P. Monk, K. Kearns, and K. VanKoevering for computer data transcription, and I. Porton and Dr. W.J. Boever for advice. This work was supported in part by a grant from the NixonGriffis Fund for Zoological Research. REFERENCES Abrams, R.M.; Bazer, F. Cyclic variations in vaginal thermal conductance in ewes. AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY 17:480-482, 1973. Abrams, R.M.; Thatcher, W.W.; Bazer, F.W.; Wilcox, C.J. Effect of estradiol-17P on vaginal thermal conductance in cattle. JOURNAL OF DAIRY SCIENCE 56:1058-1062, 1973. Aschoff, J . The circadian rhythm of body temperature as a function of body size, pp. 173-188 in A COMPANION TO ANIMAL PHYSIOLOGY. C.R. Taylor; K. Johansen; L. Bolis, eds. Cambridge, Cambridge University Press, 1982. Balin, H.; Wan, L.S. The significance of circadian rhythms in the search for the moment of ovulation in primates. FERTILITY AND STERILITY 19:228-243, 1968. Barton, M.; Wiesner, B.P. Thermogenic effect of progesterone. LANCET 2:671-672, 1945. Bauman, J.E. Basal body temperature: Unreliable method of ovulation detection. Orangutan Body Temperature and Progestin I 281 FERTILITY AND STERILITY 36:729733,1981. Buxton, C.L.; Atkinson, W.B. Hormonal factors involved in the r e d a t i o n of basal body temperature durinGhe menstrual cycle and pregnancy. JOURNAL OF CLINICAL ENDOCRINOLOGY 8:544-549, 1948. Carpenter, C.R. The menstrual cycle and body temperature in two gibbons (HyZobates Zar). ANATOMICAL RECORD 79: 291-296,1941. Chaudhuri, M.; Kleiman, D.G.; Wildt, D.E.; Bush, M.; Frank, E.S.; Thau, R.B. Urinary steroid concentrations during natural and gonadotrophin-induced oestrus and pregnancy in the giant panda (Ailuropoda melanoleuca). JOURNAL OF REPRODUCTION AND FERTILITY 84:23-28, 1988. Christie, D.W.; Bell, E.T. Changes in rectal temperature during the normal oestrous cycle in the beagle bitch. BRITISH VETERINARY JOURNAL 127:93-98, 1971. Erikson, L.B. The temperature variation in the rhesus monkey under normal and experimental conditions. NATURE 18623384, 1960. Giles, A.E. The cyclical wave theory of menstruation with observations on the variations in pulse and temperature in relation to menstruation. TRANSACTIONS OF THE OBSTETRICS SOCIETY OF LONDON 39:115-126,1897. Graham, C.E.; Warner, H.; Misener, J.; Collins, D.C.; Preedy, J.R.K. The association between basal body temperature, sexual swelling and urinary gonadal hormone levels in the menstrual cycle of the chimpanzee. JOURNAL OF REPRODUCTION AND FERTILITY 50:23-28, 1977. Lohiya, N.K.; Sharma, R.S.; Puri, C.P.; David, G.F.X.; Anand Kumar, T.C. Reproductive exocrine and endocrine profile of female langur monkeys, Presbytis entellus. JOURNAL OF REPRODUCTION AND FERTILITY 82:485-492, 1988. Morris, N.M.; Underwood, L.E.; Easterling, W. Temporal relationship between basal body temperature nadir and luteinizing hormone surge in normal women. FERTILITY AND STERILITY 27:780-783,1976. Newill, R.G.D.; Mauricekatz, F.C.P. The basal body temperature chart in artificial insemination of donor pregnancy cycles. FERTILITY AND STERILITY 38:431438, 1982. Taussky, H.H. A microcolorimetric determination of creatinine in urine bv the Jaffe reaction. JOURNAL OF BIOLOGICAL CHEMISTRY 208:853-861,1954. White, R.J.; Blaine, C.R.; Blakley, G.A. Detecting ovulation in Macaca nemestrina by correlation of vaginal cytology, body temperature and perineal tumescence with laparoscopy. AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 38:189194, 1973. Wixson, S.K.; White, W.J.; Hughes, H.C.; Lang, H.C.; Marshall, W.K. The effect of pentobarbital fentanyldoperidol, ketamine-xylazine and ketamine-diazepam on core and surface body temperature regulation in the adult male rat. LABORATORY ANIMAL SCIENCE 37343-749, 1987. Wrenn, T.R.; Bitman, J.; Sykes, J. Body temperature variations in dairy cattle during the estrous cycle and pregnancy. JOURNAL OF DAIRY SCIENCE 41:1071-1080, 1958. Zartman, D.L.; Hallford, D.M.; Tierney, L.A.; Hussain, M.Y. Reproductive characteristics of Holstein heifers fitted with intravaginal temperature transmitters. THERIOGENOLOGY 19:541-554, 1983. Zucker, E.L.; Robinett, D.S.; Deitchman, M. Sexual resurgence and possible induction of reproductive synchrony in a captive group of orangutans. ZOO BIOLOGY 6:3139, 1987.