Effects of a copper-bearing intrauterine device on the ovarian function, body weight gain and pregnancy rate of nulliparous heifers.

A copper-bearing intrauterine device (IUD), designed to cause a slight distention of the uterus, was inserted through the cervix into each uterine horn of 230 heifers; an additional 230 heifers served as the control group. Blood was drawn at 0, 1, 2, 20 and 120 d for progesterone and testosterone assays. The heifers were checked twice daily for estrus and examined at 0, 60 and 120 d for weight gain. Thereafter they were bred over a 120-d period. The IUD caused anestrus in 98% of the heifers, with a daily weight gain 25.5 % higher than in the control heifers. Moreover, the device was 100% effective in preventing pregnancy. At 20 and 120 d after IUD insertion progesterone levels averaged 0.7 ng/ml, which was 4 to 5 times lower than in the control animals, suggesting a failure in ovulation or in corpus luteum (CL) formation due to the IUD. Simultaneously, testosterone values were increased up to 8 times in IUD-treated heifers, reaching a mean concentration of 163 pg/ml. Associated histological evaluations of the ovaries from UD-treated heifers revealed the presence of 2 or more cysts per ovary, with marked hyperthecosis in many antral follicles in which the granulosa cell layers were either thinned or lacking. The results suggest that the action of the copper-releasing IUD used in this study resulted in high contraceptive efficiency but also in disturbance of ovarian function. Our findings further raise the possibility of a cause and effect relationship between hyperandrogenism and the higher body weight gain observed in heifers treated with the IUD.

Interovarian communication for the control of follicular growth and corpus luteum function in the cebus monkey.

We have investigated the role of the utero-ovarian ligament (UOL) in the alternating ovulatory performance of the ovaries in the capuchin monkey. In intact animals, the ovulation rate was near 90%, with 67.5% of ovulations occurring in the left ovary. Sectioning the UOL in any phase of the cycle decreased the ovulation rate by 40%, and restricted ovulations to the ovary still connected to the uterus by the UOL. Estradiol and progesterone levels were significantly reduced throughout the following cycles in treated monkeys. Removal of the ovary that had been disconnected 18-20 months previous, restored both the ovulation rate and normal steroid levels. Histological study of the UOL revealed the presence of arteries, veins, lymph vessels, and nerves. Electrical stimulation of the UOL was followed by an abrupt discharge of estradiol by the ovary bearing the follicle, advancing ovulation which was followed by a normal luteal development. Conversely, stimulation of the ovary bearing a corpus luteum did not modify either the ovarian or the peripheral levels of ovarian steroids. The UOL ligament appeared to be functional for products arising from the uterus. The distribution and effects of hCG injected intrauterinely depended upon the day of the luteal phase. In the early luteal phase, hCG was distributed symmetrically between both ovaries, and increased the progesterone secretion by the ovulatory ovary only. In the late luteal phase, hCG was preferentially distributed to the ovulatory ovary, and increased the progesterone secretion by both ovaries. The present findings provide evidence for a local mechanism, throughout the UOL, controlling both the alternation of ovulation and the transfer of substances originating in the uterus that regulate the ovarian function in primates. © 1994 Wiley-Liss, Inc.

Interovarian relationship in the secretion of progesterone during the luteal phase of the capuchin monkey (Cebus apella).

In basal conditions, progesterone concentrations were similar in the ovarian veins of the ovary +CL (3211 +/- 526 ng/ml) and the ovary -CL (3165 +/- 554 ng/ml), but after blocking the blood flow between the ovary +CL and the uterus, the progesterone values in the vein draining the ovary -CL decreased to 1218 +/- 394 ng/ml (P less than 0.01). When [3H]progesterone was injected in the ovary +CL, the radioactivity appeared earlier and more concentrated in the vein draining the ovary -CL (30 sec, 0.53% of injected dose) than in the femoral vein (150 sec, 0.08% of injected dose). Removal of the ovary +CL was followed by a brief maintenance of peripheral progesterone within luteal-phase levels. The in-vitro progesterone production by a suspension of cells isolated from the corpus luteum was 47.5 +/- 12.8 ng/ml/2 h, whereas luteal-like cells isolated from the ovary -CL secreted 14.3 +/- 6.0 ng/ml/2 h (P less than 0.01) into the medium. We therefore suggest that the symmetrical and high secretion rate of progesterone by the ovaries of the capuchin monkey indicates a between-ovary communication system, and that the luteal-like tissue of the ovary -CL can produce relatively large amounts of progesterone.

Hormonal monitoring of early pregnancy by a direct radioimmunoassay of steroid glucuronides in first morning urine.

The usefulness of the direct 4-hour radioimmunoassay of estriol-16-glucuronide (E3G) and pregnanediol-3-glucuronide (P2G) in first morning urine (FMU) for establishing a prognosis of the early pregnancy outcome was evaluated in 106 patients that became pregnant. Microaliquots of FMU were serially assayed from day 3 of the conception cycle until day 80 of pregnancy. The E3G and P2G profiles of 19 pregnancies which terminated in spontaneous abortion with either a diagnosis of the blighted ovum syndrome (n = 11) or presumption of a corpus luteum/trophoblast failure (n = 8) have been compared with those of clinically normal pregnancies (n = 87). Normal pregnancies displayed typical patterns of E3G and P2G development, while variations were observed in abortive events that reflected changes of the fetoplacental unit.

Direct assay of urinary steroid glucuronides for monitoring the approach of ovulation.

The concentrations of estrone-3-glucuronide (E(1)3G) and pregnanediol-3-glucuronide (P(2)3G) in daily samples of early morning urine (EMU) were correlated with the levels of estradiol (E2), progesterone (P) and LH in respective plasma samples. Forty-six menstrual cycles were studied, in order to determine the practical usefulness of the urine assays for detecting: a) an individualized estrogen concentration threshold value, announcing the approach of ovulation. b) an individualized signal provided by P(2)3G in urine from which it can be assumed that ovulation has already occurred. The results showed that the concentration of E2 in plasma, in any day of the cycle, can be precisely inferred from the respective concentration of E(1)3G in EMU. The estimation of the plasmatic P values from those of P(2)3G in EMU had to be based on different factors according to the phase of the cycle, fact that suggests the presence of a phase-related variation in the glucuronization of P metabolites. Considering three consecutive E(1)3G urinary assay results, it was possible to identify a threshold value termed Estrogen-Peak Initiating Rise (E-PIR), which anticipated in 3.02 +/- 0.18 days the occurrence of an LH peak. The attempts to detect the occurrence of ovulation by an individualized urinary P(2)3G signal proved disappointing. The signal was detected, either before, simultaneously or after the LH peak.