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PubMed1989

Ventricular fibrillation detection by autocorrelation function peak analysis.

UNLABELLED: The use of reliable automatic ventricular fibrillation (VF) recognition techniques is critical in performing external automatic defibrillation. The authors' objective was to develop a method to detect VF and life-threatening arrhythmias, based on direct and simple peak analysis of the autocorrelation function (ACF). This method may differentiate between fibrillating and nonfibrillating rhythms, and in the first case between "course" and "fine" VF. ECG records during ventricular tachycardia (VT) and VF were obtained from patients during cardiac surgery. Segments 4 sec long were selected from tapes and digitized at 200 Hz, then split into three groups (VT, VF regular waveform, and VF irregular waveform). The positive peak P(j) of the ACF was defined as the maximum value between two function zeros, and RPL(j) represents the relation between P(j) and twice their own standard error. Parameter TR(1) was defined as the relation between P(1) width and the time of occurrence. ACFs were computed for the entire sample; RPL(j), D(j) = RPL(j) - RPL(j + 1), and TR(1) were calculated for every record. The results indicate that: (A) If RPL(1) greater than 1.2 and (1.6 greater than or equal to RPL(2) greater than 1) and (RPL(3) greater than 0.6 and D(1) greater than 0), then consider VT; (B) If (1.2 greater than or equal to RPL(1) greater than or equal to 1) and (1 greater than or equal to RPL(2) greater than or equal to 0.9) and D(1) greater than 9, then consider VT or VF with very regular waveform; (C) If (RPL(1) less than or equal to 1.8 and RPL(2) less than 0.9) or (RPL(2) less than 1.5 and D(1) less than 0) or RPL(3) less than 0.6, then consider VF. When 0.3 less than TR(1) less than 0.8, the underlying arrhythmia is VF or VT, and when it is outside this range, it is likely to be a supraventricular rhythm. CONCLUSIONS: (A) RPL(j) parameters have a high specificity for discriminating between VT and VF. The method is reliable and simple. (B) The TR(1) parameter together with RPL(j) allow discrimination between supraventricular tachycardias and ventricular originated tachyarrhythmias. (C) Further analysis must be done using problem-oriented arrhythmias data bases.

Data Interpretation, Statistical↗

PubMed1999

Role for retroperitoneal lymphadenectomy for testis cancer.

There continue to be several controversies surrounding the role for retroperitoneal lymphadenectomy (RPL) in the management of patients with germ cell cancer of the testis. The initial treatment options for those with clinical stage I disease are surveillance (orchiectomy only), RPL or chemotherapy. Survival rates are similar with RPL and surveillance. Surgical morbidity has been reduced as techniques for RPL continue to improve. The likelihood of early or late (> 2 years) recurrence in the retroperitoneum is almost eliminated by RPL. Fewer follow-up computerized tomography scans of the abdomen are required and there are opportunities to reduce the duration and methods of follow-up, compared with surveillance. For patients with stage II disease, chemotherapy and RPL are equally effective initial treatment options but many patients require a combined approach. Initial RPL should be reserved for patients with smaller volume disease and possibly with lower preoperative marker levels. With RPL, patients are accurately staged and cured most of the time without double treatment. Approximately 30% of those with larger masses will have residual disease after initial chemotherapy and will require RPL as a second treatment. The third indication for RPL is to excise residual retroperitoneal masses following primary chemotherapy. Models to predict the presence of residual viable tumor, rather than necrosis only, at the time of surgery have been developed. If the orchiectomy specimen contained no teratoma, the tumor markers normalize after three or four courses of chemotherapy, and if the residual mass on computerized tomography scan is less than 2 cm in diameter, the rate of viable tumor may be low enough to omit RPL. In this way, the greater morbidity often associated with post-chemotherapy RPL may be avoided.

Humans↗

PubMed2003

Polycystic ovary syndrome, the G1691A factor V Leiden mutation, and plasminogen activator inhibitor activity: associations with recurrent pregnancy loss.

Our specific aim was to assess associations of thrombophilia, hypofibrinolysis, and polycystic ovary syndrome (PCOS) with recurrent pregnancy loss (RPL) (>/=3 consecutive pregnancy losses < 20 weeks gestation). Prospective studies were performed in 33 Caucasian women referred for diagnosis and treatment of PCOS who were subsequently found to have RPL and in 16 Caucasian women referred for diagnosis and treatment of RPL, who did not have PCOS. Cases (PCOS-RPL, RPL without PCOS) were compared with controls (116 healthy Caucasian females) for the G1691A Factor V Leiden, G20210A prothrombin, C677T methylenetetrahydrofolate reductase (MTHFR), plasminogen activator inhibitor 4G/5G, and platelet glycoprotein PL A1A2 gene mutations. Cases were compared with controls (44 healthy adult Caucasian females) for serologic coagulation tests including homocysteine, proteins C, S, free S, antithrombin III, anticardiolipin antibodies IgG and IgM, dilute Russel's viper venom time, activated partial thromboplastin time, Factor VIII, Factor XI, lipoprotein (Lp)(a), and plasminogen activator inhibitor activity (PAI-Fx). The 33 Caucasian women with PCOS subsequently found to have RPL were 10% of a cohort of 322 Caucasian women who had >/= 1 previous pregnancy and had been referred for diagnosis and therapy of PCOS over a 4.3-year period. The Factor V Leiden G1691 mutation was present in 6 of 33 women (18%) with PCOS-RPL and in 3 of 16 women with RPL without PCOS (19%) versus 2 of 116 (1.7%) female controls, Fisher's P (p(f)) =.0016, p(f) =.013. The 33 PCOS-RPL cases also differed from the 44 female controls for high PAI-Fx (>21.1 U/mL), 38% versus 8%, p(f) =. 004. The thrombophilic G1691A Factor V Leiden mutation is associated with RPL in women with and without PCOS; hypofibrinolysis (high PAI-Fx) is also associated with RPL in women with PCOS.

Abortion, Spontaneous↗

PubMed1990

Molecular cloning and expression of rat placental lactogen-I complementary deoxyribonucleic acid.

A full-length cDNA clone for rat placental lactogen I (rPL-I) has been isolated from a phage lambda gt11 library containing cDNA synthesized from day 11 rat placental mRNA. By Northern blot analysis the rPL-I cDNA clone hybridizes to a 1.0-kilobase placental mRNA and appears as early as day 10 of gestation. Maximal expression of this mRNA was observed in day 11 and 12 placenta, and faint hybridization of the rPL-I cDNA was also detected in day 18 to term placenta. In contrast, the mouse clone hybridized to mRNA for mouse PL-I (mPL-I) only in day 10 mouse placenta (9). In vitro translation of rPL-I mRNA produced by transcription of the cDNA template yielded a 27-kDa polypeptide the size of the expected precursor protein which was immunoprecipitated by a monoclonal antibody to rPL-I. The rPL-I cDNA nucleotide sequence has been determined. The sequence is very similar to that for mPL-I and contains an open reading frame encoding a polypeptide of 230 amino acids compared to 224 for mPL-I. Comparison of the predicted primary translation product of rPL-I mRNA with that of mPL-I mRNA revealed that rPL-I shares 73% identity to mPL-I at the amino acid level. The predicted rPL-I protein shares 41% amino acid identity with rPL-II precursor, 24% with rat prolactin-like protein A, 26% with rat prolactin-like protein B, and 31% with rat PRL. In situ hybridization studies indicated that mRNA for rPL-I was present in a few rapidly dividing cells as early as day 8 of gestation, and by day 9 could be localized to giant cells which surround the conceptus.

Amino Acid Sequence↗

PubMed1999

Lack of association between serum antibodies to Chlamydia trachomatis and a history of recurrent pregnancy loss.

OBJECTIVE: To study the relation between recurrent pregnancy loss (RPL) and infection with Chlamydia trachomatis, and to compare the prevalence of antibodies to C. trachomatis in women with primary and secondary RPL. DESIGN: Prospective comparative study. SETTING: University hospital and university student health center. PATIENT(S): Seventy patients with RPL were selected from women attending an RPL outpatient clinic; 40 normal parous women and 94 asymptomatic sexually active women served as controls. INTERVENTION(S): Blood samples were collected during the clinical examinations for RPL. MAIN OUTCOME MEASURE(S): Serum immunoglobulin (Ig) G and IgA antibodies were detected by two independent methods, a recombinant ELISA specific to the genus Chlamydia and microimmunofluorescence testing specific to the species C. trachomatis. RESULT(S): There was no statistically significant difference in the frequencies of IgG or IgA between the women with RPL and the controls. The antibody frequencies were similar in the women with primary and secondary RPL. CONCLUSION(S): The presence of serum antibodies to C. trachomatis is not associated with RPL. Women with primary and secondary RPL do not differ with respect to the prevalence of antichlamydial antibodies. Thus, women with RPL do not benefit from screening for chlamydial IgG or IgA antibodies.

Abortion, Habitual↗

PubMed1996

Endocrine communication between conceptus and mother: placental lactogen stimulation of maternal behavior.

The possible role of the conceptus in stimulating the onset of maternal behavior through its secretion of placental lactogens and their passage into the brain was investigated in female rats. In the first study, significant mitogenic activity in the Nb2 lymphoma cell bioassay was detected in cerebrospinal fluid (CSF) samples collected by push-pull perfusion from rats on days 12-21 of pregnancy, coincident with the establishment of placental function. In contrast, mitogenic activity was absent from CSF in lactating and gonadectomized, virgin females. In a second study the mitogenic activity in day 12 pregnant samples was neutralized 71% with antibodies to rat placental lactogen-I (rPL-I) and > 90% with a combination of antibodies to rPL-I plus rPL-II. In contrast, activity on day 21 of pregnancy, 1 day prepartum, was reduced by antibodies to rPL-II (> 85%), but not by antibodies to rPL-I, indicating that the predominant lactogen in the CSF prepartum is rPL-II. The behavioral actions of placental secretions were assessed in the third experiment by infusing recombinant rPL-I and purified rPL-II directly into the medial preoptic area of the brain of steroid-primed, nulliparous rats. Latencies to respond maternally to foster young were significantly reduced in rPL-I- and rPL-II-treated rats (2- to 3-day latencies) when compared with latencies in control females (5- to 6-day latencies). Thus, the conceptus through its secretion of rPLs which apparently gain access to the CSF helps to prime the pregnant female's brain to respond maternally at the end of gestation. This endocrine communication between the developing conceptus and pregnant female appears to be an important part of the biological system which helps to establish successful maternal care.

Animals↗

PubMed1984

Ovarian and fetal control of rat placental lactogen and prolactin secretion at midpregnancy.

The role of the fetus and ovarian steroids in stimulating rat placental lactogen (rPL) secretion and in regulating nocturnal PRL surges was investigated. On day 10, pregnant rats were ovariectomized (O) and/or fetectomized (F). Those rats injected with steroids received 0.1 microgram estradiol benzoate (E) or 4 mg progesterone (P) in oil sc, or both (PE). Blood samples were taken by cardiac puncture at 0500 h, on days 10 through 14. OPE rats showed slightly depressed serum rPL levels on days 11 and 12 and normal growth of the conceptuses. Ovariectomized rats given P alone also showed significant growth of the conceptus, although less than the OPE rats, demonstrating the necessity for estrogen during pregnancy. PRL surges were no longer present in these groups on day 11, similar to controls. Ovariectomized rats had very low rPL levels, and the nocturnal PRL surges continued for 2 extra days. Fetectomized and OF animals also had very low rPL levels and one extra PRL surge. P counteracted the detrimental effects of fetectomy on rPL secretion; yet placental uterine growth was not greater than in F animals. Thus, increased placental mass was not always correlated with increased rPL secretion. The results show that P is necessary to maintain rPL secretion in the pregnant rat, although estradiol and P in combination is most effective. The fetus also is essential to stimulate both placental growth and rPL secretion. The inverse correlation between rPL and PRL levels on days 11 and 12 suggests that rPL normally terminates the PRL surges at midpregnancy.

Animals↗

PubMed2005

Autosomal genes of autosomal/X-linked duplicated gene pairs and germ-line proliferation in Caenorhabditis elegans.

We report molecular genetic studies of three genes involved in early germ-line proliferation in Caenorhabditis elegans that lend unexpected insight into a germ-line/soma functional separation of autosomal/X-linked duplicated gene pairs. In a genetic screen for germ-line proliferation-defective mutants, we identified mutations in rpl-11.1 (L11 protein of the large ribosomal subunit), pab-1 [a poly(A)-binding protein], and glp-3/eft-3 (an elongation factor 1-alpha homolog). All three are members of autosome/X gene pairs. Consistent with a germ-line-restricted function of rpl-11.1 and pab-1, mutations in these genes extend life span and cause gigantism. We further examined the RNAi phenotypes of the three sets of rpl genes (rpl-11, rpl-24, and rpl-25) and found that for the two rpl genes with autosomal/X-linked pairs (rpl-11 and rpl-25), zygotic germ-line function is carried by the autosomal copy. Available RNAi results for highly conserved autosomal/X-linked gene pairs suggest that other duplicated genes may follow a similar trend. The three rpl and the pab-1/2 duplications predate the divergence between C. elegans and C. briggsae, while the eft-3/4 duplication appears to have occurred in the lineage to C. elegans after it diverged from C. briggsae. The duplicated C. briggsae orthologs of the three C. elegans autosomal/X-linked gene pairs also display functional differences between paralogs. We present hypotheses for evolutionary mechanisms that may underlie germ-line/soma subfunctionalization of duplicated genes, taking into account the role of X chromosome silencing in the germ line and analogous mammalian phenomena.

Animals↗

PubMed1999

Influence of rat placental lactogen-I on the development of whole rat embryos in culture.

Rat placental lactogen-I (rPL-I), the first prolactin-like hormone expressed in the placenta during pregnancy in the rat, is known to influence maternal functions. In the present study, we have investigated the effects of rPL-I on the growth and development of cultured whole rat embryos. Rat embryos, with or without ectoplacental cone (EPC) attached, were explanted at day 9 of gestation. After 48 h of culture, the embryos, enclosed by the yolk sacs, were assessed by the presence of visible heart contractions ('heart beats'), crown-rump length (CRL) and yolk sac diameter (YSD). When intact embryos with EPC were cultured, the concentrations of rPL-I and rPL-II (products of EPC) in the medium were 850+/-841 and 92+/-181 ng/ml respectively (means+/-s.e.m.). In embryo cultures with the EPC removed, rPL-I levels decreased to</=10 ng/ml, and only 70% of the embryos were viable, with visible heart beats. In the viable embryos, both CRL and embryonic DNA synthesis were reduced compared with controls, and the addition of rPL-I (1 microg/ml) did not prevent this reduction. YSD and yolk sac DNA synthesis were also reduced compared with control embryos, and the addition of rPL-I significantly prevented this decrease by 45%. In embryos cultured without EPC in the presence of neutralizing rabbit anti-rat prolactin serum (anti-rPRL), embryonic and yolk sac DNA synthesis were reduced by 35% compared with embryos exposed to normal rabbit serum. Addition of rPL-I significantly increased (P<0.05) embryonic and yolk sac growth. Thus the effects of rPL-I on embryo growth could only be seen in the absence of prolactin. The addition of human prolactin in the presence of anti-rPRL also resulted in significant increases (P<0.05) in embryonic DNA synthesis and CRL. These results suggest that rPL-I may substitute for prolactin to influence the growth of the rat embryo.

Animals↗

PubMed1996

Interaction of recombinant rat placental lactogen-I with extracellular domains of prolactin receptors from three species.

Rat placental lactogen-I (rPL-I), expressed in rat uteri at midpregnancy, belongs to the GH/PRL/cytokine family of hormones (Wallis, 1992), all members of which exhibit a similar mechanism of receptor activation. Lactogenic activity of rPL-I as determined by Nb2 lymphoma cell bioassay was slightly higher than that of hGH. rPL-I was capable also of stimulating beta-casein production in mouse HC-11 cells. Competitive binding experiments using [125I]hGH or [125I]bPL and purified prolactin receptor extracellular domains (PRLR-ECDs) from rat (r), rabbit (rb), and bovine (b) showed rPL-I to be 12, 40, and 7-fold, respectively, less effective than hGH when competing with [125I]hGH. Displacement of [125I]bPL by rPL-I from rPRLR-ECD and rbPRLR-ECD was also 4-, and 30-fold less effective, respectively, than that by bPL. rPL-I did not compete at all with [125I]bPL for binding to bPRLR-ECD. In contrast, competitive binding experiments with [125I]hGH to a microsomal fraction of Nb2 cells showed rPL-I to be slightly more active than hGH. The stoichiometries of the complexes formed by rPL-I with rbPRLR-ECD, rPRLR-ECD, and bPRLR-ECD were studied by gel filtration. Whereas a 1:1 complex was formed between rPL-I and rPRLR-ECD and rbPRLR-ECD, no complex could be detected between rPL-I and bPRLR-ECD. The present results support the hypothesis that transient forms of a homodimer complex may be sufficient to initiate the biological signal, despite its short half-life.

Animals↗

PubMed2004

Do the right precordial leads during exercise testing contribute to detection of coronary artery disease?

BACKGROUND: It is still unknown whether or not the additional right precordial leads (RPL) during exercise testing contribute to detection of coronary artery disease (CAD). HYPOTHESIS: The aim of this study was to evaluate the RPL during exercise testing for the detection of CAD. METHODS: The study included 157 consecutive patients (116 men and 41 women, mean age 66 years) suspected of having CAD, who underwent conclusive treadmill exercise testing (heart rate reached at least 85% of the predicted maximum or positive electrocardiogram [ECG] changes were exhibited) and coronary angiography. During exercise testing, the ECG was recorded with the standard 12 leads and 4 RPL (V3R, V4R, V5R, V6R). RESULTS: Of the 157 patients, 67 had CAD (> 75% stenosis in at least one major coronary artery), and 64 had positive ST changes in the standard ECG leads during exercise testing. Using the conventional 12-lead method, sensitivity and specificity were 76 and 86%, respectively. Only three patients exhibited positive changes in the RPL leads; all had > 0.1 mV ST elevation in one of the RPL leads with > 0.1 mV ST elevation in aVR. Two of these patients had significant right coronary artery lesions and the other had a lesion of the left anterior descending artery which perfused the inferior as well as the anteroseptal area. In the standard 12 leads, one of the patients with an abnormal RPL and a right coronary lesion was negative, while the other two patients were positive. Combining RPL with the conventional 12-lead method, sensitivity and specificity were 78 and 86%, respectively. Therefore, RPL did not improve the accuracy of the exercise ECG. CONCLUSION: The use of RPL during exercise testing may contribute to the detection of ischemia perfused by the right coronary artery; however, it does not improve the diagnostic accuracy of the exercise test.

Aged↗

PubMed2003

High basal estradiol level and FSH/LH ratio in unexplained recurrent pregnancy loss.

BACKGROUND: The potential role of diminished ovarian reserve in unexplained recurrent pregnancy loss (RPL) in a retrospective comparative analysis. METHODS: Eighty women with RPL underwent routine work-up to exclude known associations of RPL. Serum FSH, LH and E(2) levels were assessed on the 3rd day of the menstrual cycle. Following investigation, 58 women failed to reveal an identifiable cause and are therefore classified as unexplained RPL. Control group consisted of women in whom the cause of abortions was known such as uterine septum and parental chromosomal abnormalities. Mean age, gravidity, parity, presence of infertility, previous number of miscarriages, duration of marriage were similar in both groups. Day 3 serum levels of FSH, E(2) and FSH: LH ratios were compared in the two groups. RESULTS: Elevated FSH concentrations were equally distributed in the unexplained RPL and control groups. Both day 3 E(2) and FSH:LH ratio were elevated in the unexplained RPL group compared with the control group ( p=0.0066 and p=0.0187 respectively). The percentage of women with elevated FSH and/or E(2) levels on day 3 were significantly higher in the unexplained RPL group than in controls ( p=0.0045). CONCLUSIONS: Unexplained RPL may be associated with diminished ovarian reserve and should be considered in the workup of RPL.

Abortion, Habitual↗

PubMed2005

Evidence-based care of recurrent miscarriage.

Between 0.5 and 1.0% of couples experience recurrent pregnancy loss (RPL), which is defined as three or more consecutive miscarriages. Losses are classified as pre-embryonic (<5 weeks), embryonic (5-10 weeks) or fetal (>10 weeks). Genetic abnormalities are responsible for RPL in 2-4% of these couples. Inadequate progesterone production has been proposed a cause of RPL and progesterone is given to prevent miscarriage, despite a lack of supportive evidence. The factor V Leiden and prothrombin G20210A mutations are common inherited thrombophilias also associated with RPL. Antenatal thromboprophylaxis is sometimes recommended although no data exist regarding efficacy. Antiphospholipid syndrome is known to cause RPL and antenatal thromboprophylaxis reduces the risk of miscarriage. Uterine abnormalities might also result in RPL. About 50% of cases of RPL have no identifiable cause. Alloimmune incompatibility has been proposed as a cause for RPL in these women. The concept of alloimmune-related RPL has not been scientifically validated.

Abortion, Habitual↗

PubMed2002

Aberrant cytokine production by peripheral blood mononuclear cells in recurrent pregnancy loss?

BACKGROUND: Successful pregnancy may depend on a Th2-type cytokine response, whilst, conversely, a poor pregnancy outcome may be associated with an increase in Th1 cytokines and a concomitant decrease in Th2 cytokines. This prospective study was designed to elucidate whether a failure of the cytokine shift pre-dated miscarriage and was therefore likely to be an aetiological factor in recurrent pregnancy loss (RPL). METHODS: Cytokine production by stimulated peripheral blood mononuclear cells from 46 pregnant women who had previously suffered idiopathic RPL during early pregnancy was compared with 25 gestationally age-matched pregnant controls and 11 non-pregnant women. RESULTS: Production of IFN-gamma was lower in pregnant than in non-pregnant women and even lower in RPL pregnant women (P = 0.0191). IL-10 was increased in pregnant women compared with non-pregnant controls, and further increased in RPL patients (P = 0.026). IL-4 was also increased in women with RPL (P = 0.0001). No differences in IFN-gamma, IL-10 or IL-4 secretion were observed in RPL patients who subsequently miscarried compared with those who successfully completed the pregnancy. RPL women with a successful reproductive outcome had similar concentrations of TNF-alpha to pregnant women, RPL women who subsequently miscarried had significantly lower levels than either pregnant women (P = 0.02) or non-pregnant controls (P = 0.0004). CONCLUSIONS: Contrary to our hypothesis, the cytokine shift, which appears to characterize normal pregnancy, was accentuated rather than diminished in RPL pregnant women.

Abortion, Habitual↗

PubMed2005

Maternal CD46H2 and IL1B-5111 homozygosity in T helper 1-type immunity to trophoblast antigens in recurrent pregnancy loss.

BACKGROUND: Women with recurrent pregnancy loss (RPL) and T-helper (Th)1-type immunity to trophoblast antigens have an increased frequency of the IL1B-511*1 promoter variant. Since CD46 gene products also regulate maternal immune responses including Th1 immunity, we investigated whether CD46 gene polymorphisms are also associated with RPL in women with and without Th1 immunity to trophoblast, and the possibility of a synergistic effect with the IL1B-511*1 promoter variant. METHODS: A case-controlled study was performed to document HindIII site polymorphism in intron 1 of the CD46 gene in 131 women with RPL and 72 fertile controls. Clinical information, Th1-type immune responsiveness to trophoblast in women with RPL history, and IL1B promoter allelotypes for this cohort were documented in a previous study. RESULTS: The frequency of the CD46H*2 allele and CD46H*2 homozygosity were significantly increased in women with RPL compared with fertile controls (P<0.028 and P<0.011). CD46H*2 homozygosity was highly associated with RPL-Th1(+) (32.4 versus 9.7% in fertile controls, P<0.0045). Logistic regression analysis revealed that women homozygous for both the IL1B-511*1 and CD46H*2 alleles had an extremely high risk of RPL-Th1(+) [exponential coefficients (EC)=24]. Among women with RPL, homozygosity at both alleles, but not each alone, significantly increased the risk of Th1 immunity to trophoblast antigens (EC=16), suggesting a possible genetic interaction between these two alleles in the development of Th1 immunity. CONCLUSIONS: The combination of homozygosity for both IL1B-511*1 and CD46H*2 alleles is a high risk factor for RPL-Th1(+).

Abortion, Habitual↗

PubMed2003

Expression of membrane-bound HLA-G at the maternal-fetal interface is not associated with pregnancy maintenance among patients with idiopathic recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) has many known aetiologies. However, using current diagnostic testing, a large fraction of recurrent pregnancy losses remain unexplained. Many of these may have immune underpinnings. HLA-G is a non-classical MHC class I product whose fairly restricted expression at the maternal-fetal interface suggests a role in successful embryonic implantation and/or subsequent pregnancy maintenance. The study of immune-mediated RPL should be enhanced by comparing groups of idiopathic RPL patients with normal fetal chromosomes to RPL patients with known chromosomal abnormalities in their index pregnancies. We hypothesized that if alteration of HLA-G expression at the maternal-fetal interface were associated with immune-mediated RPL, such changes might be detectable using these comparisons. HLA-G protein expression at the maternal-fetal interface in maternal and gestational age-matched women with history of idiopathic RPL and normal male fetuses were compared with expression in RPL patients with known fetal trisomy 16 in their index pregnancy. We detected no significant quantitative differences in the levels of HLA-G between these groups of RPL patients. Within the limitations of this study, we conclude that HLA-G expression is not a major immunological determinant of pregnancy maintenance among patients with idiopathic RPL.

Abortion, Habitual↗

PubMed1983

Secretion of rat placental lactogen by the fetal placenta and its inhibitory effect on prolactin surges.

The various products of conception were examined for their ability to secrete rat placental lactogen (rPL), cause normal termination of the diurnal and nocturnal prolactin (Prl) surges and maintain progesterone secretion. Serum rPL, highest on Day 12, was measured by Nb2 lymphoma cell bioassay. Surgery was performed on Day 8, leaving only the uterus in aborted animals, the decidua in the decidua intact animals, or the placenta and decidua in the fetectomized animals. In control rats, rPL levels were elevated by the afternoon of Day 8, the last day the diurnal Prl surge is seen. By Day 10, the last day of the nocturnal surge, rPL levels were extremely high. Fetectomized animals exhibited both the diurnal and nocturnal surges for 2 additional days while rPL secretion was only slightly above baseline levels. Both the decidua-intact and aborted animals continued both daily Prl surges with barely detectable rPL levels. Progesterone secretion was maintained through Day 14 only in the control animals. It is concluded the rPL is secreted by the fetal trophoblastic cells, not the decidua, and that the presence of the fetus is necessary for secretion of normal amounts of rPL and maintenance of pregnancy. Further support is given to the hypothesis that it is rPL which terminates the Prl surges at midpregnancy.

Animals↗

PubMed1984

Ovarian factors inhibit and fetal factors stimulate the secretion of rat placental lactogen.

Removal of fetuses at day 14 of gestation (Ftx14) in the pregnant rat leads to a marked suppression of serum levels of rat placental lactogen (rPL-II). One might attribute this to compromised placental growth in the absence of a fetus. However, if ovariectomy and fetectomy (Ftx14 Ovx14) are carried out at the same time, a great increase in serum rPL-II levels is seen. This occurs despite a significant decrease in placental weight. When Ftx14 was performed on day 14 and Ovx was delayed 1, 2, or 3 days, the expected large increase in serum rPL-II was progressively attenuated compared to that seen when Ftx and Ovx were carried out simultaneously. Daily administration of 17 beta-estradiol (4 micrograms/rat X day) to Ftx14 Ovx14 pregnant rats resulted in a significant suppression of rPL-II and elevation of rPRL levels, a reversal of what is seen for these hormones in untreated Ftx14 Ovx14 animals. To test whether 17 beta-estradiol was acting through rat PRL (rPRL), serum levels of rPRL were elevated in Ftx13 Ovx13 animals with pimozide (0.6 mg/kg), a dopamine receptor blocker. There was no effect of this treatment on rPL-II levels. In late pregnancy (day 17) serum rPL-II levels remained high after removal of half the fetuses (1/2 Ftx), compared to the rapid fall in pregnant rats in which all fetuses were removed (Ftx17). Serum levels were also elevated in 1/2 Ftx animals compared to those in which half of the fetuses and placentas were removed by hemi-hysterectomy, suggesting that the increase in rPL-II levels in 1/2 Ftx animals was due to a stimulatory effect of the remaining fetuses on all of the placentas. These results indicate that the presence of the fetus is necessary for the normally observed increase in rPL-II levels in late pregnancy. In conclusion, fetal stimulators and ovarian inhibitors influence rPL-II secretion.

Animals↗