The mechanism of the contraceptive effect of an intrauterine silk thread in the rat uterus is not clearly understood. It has been suggested that such a device may act by releasing into the intraluminal fluid a blastotoxic substance which destroys the blastocyst before implantation (Batta & Chaudhury 1968a, b; Marston & Kelly, 1969; De Boer, Anderson & Melampy, 1970; Eckstein, 1970). In the present study the concentrations of amino acids in the intraluminal fluid of a horn containing a silk thread were compared to those in fluid from uteri without any devices.
M. Roy Chaudhury and R. R. Chaudhury
ASHA SETHI and R. R. CHAUDHURY
R. R. CHAUDHURY and ASHA SETHI
Changes in the pattern of cell division in the rat uterus with an intra-uterine silk thread suture in one horn were studied during the first 5 days of pregnancy.
There was no appreciable difference between the mitotic counts in the two horns on Days 1 to 4 of pregnancy, except that there was an increase in the luminal epithelial mitotic count on Day 4 of pregnancy in the horn with the device.
There was a marked difference in the luminal mitotic count between the two horns on Days 4 and 5 of pregnancy. While the mean mitotic count was 1·7 in the control horn on Day 5, it was 421 in the horn with the device. The diminution in the mitotic count seen on Day 5 of pregnancy in the control horn was not present in the horn with the device. It is possible that the effect of endogenous progesterone in causing diminished mitosis in the lumen was prevented by the presence of an IUD.
S. K. BATTA and R. R. CHAUDHURY
In rats provided with a surgically created anastomosis between the two uterine horns and subsequently mated, implantation occurs with great regularity. Implantation sites were seen in twenty-six out of the thirty-two rats examined at laparotomy on Day 10 of pregnancy.
In rats with such an anastomosis and unilaterally ovariectomized, implantation occurred in both uterine horns. There was evidence of implantation in nine out of twelve rats in the left uterine horn, even though the left ovary had been removed, indicating that the anastomosis was patent.
Out of fifteen successfully mated rats with a connection between the two uterine horns and a silk suture in the lumen of the left uterine horn, only one rat showed evidence of implantation in the left uterine horn on Day 10 of pregnancy. There were no signs of implantation sites in the right horn in any animal in this series. The results demonstrated inhibition of implantation in the control horn when an intra-uterine device was placed in the experimental horn in rats with an anastomosis between the two horns. This suggests that the presence of a device in one horn led to the liberation of a substance which passed to the control horn through the surgically created anastomosis and there prevented implantation.
G. P. GARG and R. R. CHAUDHURY
It has been suggested that histamine released by an oestrogen surge at the time of implantation plays an important part in nidation of the fertilized ovum in the rat. These observations were based on findings by Shelesnyak and his co-workers that (a) administration of intraluminal histamine caused an induction of deciduomata, (b) intraluminal administration of histamine antagonists could inhibit deciduomata, (c) intraluminal administration of histamine antagonists could inhibit ovum implantation, and (d) systemic administration of histamine and histamine-releasing agents induced deciduomata (Shelesnyak 1952a, b, c, 1954; Kraicer & Shelesnyak, 1958). These workers also observed a fall in the level of the histamine content of the uterus at the time of implantation. The results of other investigators have, however, not confirmed this hypothesis (Finn & Keen, 1962; Wrenn, Bitman, Cecil & Gilliam, 1964).
S. K. SAKSENA and R. R. CHAUDHURY
One of the aza-analogues, 7,8,9,10-tetrahydro-7-oxo-benzo (c) phenanthridine exhibited an anti-androgenic activity on immature, castrated, male rats. The compound had an interesting anti-androgenic activity as the effect of testosterone-induced gain in weight of the ventral prostate was significantly inhibited by the compound. This compound did not, however, inhibit the androgen-induced weight increase of the seminal vesicle.
S. K. SAKSENA and R. R. CHAUDHURY
Nine azasteroids have been evaluated for antifertility effect in rats when fed orally from Days 1 to 4 of pregnancy at the dose of 10 mg/kg body weight. The compounds 3β-hydroxy-androst-5-ene (16, 17-C)-5-methyl-pyrazole and 1,2,3,4-tetrahydro-N-tosyl-8-methoxy-4-oxo-benzo(b)quinoline inhibited pregnancy at that dose in a significant number of rats.
V. S. MATHUR and R. R. CHAUDHURY
The mechanism by which an intra-uterine device in one horn of the rat uterus prevents implantation in that horn is not known. It has been suggested that histamine has a role to play in the implantation of the fertilized ovum (Shelesnyak, 1952). Shelesnyak, Kraicer & Zeilmaker (1963) have indicated that on the latter part of the 3rd day after successful mating in rats there is an oestrogenic upsurge which triggers off histamine release and this is essential for successful implantation. It has been known for a long time that there is a correlation between the histamine content of a tissue and the mast cell count (Riley & West, 1953). Mast cells have been demonstrated in the uterine tissue of golden hamsters (Harvey, 1964), guinea-pigs (Iversen, 1962), ferrets (Buchanan, 1966) and
N. Satayasthit, M. Tankeyoon and R. R. Chaudhury
W.H.O. Research Team, Chulalongkorn Hospital Medical School, Bangkok, Thailand
The contraceptive steroid, medroxyprogesterone acetate (MPA), which at a dose of 150 mg can be injected every 3 months, is being considered for more widespread use in family planning programmes of developing countries, e.g. Thailand. Since MPA, in contrast to the combined oestrogen-progestagen steroids, does not decrease but may actually increase milk secretion when administered to lactating women (Karim et al., 1971; Koetswang, Chiemprajert & Kochananda, 1972) it could be used more for contraception during lactation.
There is no information on the effects of MPA, when administered to the lactating rat, on the subsequent growth, sexual maturation and reproductive function of the young. MPA may be ingested through the milk, as has been demonstrated for the oestrogen-progestagen steroids (Laumas, Malkani & Laumas, 1971), and affect the release of the gonadotrophic hormones now known to be secreted very early after birth and
S. K. BATTA and R. R. CHAUDHURY
The intraluminal fluid from the rat uterus with an intrauterine silk thread suture exerts an anti-implantation effect when administered intraluminally into the uterus of a recipient rat on Day 2 and Day 4 but not on Day 6 of pregnancy. It is suggested that the intra-uterine device exerts its antifertility effect by release of a pharmacologically active agent.