Trypanosomiasis induces histological testicular degenerative changes leading to suppression of spermatogenesis in goats and laboratory animals. We present evidence associating these changes with trypanosome-induced endocrine dysfunction. Toggenburg goats were infected with approximately 100,000 trypanosomes. They were bled every 2 days, and the plasma testosterone was analyzed by radioimmunoassay. Testes were perfused with and fixed in Bouin's fixative for histological evaluation. The infected plasma samples showed depressed testosterone levels with episodic peaks reduced in both amplitude and frequency. Histological characteristics of the testicular and epididymal tissues revealed aspermic tubules and epididymides and desquamation of the tubular germinal epithelia. These testicular degenerative changes may be partly due to the depressed plasma testosterone levels.

A protein with the capacity to bind [3H] testosterone was prepared from cauda epididymides of 60 dogs. Antibodies against the protein were generated in goats and purified by ammonium sulphate precipitation, column chromatography and tissue adsorption. Passive immunization of male dogs with the purified antibody resulted in disruption of the epithelium of the cauda epididymis, but epithelia of the caput and corpus epididymides remained normal. There was also evidence of considerable testicular damage. It is suggested that the results point to the possibility that specific epididymal proteins could be utilized in the development of immunocontraceptive vaccines for use in fertility control in domestic and wild species.

1. An androgen binding protein(s) has been partially purified from cell plasma membranes of dog epididymides. 2. The protein(s) has a pI of 5.3 and an association constant of (1.13 x 10(9) M-1). 3. Conclusive demonstration of androgen receptors in epididymal plasma membranes would be of significance in understanding epididymal physiology.

The morphogenesis of the foetal membranes of the African cane rat (Thryonomys swinderianus, Temminck) was studied and compared with that of the caviomorphs from South America. Like the guinea pig and chinchilla, implantation in the cane rat is interstitial, amniogenesis is by cavitation, there is very early and complete inversion of yolk sac endoderm, there is a well-developed subplacenta which persists throughout gestation, and the interhaemal membrane is haemomonochorial in nature. The phylogenetic significance of these findings are discussed in the light of long geographical and temporal separation between the continents.

In vitro metabolism of progesterone by hyrax whole blood, erythrocytes, or plasma in the presence or absence of NADPH was investigated. In the presence of NADPH, whole blood metabolized progesterone to 5 alpha-pregnanedione and 5 beta-pregnanedione, but in the absence of NADPH, only 5 beta-pregnanedione was produced. Erythrocytes in the presence and the absence of NADPH produced only 5 beta-pregnanedione. The plasma component of blood metabolized progesterone to give 5 alpha-pregnanedione, but only in the presence of NADPH. These results suggest the presence of two types of steroid reductases found in plasma and erythrocytes. The extent of progesterone metabolism by the blood of animals in different reproductive states is in the order of pregnant females greater than nonpregnant females greater than male.

Changes in plasma cortisol and thyroxine (T4) levels were measured weekly in female goats experimentally infected with Trypanosoma congolense. Values for plasma cortisol (range 10 to 25 nmol litre-1) and T4 (range 65 to 120 nmol litre-1) were within normal ranges in all goats before infection and in control animals throughout the 24 weeks of study. Cortisol/T4 ratios of 0.23 to 0.15 (or 1:4 to 1:7) were obtained. In the infected goats a significant increase in cortisol and decline in T4 were simultaneously observed within one week of the onset of parasitaemia and fever. A peak cortisol/T4 ratio of 2.0 (2:1) was obtained four weeks after infection when cortisol levels rose to 59.0 +/- 8.9 nmol litre-1 and T4 declined to 29.4 +/- 2.2 nmol litre-1. Thereafter the mean levels fluctuated but remained high (over 30 nmol litre-1) for cortisol and low (under 50 nmol litre-1) for T4 up to 18 weeks after infection. Both hormones tended to return to normal levels towards the end of the study. The changes in mean cortisol levels showed a significant inverse correlation with changes in T4 (r = -0.57, P less than 0.001, n = 26). It is suggested that in trypanosomiasis, hypothalamic stress causes increases in plasma cortisol levels and at the same time suppresses the activity of the thyroid gland.

Differences in susceptibility of the Small East African breed of goats to an experimental Trypanosoma congolense infection were investigated. The goats were obtained from different areas of East Africa, Morogoro and Arusha (Tanzania), Imbo and Lambwe Valley (Kenya). Morogoro goats were found to be more tolerant, followed by Arusha, Lambwe Valley and Imbo goats, in that order. The Imbo goats had highest parasitaemia, more severe anaemia, marked weight losses and highest mortality rate. The Morogoro goats showed a milder infection with lower parasitaemia, less severe anaemia, weight losses and lowest mortality rate. The Lambwe Valley and Arusha goats were intermediate to the Morogoro (resistant) and Imbo (susceptible) goats. The significance of these findings in relation to existence of heterogeneity in the Small East African goats is discussed.

Plasma progesterone and 13,14-dihydro-15-keto Prostaglandin F(2alpha) (PGFM) were measured in normal (uninfected) and Trypanosoma congolense -infected adult goats for a period of 121 d, from May to August, during the breeding season in Kenya. Chronic trypanosomiasis rapidly increased the baseline plasma PGFM levels and the occurrence of irregular PGFM peaks in several infected goats. Progesterone luteal levels declined rapidly from the second and subsequent cycles post patency. Estrous cycles also became irregular but predominately shorter (8 to 19 d) before cessation from the second to fourth cycle following infection. The PGFM levels were still high during the acyclic period in all goats when progesterone levels were very low (1.4 to 2.4 nmol/l). The reciprocal increase in peripheral PGFM and decline in progesterone in these goats would suggest, in part, a trypanosome-induced PGF(2alpha) mediated luteolysis, and the possible involvement of prostaglandins in trypanosome-induced infertility in female goats.

Changes in the ovaries, pituitary, thyroid and adrenal glands in Small East African normally cycling female goats chronically infected with Trypanosoma congolense are described. Marked fibrosis of the ovaries, a decrease in the number of primordial and primary follicles and atresia of growing follicles at the tertiary stage resulting in lack of corpora lutea were observed. The pituitary glands revealed reduced degranulation of the basophils and slight hypertrophy of the acidophils. The thyroids were extensively degenerated and atrophied whereas the adrenal cortices were markedly hypertrophied in some regions and atrophied in others. It is concluded that chronic trypanosomiasis causes marked reproductive lesions in females comparable to those previously described in male animals.

Changes in the length of oestrous cycles, plasma progesterone and oestradiol-17 beta levels were monitored for 6 months in Trypanosoma congolense-infected normocyclic small East African goats obtained from three tsetse-endemic areas and one tsetse-free area of East Africa. Irregular oestrous cycles were observed in all infected goats, before cessation at the second cycle post-infection in the more susceptible and fourth cycle in the more resistant goat groups. A significant decline in the progesterone and oestradiol-17 beta parameters were observed. The decline in hormonal values was, however, less in the more resistant than in the susceptible goat groups at least in the first 2 months post-infection. Resumption of the ovarian cycle were observed in few resistant goats after 5 months of the infection. It is concluded that clinical tolerance is correlated with residual fertility, i.e., the greater the tolerance the higher the retention of fertility.

Adult normocyclic female goats experimentally infected with Trypanosoma congolense developed irregular and shorter estrous cycles before complete cessation at the fourth cycle post-infection. This was followed within a month by a decline in the mean plasma progesterone and estradiol-17 beta levels. The peak luteal progesterone as well as pre-ovulatory estradiol-17 beta level declined progressively from the second to the fourth cycle post-infection. The ovaries became atretic with reduced numbers of primordial and primary follicles. The larger follicles became atretic at the tertiary stage with subsequent lack of corpora lutea formation. The rapidity of ovarian dysfunction appeared to be related to the degree of susceptibility of the individual infected goats.

Changes in plasma T4 levels were investigated in prepubertal and adult female goats during the course of an experimental Trypanosoma congolense infection. A significant decline in the T4 levels was observed within 1 week of trypanosome challenge. The levels remained low up to the end of the 7th weeks when prepubertal goats received a trypanocidal treatment, whereafter the values started to rise to normal pre-infection values. The post-infection plasma T4 values in the untreated adult goats did not return to normal except in one resistant goat which recovered naturally after 16 weeks of the infection. The thyroid glands of chronically infected and untreated adult goats revealed marked atrophy, fibrosis and colloidopathy. It is concluded that trypanosomiasis rapidly impairs thyroid gland function in susceptible animals, but these changes can be reversed by early trypanocidal treatment before marked degenerative changes become evident or following self cure in resistant animals.

We have examined the effects of prolactin (PRL) on progesterone (P) and estradiol (E2) synthesis by cells obtained from human corpora lutea of early and midluteal phases. The cells were cultured in the presence or absence of low (200 mIU/l) or high levels (1000 mIU/l) of PRL. Basal P, but not E2 was significantly (P less than 0.05) enhanced by the low level of PRL, whereas the high level of PRL increased P only in midcycle cells during the initial 48 hours of culture. The high PRL dose significantly (P less than 0.05) reduced E2 production in both early and midcycle cells during the initial 48 hours of culture. Both levels of PRL significantly (P less than 0.05) inhibited human chorionic gonadotropin (hCG)-stimulated P and E2 production in early luteal cells. In the midcycle corpora lutea cells, the low dose of PRL enhanced hCG-stimulated P but not E2, whereas the high dose of PRL was inhibitory to both P and E2. The high dose of PRL also inhibited prostaglandin E2 but not 8-bromoadenosine 3':5'-cyclic monophosphate-stimulated P and E2 synthesis. These results demonstrate that PRL has a direct effect on luteal cell steroidogenesis.

Eighty-two subestrous cattle were treated with different doses of cloprostenol through intramuscular (i.m.) and intravulvo-submucosal (i.v.s.m.) injections to study hormonal profile and fertility. The study was divided into two experiments. In Experiment I, 13 cows were treated with one of three doses of cloprostenol (500 μg i.m., 125 and 62.5 μg i.v.s.m.) to measure response of progesterone (P4) and estradiol (E2). P4 decreased abruptly and E2 levels increased from basal levels following injections of the two larger doses of cloprostenol. P4 decreased to<5 nmol/l approximately 72 h after treatment. E2 levels increased to >300 pmol/l 24 h after cloprostenol injections except in cows treated with 62.5 μg dose. Close agreement was observed between P4 profiles and clinical findings following 500 and 125 μg of cloprostenol treatment. In Experiment II, 69 subestrous cows were treated with either 500 μg i.m. or 250, 125 or 62.5 μg i.v.s.m. doses of cloprostenol. The percent of cows in estrus 96 h following treatment were 60, 80, 67.8 and 18%, respectively. A total of 29 cows were artificially inseminated and 41.3% conceived. We concluded that i.v.s.m. injections of cloprostenol at the dosage of 125 μg and above causes luteolysis, induces estrus and establishes fertility in subestrous cattle. The method is economical but time consuming when compared to the intramuscular route.