Puberty in the male chimpanzee: time-related variations in circulating inhibin.

Circulating immunoreactive inhibin concentrations were determined in male chimpanzees (n = 12) during a 36-mo period starting 18 mo before the onset of pubertal testicular growth (Po). Serum levels of inhibin started to increase, together with LH and testosterone, 6 mo before a rise in FSH and Po. Before Po, inhibin was not related to gonadotropins but was related to testosterone levels (r = 0.263; p < 0.005; R2 = 7%). After Po, inhibin remained related to testosterone (r = 0.289, p < 0.01) but became inversely related to gonadotropins; FSH was the best predictor (r = -0.382, p < 0.0005; R2 = 30%) of this relationship. During the progressive rise in circulating inhibin, FSH increased and plateaued during 9 mo, then dropped to prepubertal levels. These findings suggest that a specific closed-loop negative feedback system for the secretion of FSH by inhibin is not functional before the onset of puberty in the chimpanzee. This feedback system seems to fully operate several months after the LH rise and may be related to the complete maturation of both Sertoli cells and spermatogenesis.

Puberty in the male chimpanzee: progressive maturation of semen characteristics.

Cellular and biochemical characteristics of semen obtained by masturbation were studied in 5 pubertal chimpanzees during 1.5 yr. The dental age corresponding to the beginning of the pubertal testicular growth (Po) ranged from 5.0 to 8.3 years (mean = 6.7 +/- 1.2 yr). Time-related variations of all studied parameters were analyzed according to Po and, therefore, independently of the dental age. The emission of first ejaculates, and therefore the onset of activity of the accessory sex gland, was estimated to occur 4 mo after Po. The ejaculate volume (n = 132, r = 0.704, p less than 0.001), as well as the total amounts of l-carnitine (n = 65, r = 0.649, p less than 0.001), fructose (r = 0.522, p less than 0.001), citrate (r = 0.748, p less than 0.001), and acid phosphatase (r = 0.756, p less than 0.001) increased with time. First-obtained ejaculates contained no spermatozoa. Spermarche was estimated to occur 9.4 mo after Po. Total sperm count increased with time (r = 0.595, p less than 0.001). The motility and viability of spermatozoa increased with time (r = 0.474, p less than 0.01 and r = 0.632, p less than 0.001, respectively) while their morphology did not vary. The volume of the liquefied fraction and its content in free spermatozoa considered as available for fecundation remained low until the end of the study, most likely because of a delayed maturation of the prostate. This study shows that the maturation of the male genital tract is a progressive process. (ABSTRACT TRUNCATED AT 250 WORDS)

Puberty in the male chimpanzee: time-related variations in luteinizing hormone, follicle-stimulating hormone, and testosterone.

The onset of pubertal testicular growth (Po) occurred in 12 out of 20 male chimpanzees surveyed monthly for at least 3.7 yr. When animals were synchronized according to Po, the mean weight gain was found to be higher before than after Po, and testicular volume started to rise immediately after Po. The earlier significant hormonal events were a rapid rise in LH and a slight testosterone increase occurring 6 mo before Po. Thereafter, the levels of LH remained elevated while testosterone continued to rise in parallel with the testicular volume. FSH levels increased suddenly at Po, 6 mo after the LH increase. FSH remained elevated for only 9 mo, then dropped to prepubertal levels. The dissociation between onsets of pubertal increases in LH and FSH secretions suggests that the complete reawakening of the hypothalamic-pituitary unit lasts several months. The secondary drop of FSH, occurring at the time of spermarche, may be induced by factor(s) secreted by the testis.

Isolation and partial characterization of an HIV-related virus occurring naturally in chimpanzees in Gabon.

Two cases of wild-born chimpanzees which were positive for HIV-1 antibodies were observed in Gabon. These animals were never experimentally exposed to HIV-1 and had no history of inoculation with human blood products. A retrovirus was isolated from one of these chimpanzees. Several of the viral proteins from this virus, designated SIVcpz-GAB-1 (simian immunodeficiency virus from chimpanzee), differed in molecular weight from the known corresponding HIV/SIV proteins. The major gag protein of SIVcpz migrated on SDS-PAGE with a relative molecular mass of 25.5 and the outer membrane proteins were 110, 155 and 185 kD, respectively. SIVcpz did not induce severe cytopathic effects in human and chimpanzee lymphocytes. Antigenically, SIVcpz seems to be closer to HIV-1 than to HIV-2 and the other SIVs. Nucleic acid hybridization experiments appear to indicate that the virus is different from HIV-1 and HIV-2.

Sequence of a novel simian immunodeficiency virus from a wild-caught African mandrill.

Since the isolation of an HIV-2-related virus from captive macaques (SIVMAC), the origin of human immunodeficiency viruses, a much debated subject, has been attributed to monkeys. The sequence of SIVAGM, which is derived from a naturally infected African green monkey, shows equal relatedness to HIV-1 and HIV-2, suggesting that the derivation of these viruses from SIVAGM is unlikely. Recent sequence analysis of SIV from a captive sooty mangabey (SIVMAC), however, shows its close relatedness to HIV-2 and SIVMAC, indicating a possible origin of HIV-2 and SIVMAC from SIVSM (refs 4, 7, 9). We report here the sequence of a novel simian lentivirus, SIVMND, isolated from a wild-caught mandrill in Africa. It is distinct from the three other main groups, HIV-1, HIV-2/SIVMAC/SIVSM and SIVAGM, and therefore represents a fourth main group of primate lentiviruses. Phylogenetic analysis indicates that these four main virus groups might have diverged from a common ancestor at about the same time, long before the spread of AIDS in humans.

Influence of ejaculation frequency on semen characteristics in chimpanzees (Pan troglodytes).

Semen samples were obtained by masturbation from 6 chimpanzees and the spontaneously liquefied fraction and the remaining coagulum were studied separately. When semen was collected once or twice a week, large intra-individual variations were observed for all measures. The liquefied fraction represented 26.5 +/- 3.2% (weighted mean +/- s.d.) of the total ejaculate but contained 51.3 +/- 3.8% of all emitted spermatozoa. Fructose concentration was higher in the coagulum than in the liquefied fraction (29.3 +/- 3.0 mumol/ml vs 12.0 +/- 2.7 mumol/ml, P less than 0.001) whereas acid phosphatase was less concentrated in the coagulum than in the liquefied fraction (3.5 +/- 0.3 x 10(3) IU/ml vs 13.0 +/- 0.9 x 10(3) IU/ml, P less than 0.001). L-Carnitine and citrate concentrations did not differ between the two fractions of the ejaculate. When semen collection was repeated every hour for 5 h, the ejaculate volume increased from 2.6 +/- 0.7 to 4.7 +/- 0.6 ml (P less than 0.001), whereas total sperm count decreased from 1278 +/- 872 x 10(6) to 587 +/- 329 x 10(6) (P less than 0.05) between the 1st and the 6th ejaculate. In the spontaneously liquefied fraction, the sperm count decreased from 984 to 369 x 10(6). The 6 successive ejaculates gave a total of 20.2 +/- 7.6 ml and 4278 +/- 2884 x 10(6) spermatozoa. The increase of the ejaculate volume was essentially due to an increase of the volume of the coagulum which closely correlated with total amount of fructose (from seminal vesicles) (r = 0.913, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Isolation and characterization of simian immunodeficiency virus from mandrills in Africa and its relationship to other human and simian immunodeficiency viruses.

Two isolates of simian retrovirus related to the human immunodeficiency virus (HIV) were obtained from apparently healthy mandrills, Papio (Mandrillus) sphinx, in western equatorial Africa. This virus, designated SIVMND (simian immunodeficiency virus from mandrills), appeared morphologically similar to HIV by electron microscopy, showed Mg2+-dependent reverse transcriptase activity, and induced cytopathic effect in human CD4-positive cells. Western blotting (immunoblotting) analyses revealed that the gag and pol products of SIVMND showed cross-reactivity with those of known HIVs and SIVs. Molecular clones covering full-length viral DNA were obtained from closed circular extrachromosomal DNA of SIVMND-infected cells. By clone-on-clone hybridization with known retroviruses of the HIV and SIV groups, SIVMND showed similar cross-hybridization with HIV-1, HIV-2, SIVAGM (African green monkey-derived SIV), and SIVMAC (rhesus macaque-derived SIV) in the gag and pol regions only at low stringency but not at high stringency, a result indicating that SIVMND is a new member of the HIV-SIV group. The existence of distinct SIVs in different monkey species suggest that recent interspecies transfer of HIV-SIV is unlikely in nature.

Antifilarial activity of CGP 20,376 in chimpanzees (Pan t. troglodytes) naturally infected with Dipetalonema vanhoofi.

CGP 20,376, a benzthiazole and new antifilarial agent, was investigated at CIRMF in eight wild born chimpanzees naturally infected with Dipetalonema vanhoofi. Single oral doses (3.75, 7.5, 11 and 15 mg/kg) were administered. Drug levels during the first hour after administration were assessed in seven chimpanzees at 10 minute intervals in the blood. Levels of unchanged drug (CGP 20,376) were higher than those of its metabolite (CGP 20,308). However, there was considerable variation between individuals, although the results for each animal were consistent. Because of investigational limitations a complete drug profile could not be established. Unsheathed microfilariae of D. vanhoofi were monitored during the first hour following drug administration in seven chimpanzees. In five the microfilaraemia dropped to low counts within 10 minutes and remained below the initial values for the next 50 minutes while in two other chimpanzees it showed a more irregular reduction. Periodic microfilarial counts over the next 20 months, at roughly 30 day intervals, showed that three chimpanzees, treated with 7.5, 11 and 15 mg/kg respectively, remained free of circulating microfilariae from Day 1 to Day 600, the chimpanzee treated with 3.75 mg/kg remained microfilaremic and, in three chimpanzees low numbers of microfilariae reappeared within one year, whereas in the remaining ape they reappeared after one year. No major clinical adverse effects were observed, but liver function tests showed mild reversible changes at the 11 and 15 mg/kg doses. CGP 20,376 was therefore microfilaricidal, except for the lowest dose, and it was possibly macrofilaricidal in those chimpanzees which remained free of microfilariae for 600 days. Clinically CGP 20,376 was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellular and biochemical characteristics of semen obtained from pubertal chimpanzees by masturbation.

Semen characteristics were studied in 6 wild-born chimpanzees with dental ages ranging approximately from 6 to 12 years. The animals formed 2 groups, early pubertal (EP, N = 3, 6-9 years) and late pubertal (LP, N = 3, 11-12 years). Mean body weight, testicular volume and serum androgen concentration were significantly lower in Group EP (32.2 +/- 1.6 kg, 34.0 +/- 7.7 cm3, 2.1 +/- 0.1 ng/ml) than in Group LP (55.7 +/- 5.7 kg, P less than 0.01; 100.5 +/- 11.9 cm3, P less than 0.01; 3.6 +/- 0.7 ng/ml, P less than 0.05). Ejaculates were obtained by masturbation in all subjects. The mean ejaculate volume was lower in Group EP (0.56 +/- 0.20 ml) than in Group LP (3.77 +/- 0.73 ml, P less than 0.01). In Group EP, 2 animals were azoospermic while the third produced semen with means of 57.1 x 10(6) spermatozoa per ml, 20% motility and 40% vitality. These values were low when compared with the mean values of Group LP (376 x 10(6) spermatozoa per ml, 67% motility and 78% vitality). Mean total sperm count was correlated with testicular volume (r = 0.84) and serum androgen concentration (r = 0.96). The mean concentrations of L-carnitine, fructose, citrate and acid phosphatase for the two groups were not significantly different; but, related to the differences in ejaculate volumes, their total amounts in total ejaculate were lower in Group EP than in Group LP. These results suggest that, in chimpanzees, mechanisms of seminal plasma production and ejaculation are functional early in the reproductive life and that the emission of spermatozoa occurs later.

Human T-cell leukemia virus type I isolates from Gabon and Ghana: comparative analysis of proviral genomes.

Two isolates of human T-cell leukemia virus type I (HTLV-I) were obtained from lymphocyte cultures of a healthy carrier in Gabon and another in Ghana. Their proviruses were analyzed by Southern blot hybridization and compared with prototypical HTLV-I isolated in Japan and the United States. The provirus genomes of both strains were highly homologous to the prototype HTLV-I along the whole viral genome. The restriction endonuclease sites of the Ghanian isolate were almost identical with those of the prototype HTLV-I, but 10 of 26 sites of the Gabonese isolate were different from those of the prototype. Furthermore, the restriction map of the Gabonese isolate resembled those of a simian T-cell leukemia virus (STLV-I) isolated from a chimpanzee from Sierra Leone and a variant of HTLV-I from Zaire (HTLV-Ib) more closely than those of any other known HTLV-I. These results indicated the existence of some unique strains of HTLV-I transmitted among African people, and the importance of clarifying the origin and transmission of HTLV group viruses.

Hormones and behavior of prepubertal and peripubertal chimpanzees.

Twenty-one chimpanzees ranging in age from 2.9 to 9.2 years at the midpoint of a study consisting of five 4-week blocks were studied behaviorally in four groups of five or six animals per group, balanced for age and sex. Blood samples for radioimmunoassay of follicle-stimulating hormone (FSH), luteinizing hormone, 17 beta-estradiol, testosterone, dehydroepiandrosterone (DHA), DHA sulfate (DHAS), and cortisol were obtained once each 4-week block. Sex differences were found only in the categories of play duration and initiative and genital inspection, all of which were greater for the males. Several categories (6) of play and other affiliative behaviors were negatively correlated with age and/or body weight for the males, whereas fewer of those categories (2) were so correlated in the females. Hierarchical behavior, genital inspection, solitary behavior other than play, and autogrooming were all positively correlated with age and/or body weight for the males, and only autogrooming for the females. FSH and testosterone levels and testicular volume were positively correlated with age and body weight in the males, whereas for the females cortisol was negatively correlated with body weight and only FSH and the ratios of DHA and DHAS to cortisol were positively correlated with age and/or body weight. Most of the behaviors that were significantly correlated with age and body weight for the males were also correlated in the same direction with FSH and testosterone levels and testicular volume, but not with DHA or DHAS levels. The data are consistent with the view that testosterone, but not the adrenal androgens DHA and DHAS, contributed to the behavioral development of the males. There were few significant correlations between hormones and behavior for the females and interpretation is not clear. The absence of age-related increases in DHA and DHAS of both the males and females, in contrast to the pattern of FSH (and testosterone for the males), supports the growing consensus that adrenarche and puberty are independent developmental processes. The absence of any strong correlations between behavior and levels of the adrenal androgens in either the males or females suggests that adrenarche per se is not a significant event in the behavioral development of chimpanzees.

Renin angiotensin aldosterone axis, including aldosterone binding globulin and blood pressure in three species of nonhuman primates.

Variables of renin-angiotensin-aldosterone axis with inclusion of protein binding to specific plasma globulin (ABG), plasma cortisol, and the blood pressure (BP) were measured in 24 chimpanzees, 4 gorillas, and 16 cynomolgus monkeys. ABG activity was readily detected in plasma from the primates. In chimpanzees and gorillas, all the variables under baseline conditions were similar to those in humans. In cynomolgus (Macaca fascicularis), both the ABG binding capacity for aldosterone and the diastolic or systolic BP were significantly higher (p less than 0.001 and p less than 0.01 respectively) than in chimpanzees and gorillas.

Plasma dehydroepiandrosterone, its sulfate, testosterone and FSH during puberty of African children in Gabon.

Plasma levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), testosterone (T) and follicle stimulating hormone (FSH) were measured by radioimmunoassay in 111 schoolboys and 95 schoolgirls from 7 to 18 years. 68 male and 55 female adults aged from 19 to 25 were also investigated. Results are expressed as the mean +/- SD, DHEA was the first hormone to vary showing a significant mean increase between the 10 and 11 year age groups of both boys and girls. Higher levels were observed in the age 12 group (boys 164.70 +/- 60.74; girls 256.60 +/- 145.40 ng/dl) but were followed by a significant decrease in both 13 year old groups. Similar increases followed by decreases were also noted for DHEAS, although the increase started between 11 and 12 years and reached a maximum at 13. An abrupt increase in FSH levels between 11 and 12 years followed by a plateau through 15-18 years, was observed for boys and girls. As expected, T levels increasing significantly in boys with the initial rise between 11 and 12 and a climb through to the 15-18 age group. Our results suggest a late plasma DHEAS secretion with adult levels attained after age 19. Menarche was also found to be late.

Hormone responses to clomiphene citrate in young chimpanzees.

The responses of gonadotropin and gonadal steroids to the administration of clomiphene citrate were studied in male and female chimpanzees, aged 3.6 to 9.9 years. Follicle-stimulating hormone (FSH) was significantly reduced after treatment in the prepubertal females (n = 4) and in early pubertal males (n = 2) but not in prepubertal males (n = 5). FSH was unchanged or increased in early pubertal females (n = 2) and late pubertal males (n = 2). There was no consistent response to treatment with clomiphene citrate by luteinizing hormone (LH) in either males or females, nor by 17 beta-estradiol in the females. Testosterone levels were reduced in the early pubertal males only. These results support the hypothesis that negative feedback by gonadal steroids is operative in prepubertal chimpanzees and that puberty is accompanied by a reduction in the sensitivity to such feedback.

Spontaneous malformations in squirrel monkey [Saimiri sciureus] fetuses with emphasis on cleft lip and palate.

Gross examination of a group of surviving and nonsurviving squirrel monkeys has revealed a high incidence of cleft lip and cleft primary palate defects with an associated anophthalmia. These defects, as well as single incidences of diaphragmatic aplasia, scoliosis, internal hydrocephalus, and funnel chest, are noted or described and discussed with reference to sex and parentage.

Composition of lemur milk.

The average composition of 8 samples of milk from Lemur catta, L. fulvus, L. macaco and a hybrid lemur was (in g/100 mt): lipids, 2.3; protein, 2.7; lactose, 6.4; and ash, 0.35. The fatty acids and major minerals were also quantified. The results did not support classification of L. fulvus and L. macao within the same species.