Ectopic pregnancies associated with low dose progestagen-releasing IUDs

Dimethyl-polysiloxane capsules containing pure progestagens were attached to Tatum's T IUDs and tested in 594 fertile women for contraceptive performance. The control group was represented by 71 women who received identical devices containing barium sulphate instead of steroid and 100 women who received a Copper T-200. The progestagens and the doses tested were megestrol acetate (4.8, 19.2, 26 and 32 micrograms/day; levonorgestrel (2.1, 3.4 and 8.5 micrograms/day); norethindrone (18 micrograms/day); R2323 (28.6 and 45 micrograms/day); and norgestrienone (26 micrograms/day). Twelve pregnancies were diagnosed during 5201 woman-months of exposure accumulated within the first year of use among users of the steroid-bearing IUDs. Five of these were ectopic gestations. Ten pregnancies, all uterine, were detected during 1701 woman-months of exposure in the control group. Intrauterine delivery of progestagens by means of a carrier IUD is effective in decreasing the pregnancy rate but it might effect postovulatory events in a way which increases the rate of tubal implantation. Because of this property, progestagen-releasing IUDs should be limited to doses that assure maximal effectiveness to avoid increasing the risk of ectopic pregnancy.     

Urinary kallikrein excretion in pregnant adrenalectomized rats

The mechanisms responsible for the increase of the urinary kallikrein activity (UKA) during pregnancy is still unknown. Since aldosterone has been described as one of the stimulatory factor of UKA, and this hormone is considerably elevated in normal pregnancy it is feasible to postulate that it might be involved in the process. A preliminary approach to solve the role of the mineralocorticoid was to investigate the effect of the adrenalectomy upon UKA, of pregnant rats. UKA activity and blood pressure (BP) were measured at weekly intervals in four groups of rats: pregnant-adrenalectomized (P-ADX); pregnant-sham operated (P-C); non pregnant-adrenalectomized (NP-ADX) and non pregnant-sham operated (NP-C). In addition serum aldosterone levels in pregnant rats were determined. All the groups were maintained in similar conditions drinking 1% NaCl solution. The increase in UKA was not detected in P-C, as observed in normal pregnant rats drinking tap water, indicating that a high NaCl intake prevents the rise in UKA during gestation. However, P-C rats had higher UKA than P-ADX on day 14 of pregnancy (p < 0,05). The lowest level of UKA was found in NP-ADX. In NP-C and NP-ADX BP rose progressively throughout the experiment. BP in P-ADX rats during pregnancy and on day 7 of post partum was significantly lower than in P-C rats (p < 0,01-0,02) but in both pregnant groups it decreased significantly before parturition (p < 0,02) increasing at post-partum. Serum aldosterone levels on days 14 ans 21 of gestation, showed higher values in P-C than in P-ADX (p < 0,02-0,005). The results provide support to the assumption that adrenal gland has a regulatory action on UKA during pregnancy and that aldosterone can be one of the main factors involved.     

Effect of intrauterine insemination with spermatozoa or foreign protein on the mechanism of action of oestradiol in the rat oviduct

Previously, we showed that oestradiol accelerates oviductal egg transport through a non-genomic action involving oviductal protein phosphorylation in non-mated rats, and through a genomic action in mated rats. Thus, sensory stimulation, seminal fluid or sperm cells may be the source of signals that switch the mechanism of action of oestradiol in the oviduct to a genomic pathway. The present study examined the ability of spermatozoa to switch the mode of action of oestradiol in the absence of the sensory stimulation and seminal fluid provided by mating. Pro-oestrous rats were inseminated in each uterine horn with epididymal spermatozoa and 12 h later were injected subcutaneously with oestradiol and intrabursally with the mRNA synthesis inhibitor alpha-amanitin. The number of eggs in the oviduct, assessed 24 h later, showed that alpha-amanitin blocked the oestradiol-induced egg transport acceleration, indicating that the interaction of spermatozoa with the genital tract shifts the action of oestradiol from non-genomic to genomic. Other rats were inseminated with live or dead spermatozoa and then treated with the protein kinase inhibitor H-89, and oestradiol. Treatment with H-89 did not block the oestradiol-induced acceleration of egg transport in these rats, although dead spermatozoa did not enter the oviduct, indicating that the mere presence of spermatozoa in the uterus abrogated the non-genomic action of oestradiol in the oviduct. Treatment with H-89 also failed to prevent the acceleration of oviductal egg transport induced by oestradiol in rats inseminated with hamster spermatozoa or with BSA, whereas in rats inseminated with their own serum (autologous proteins), H-89 was able to prevent the effect of oestradiol. This finding reveals that the effect of insemination on the mode of action of oestradiol is neither species-nor sperm-specific and it is produced by foreign organic material. It can be concluded that the presence of spermatozoa or foreign protein in the uterus is one of the components of mating that is capable of switching the action of oestradiol in the oviduct from a non-genomic to a genomic mode.