Reproductive physiology and endocrinology of normal and habitually aborting Angora goats

Abstract

Recurrent abortion of non-infectious or non-organic origin is exceedingly prevalent in many species including man, yet virtually no information on possible metabolic and endocrine causes was available. In order to study the pathogenesis of this form of gestational failure, an experimental flock was constituted which consisted of normal and habitually aborting Angora goats, a species in which the high incidence of abortion constitutes a significant economic problem. The investigation was initially complicated by the fact that at the time of its inception there were no acceptable theories regarding the cause of the initiation of normal parturition. For this reason experimental work on relevant fundamental aspects was included in the study. Comparative studies on normal and aborting goats entailed: (i) Investigations of sexual behavioural patterns and of breeding performance in mature animals, followed by physiological, clinical and pathological observations on mature does, foetuses and kids. (ii) Development of suitable methods for the precise chemical assay of steroid hormone metabolism in goats. The methods used facilitated detailed studies on luteal function, cortisol metabolism and the excretion of oestrogens. (iii) Investigation of the mohair growth rate as well as its fibre characteristics in relation to reproductive capabilities. (iv) Experimental reproduction in normal animals of the aberrations found and the investigation of the significance of such aberrations in causing gestation termination. Gestational failure was more prevalent in the heavier, older type of goats which were found to have enlarged pituitaries and which occasionally exhibited clinical signs of disturbed adrenal function. Animals that had aborted exhibited abnormally short oestrous cycles which appeared to be responsible for a lowered conception rate. Their ovaries contained cystic corpora lutea and displayed excessive follicular growth; experimental studies indicated that these changes were secondary to adrenal hyperplasia. Abortions were most frequent during the early part of the fourth month of gestation, a time which coincided with the most rapid increase in the rate of foetal growth and also with the cessation of placental growth. The condition of the foetus destined to be aborted suggested placental insufficiency; growth was retarded, anaemia was usually present and the concentration of some elements in the liver was abnormally low. Changes noted prior to abortion included excessive or deficient urinary oestrogen excretion, excessive ovarian follicular growth, the sudden onset of maternal adrenal atrophy, accumulation of excessive foetal fluids and degeneration of the placentomes. Control of gestation maintenance by the corpus luteum was confirmed; removal of the corpus luteum from Angora goats at any stage of pregnancy resulted in abortion 40 to 60 hours later. Variations in the level of luteal function during gestation are postulated to be due to a placental lactogen-type hormone secreted by the growing placenta. Peripheral plasma levels of progesterone tended to be higher than usual in pregnant aborters, but were depressed shortly prior to abortion in only some individuals. Studies on ovarian secretion rates suggested that this reduction was partly due to a lowered adrenal contribution, which may be expected in view of an observed concurrent adrenal atrophy. Signs of impending abortion were, however, evident while luteal function was still quite normal. The markedly aberrant oestrogen excretion rate of aborters could only be ascribed to an abnormal supply of steroid precursors resulting from altered metabolism in the maternal adrenal glands. Newborn kids destined to perpetuate the abortion defect tended to be heavier than normal and had finer birthcoats. The quantity of mohair produced by the young animal born from aborter stock was exceptional and the young males produced 30 per cent more than usual. Adrenal function in young high-producing aborter stock was lower than usual. However, established regular aborters had enlarged adrenal cortices and produced smaller quantities of finer mohair. Such findings are consistent with experimental results obtained with other species, the results demonstrating that corticosteroids inhibit the rate of hair growth and the fibre diameter. Evidence is presented which suggests that the adrenal enlargement found in aborters is an adaptive response favouring the foetus at the expense of hair production characteristics; aborter does which could maintain a higher level of adrenal function throughout gestation carried their foetuses successfully to term. Experimental administration of small doses of corticosteroids to goats during pregnancy prolonged gestation by several days, a situation which resembled successfully adapted aborter does. Dose-related prolongation of gestation was also obtained when small amounts of corticosteroid were administered to the sheep or goat foetus, but slightly higher dosages lead to rapid expulsion of the foetus. When administered maternally to sheep, these steroids caused a moderate reduction of placental progesterone synthesis. However, the same dosage rate given to the foetus caused a more drastic progesterone block, rapidly followed by expulsion of the foetus. Adrenalectomy of the foetus caused indefinite prolongation of gestation in sheep, but not in goats. The investigations have contributed to the concept that normal birth is initiated by the foetal hypothalamus-pituitary-adrenal axis; when the hypothalamus is adequately sensitive to ensure viability of the foetus, it responds to the usual prenatal deterioration of the foetal nutritional environment by stimulating the foetal adrenal glands and the elevated steroid secretions have effects on the foetoplacental unit, resulting in the initiation of parturition, possibly by means of blocking both the production and the action of progesterone. The cause of abortion in Angora goats appears to be intimately related to a high metabolic priority for hair growth, artificially induced by intensive selection and inbreeding. An abnormally low level of adrenal function, coupled with some qualitative changes in adrenal steroid biosynthesis seems to be the responsible mechanism. Physiological adaptation involves adrenal hyperplasia in order to assist the transfer of maternal nutrients to the foetus. Abortion is a consequence of the failure of this mechanism.