Summary. Melatonin was administered intravaginally in Silastic tubing to adult and prepubertal ewes. In Exp. 1, ewe lambs (born early March) were given intravaginal melatonin implants at a mean age (±s.e.m.) of 7·5 ± 0·1 weeks (Group E, N = 10) or 19·4 ± 0·2 weeks (Group L, N = 10). The third group (Group C, N = 10) received empty implants. In Exp. 2 mature ewes were given implants on 13 May (Group E, N = 10)or 18 July (Group L, N = 10)or received empty implants (Group C, N = 10) on one of these two dates. Blood samples were taken twice weekly for progesterone assay. In Exp. 1 the mean age ( ± s.e.m.) at puberty (progesterone > 2 nmol/l for two consecutive samples) was 35·4 ± 0·8 weeks. Puberty was advanced by 5·2 weeks in Group L lambs, occurring at a mean age of 30·2 ± 0·7 weeks (P < 0·001). In Group E lambs the timing of puberty was unaltered, occurring at a mean age of 34·8 ± 0·6 weeks. Mature ewes in Group L (Exp. 2) showed increased incidence of ovarian activity (9/10 ewes cycling by 26 September) compared with the control ewes (1/10) (P < 0·001), but there was no effect in Group E ewes (3/10). The results demonstrate that continuous melatonin administration to adult and prepubertal ewes can mimic the effect of short days in terms of the reproductive response, and that the present and previous exposure to melatonin is critical in determining the response.
R. Nowak and R. G. Rodway
Summary. Adult anoestrous ewes (N = 30) were given intravaginal Silastic implants containing melatonin or empty implants (N = 7) during mid-anoestrus (4 July). Implants were removed 16 days later (Group 1), 36 days later (Group 2) or 93 days later (Group 3). Blood samples were taken twice weekly for progesterone assay to monitor onset of ovarian activity. The percentage of ewes in each group showing early onset of ovarian cyclicity was significantly correlated with length of exposure to melatonin.
A G Braundmeier, A T Fazleabas, and R A Nowak
Extracellular matrix metalloproteinase inducer (EMMPRIN; BSG) regulates tissue remodeling through matrix metalloproteinases (MMPs). In human and non-human primates, endometrial remodeling is important for menstruation and the pathogenesis of endometriosis. We hypothesized that as in humans, BSG and MMPs are expressed in the endometrium of cycling baboons, and their expression is hormonally regulated by ovarian hormones, but endometriosis disrupts this regulation. BSG expression was evaluated in the baboon endometrium by q-PCR and immunohistochemistry. In the endometrium of control cycling animals, BSG mRNA levels were highest in late secretory stage tissue. BSG protein localized to glandular epithelial cells during the proliferative phase; whereas, secretory stage tissues expressed BSG in glandular and luminal epithelia with weak stromal staining. Several MMPs were differentially expressed throughout the menstrual cycle with the highest levels found during menstruation. In ovariectomized animals, BSG endometrial mRNA levels were highest with treatment of both estrogen and progesterone than that with only estrogen. Estrogen alone resulted in BSG protein localization primarily in the endometrial glandular epithelia, while estrogen and progesterone treatment displayed BSG protein localization in both the glandular and stromal cells. Exogenous hormone treatment resulted in differential expression patterns of all MMPs compared with the control cycling animals. In the eutopic endometrium of endometriotic animals, BSG mRNA levels and protein were elevated early but decreased later in disease progression. Endometriosis elevated the expression of all MMPs except MMP7 compared with the control animals. In baboons, BSG and MMP endometrial expression is regulated by both ovarian hormones, and their expression patterns are dysregulated in endometriotic animals.
R Nowak, RH Porter, F Levy, P Orgeur, and B Schaal
The defining characteristic of mammals is that females nurse and care for their young; without this, the neonate has no chance to survive. Studies on wild and domestic species show that the neonatal period is the most critical step in the lifetime of a mammal. This review compares three well-studied species (the rabbit, pig and sheep) that differ in their parental strategies and in the problems that neonates have to overcome. As a general trend, mother-young interactions vary according to the maturity of the newborn, and the size of the litter. Neonatal survival relies to a great extent on an environment that is ecologically appropriate for the developmental stage of the neonate, and on optimum interactions with the mother. Adaptive maternal care supposes that the mother provides the basic needs of the neonate: warmth (in pigs and rabbits) or shelter, food, water and immunological protection (via colostrum) and, in some instances, protection from predators and other conspecifics. A major risk facing all neonates, other than the birth process itself, is inadequate colostrum intake owing to delayed suckling or competition with siblings, which leads to starvation, hypothermia or even crushing, as has been observed in pigs.
L. K. Ritzhaupt, R. A. Nowak, F. O. Calvo, I. M. Khan, and J. M. Bahr
Summary. Basal adenylate cyclase values for corpora lutea (CL) removed from cyclic gilts on Days 3, 8, 13 and 18 were 178 ± 61, 450 ± 46, 220 ± 25 and 208 ± 18 pmol cAMP formed/min/mg protein, respectively. Basal activity was significantly elevated on Day 8 (P < 0·001). LH-stimulatable adenylate cyclase values for CL from Days 3, 8, 13 and 18 were 242 ± 83, 598 ± 84, 261 ± 27 and 205 ± 17 pmol cAMP formed/min/mg protein respectively. Serum progesterone concentrations of 12 gilts bled every 2 days through one complete oestrous cycle ranged from 1·1 to 26·9 ng/ml with highest values between Days 8 and 12. The decline in serum progesterone concentrations was coincident with the decrease in basal adenylate cyclase activity. There was no LH-stimulatable adenylate cyclase activity present in the CL at the specific times of the oestrous cycle examined. We conclude that progesterone secretion by the pig CL is apparently dependent on basal activity of adenylate cyclase.
R. A. Nowak, M.-W. Wang, M. H. Hamon, D. J. Lamb, D. W. Bullock, and R. B. Heap
Summary. Anti-progesterone monoclonal antibody, injected into mice 32 h after mating at a dose that blocks the establishment of pregnancy, produced a significant reduction in the concentration of progesterone in the ovary and uterus within 6 h after treatment. Uterine concentrations remained lower in treated compared with control animals for at least 24 h after injection. There was an associated transient increase in plasma LH and FSH concentrations, but there was no change in plasma prolactin values. The percentage of total progesterone in the circulation that was unbound was reduced after treatment, but the concentration of unbound progesterone was increased. Studies of antibody binding of steroid in the presence of uterine progesterone receptor protein showed that there was a stoichiometric relationship in the distribution of ligand between the two binders. The present findings suggest that the effects of passive immunization against progesterone are associated with perturbation of tissue concentrations of steroid in the target organ as a result of high antibody concentrations in the circulation.
Keywords: progesterone; immunization; pregnancy; uterus; ovary; mouse