An adequate inter-birth interval is of great importance because it enables a mother to recover her physical and emotional strength between pregnancies and confers upon the child advantages of better health and development (Morley, 1977). Breast feeding is the naturally evolved method of ensuring an adequate inter-birth interval but the contraceptive effect of breast feeding has been largely dismissed in developed countries on the grounds that it is an unreliable method of family planning for individual mothers (Kamal et al., 1969). The use of artificial contraception varies very widely in different countries, being much higher in developed nations than in the poorer developing countries (Text-fig. 1). Where the use of artificial contraceptives is low, breast feeding is the most widely used method of birth spacing and assumes major demographic importance. It is important, therefore, that the factors controlling lactational infertility should be understood so that guidelines can be developed which
P. W. Howie and A. S. McNeilly
J M Young and A S McNeilly
Theca cells function in a diverse range of necessary roles during folliculogenesis; to synthesize androgens, provide crosstalk with granulosa cells and oocytes during development, and provide structural support of the growing follicle as it progresses through the developmental stages to produce a mature and fertilizable oocyte. Thecal cells are thought to be recruited from surrounding stromal tissue by factors secreted from an activated primary follicle. The precise origin and identity of these recruiting factors are currently not clear, but it appears that thecal recruitment and/or differentiation involves not just one signal, but a complex and tightly controlled combination of multiple factors. It is clear that thecal cells are fundamental for follicular growth, providing all the androgens required by the developing follicle(s) for conversion into estrogens by the granulosa cells. Their function is enabled through the establishment of a vascular system providing communication with the pituitary axis throughout the reproductive cycle, and delivering essential nutrients to these highly active cells. During development, the majority of follicles undergo atresia, and the theca cells are often the final follicular cell type to die. For those follicles that do ovulate, the theca cells then undergo hormone-dependent differentiation into luteinized thecal cells of the corpus luteum. While the theca is an essential component of follicle development and ovulation, we do not yet fully understand the control of recruitment and function of theca cells, an important consideration since their function appears to be altered in certain causes of infertility.
K. M. Henderson, A. S. McNeilly and I. A. Swanston
Summary. The concentrations of LH, FSH and prolactin, and oestradiol-17β, androstenedione, testosterone and progesterone were measured in follicular fluid from small, medium and large bovine follicles. As follicle size increased, there was a significant increase in median fluid concentrations of prolactin (2-fold) and oestradiol-17β (14-fold) and a significant decrease in concentrations of LH (to 73%), androstenedione (to 30%) and testosterone (to 10%). There was no relationship between follicle size and fluid concentrations of FSH or progesterone, or between fluid concentrations of FSH and the relative concentrations of androgen and oestradiol-17β. As follicle size increased there was a significant increase in the proportion of follicles in which follicular fluid concentrations of oestradiol-17β exceeded those of androgen. There was a significant relationship between follicular fluid concentrations of prolactin and progesterone; as fluid prolactin concentrations increased, the maximum concentration of progesterone observed decreased.
A. S. McNeilly, J. A. Jonassen and H. M. Fraser
Summary. Active immunization of 6 Damline ewes against LHRH during seasonal anoestrus resulted in an inhibition of ovarian cyclicity throughout 2 subsequent breeding seasons. This was associated with a significant suppression of plasma LH and FSH concentrations but no significant effect on prolactin. The ovaries of LHRH-immunized ewes 30 months after primary immunization contained no follicles > 2·5 mm in diameter and a greater proportion of follicles between 1 and 2 mm were atretic than in control ewes (N = 8). In-vitro production of testosterone and androstenedione were similar in follicles 1–2 mm in both control and LHRH-immunized ewes (N = 6) and all had little or no ability to secrete oestradiol. However, basal and hCG-stimulated progesterone secretion was suppressed in the follicles from LHRH-immunized ewes. These results show that follicular development beyond 2·5 mm in the ewe is dependent on adequate stimulation by both LH and FSH.
G. A. Lincoln, A. S. McNeilly and C. L. Cameron
Summary. Six adult Soay rams were preconditioned to an artificial lighting regimen of alternating 4-month periods of long (16L:8D) and short days (8L:16D) for at least 10 months before blood samples were collected at hourly intervals for 24 h at various times. The abrupt change from long to short days resulted in a progressive decrease in plasma levels of prolactin, while that from short to long days had the reverse effect; the first response to the light changes was rapid, beginning within 6 days. During the periods of high secretion there was a 24-h cycle in plasma prolactin concentrations, with a peak in both the early dark and early light phases of each day. Changes in the relative magnitude of these peaks were observed in relation to the long-term alteration in prolactin secretion. Plasma levels of FSH were also measured and a close inverse relationship between gonadotrophin and prolactin secretion was observed.
G. A. Lincoln, C. E. Lincoln and A. S. McNeilly
Summary. Seasonal cycles in testicular activity in rams were monitored in groups of wild (mouflon), feral (Soay) and domesticated breeds of sheep (Shetland, Blackface, Herdwick, Norfolk, Wiltshire, Portland and Merino) living outdoors near Edinburgh (56°N). The changes in the blood plasma concentrations of FSH, inhibin and testosterone, and the diameter of the testis were measured every half calendar month from 1 to 3 years of age. There were significant differences between breeds in the magnitude and timing of the seasonal reproductive cycle. In the mouflon rams, the seasonal changes were very pronounced with a 6–15-fold increase in the plasma concentrations of FSH, inhibin and testosterone from summer to autumn, and a late peak in testicular diameter in October. In the Soay rams and most of the domesticated breeds, the seasonal increase in the reproductive hormones occurred 1–2 months earlier with the peak in testicular size in September or October. In the two southern breeds (Portland and Merino), the early onset of testicular activity was more extreme with the seasonal maximum in August. In cross-bred rams, produced by mating Soay ewes (highly seasonal breed) with Portland or Merino rams (less seasonal breeds), there was a seasonal reproductive cycle that was intermediate compared to that of the parents. A comparison between all 11 breeds showed a significant correlation between the timing of the seasonal cycle in plasma FSH concentration and testicular diameter (time of peak FSH vs testis, r = 0·95).
The overall results in the rams are consistent with a primary role of FSH in dictating the seasonal cycle in testicular size and the secretion of inhibin. The earlier seasonal onset in the testicular cycle in the southern breeds of domesticated sheep, and the differences from the wild type, are taken to represent the effects of genetic selection for a longer mating season.
Keywords: seasonal breeding; pituitary gland; testis; inhibin; genetic variation; sheep
Jacqueline M. Wallace, A. S. McNeilly and D. T. Baird
Summary. Treatment of Damline ewes with twice daily i.v. injections of bovine follicular fluid during the luteal phase for 10, 6 or 2 days before prostaglandin-induced luteolysis resulted in an increase in ovulation rate. This was associated with a large rebound increase in plasma concentrations of FSH after the last injection of bovine follicular fluid. While conception rate was not affected by bovine follicular fluid treatment, a higher percentage embryonic loss was observed between Days 3 and 34 of pregnancy in the 10-day treatment group only compared to controls. This reflected the increase in ovulation rate above the optimum for embryonic survival in this breed. The present results suggest that the increase in ovulation rate induced by bovine follicular fluid treatment in the luteal phase of the cycle before mating would result in a significant increase in the number of lambs born.
J. Brooks, W. J. Struthers and A. S. McNeilly
Gonadotrophin and inhibin concentrations were measured in anoestrous ewes after acute treatment with either saline, ovine follicular fluid (oFF), GnRH antagonist, or oFF and GnRH antagonist in combination. The increase in mean LH concentrations observed in ewes treated with oFF alone, was not seen in either of the groups treated with GnRH antagonist, in which LH pulsatility was completely inhibited. This result suggests that the LH rebound that follows follicular fluid treatment is GnRH dependent. Blockade of GnRH had no effect on the suppression of FSH seen after follicular fluid injection, indicating that this component of FSH secretion is independent of short-term GnRH input. After this initial suppression, a rebound release of FSH was seen in the group treated with oFF alone. The addition of GnRH antagonist appeared to decrease the rebound, suggesting that this rebound release of FSH may have a GnRH-dependent component. Inhibin concentrations in both oFF-treated groups increased after oFF injection and then declined to pretreatment values. However, a second rise in inhibin concentration, concomitant with the FSH rebound in ewes receiving oFF alone, was seen in the group treated with oFF and GnRH antagonist. As this rise in endogenous inhibin concentration could also act to suppress the rebound release of FSH, it cannot be conclusively proved from this study that GnRH input is required for the generation of the rebound release of FSH after treatment with oFF.
H. M. Fraser, I. J. Clarke and A. S. McNeilly
Summary. Endogenous LH-RH in ewes was inhibited by active immunization or by injection of LH-RH antiserum. Plasma levels of LH and FSH were elevated in 3 ovariectomized control ewes but low in 3 LH-RH immunized ovariectomized ewes. Oestradiol benzoate (50 μg i.m.) caused a marked rise in LH concentrations in control ewes but not in the immunized ewes. In the immunized ewes the low plasma levels of FSH decreased even further 8–36 h after injection of oestrogen, indicating a direct inhibitory action of the steroid on the pituitary. Both groups responded to the oestrogen injection by a rise in plasma levels of prolactin and by exhibiting normal oestrous behaviour.
When the control ewes were again challenged with oestradiol benzoate and, after 10 h, given an i.v. injection of 75 ml antiserum to LH-RH, the LH surge was abolished in one animal and reduced in another. These experiments indicate that the continued presence of LH-RH is necessary for the occurrence of the oestrogen-induced LH surge in the ewe.
Administration of a stimulatory analogue of LH-RH released LH and FSH in control and immunized ewes but the responsiveness to further injections at intervals of 3 h decreased, particularly for FSH.