Male Placentas Research Articles

Does fetal gender affect cytotrophoblast cell activity in the human term placenta? Correlation with maternal hCG levels

Background. Pregnant women with female fetuses have higher maternal serum human chorionic gonadotropin (hCG) levels than pregnant women with male fetuses. Ki-67, a cell proliferation and activity marker, is confined mostly in the nuclei of villous cytotrophoblasts of the human placenta. In this study, we examined the effect of fetal gender on the cytotrophoblast cell activity in human term placenta, with special regard to maternal serum and cord blood hCG levels. Methods. Thirty-four uncomplicated, singleton, term pregnancies (17 male and 17 female fetuses) were recruited in the study. hCG was measured in maternal peripheral serum and umbilical cord blood. Placental samples were collected in each patient during the cesarean section. Cytotrophoblast cell activity was measured by using immunohistochemistry for Ki-67 antigen. Ki-67 staining index values of the cytotrophoblasts were compared between the female and male placentas. Results. Maternal serum and cord blood hCG levels were higher in pregnant women with female fetuses than in those carrying male fetuses. There was no sex difference in Ki-67 immunostaining rates of the cytotrophoblast cells. There was no correlation between maternal serum and cord blood hCG levels and Ki-67 staining index values of the cytotrophoblast cells. Conclusions. The difference in maternal serum and cord blood hCG levels in correlation with the fetal gender is not associated with cytotrophoblast cell activity in the human term placenta. The gender of the fetus does not seem to affect the regulation of cytotrophoblast cell proliferation.

Genetic and developmental analysis of X-inactivation in interspecific hybrid mice suggests a role for the Y chromosome in placental dysplasia.

It has been shown previously that abnormal placental growth, i.e., hyper- and hypoplasia, occurs in crosses and backcrosses between different mouse (Mus) species. A locus that contributes to this abnormal development has been mapped to the X chromosome. Unexpectedly, an influence of fetal sex on placental development has been observed, in that placentas attached to male fetuses tended to exhibit a more pronounced phenotype than placentas attached to females. Here, we have analyzed this sex dependence in more detail. Our results show that differences between male and female placental weights are characteristic of interspecific matings and are not observed in intraspecific Mus musculus matings. The effect is retained in congenic lines that contain differing lengths of M. spretus-derived X chromosome. Expression of the X-linked gene Pgk1 from the maternal allele only and lack of overall activity of two paternally inherited X-linked transgenes indicate that reactivation or lack of inactivation of the paternal X chromosome in trophoblasts of interspecific hybrids is not a frequent occurrence. Thus, the difference between male and female placentas seems not to be caused by faulty preferential X-inactivation. Therefore, these data suggest that the sex difference of placental weights in interspecific hybrids is caused by interactions with the Y chromosome.

ELEVATED PLACENTAL ESTRADIOL: A POSSIBLE ETIOLOGICAL FACTOR OF HUMAN CRYPTORCHIDISM

It has been convincingly argued that the increasing incidence of reproductive abnormalities in human males may be associated with increased estrogen exposure during gestation. We documented the expression of estradiol in the syncytiotrophoblast and placenta of males born with cryptorchidism and normal genitalia, respectively. Tissue from newborn placentas was fixed in glutaraldehyde and embedded in ePON for immunohistological procedures. Cryptorchidism was unilateral in 6 males and bilateral in 1. Semithin histological sections of placental biopsies of these 7 males and 7 randomly selected, normal male placentas were analyzed immunohistochemically with a polyclonal anti-estradiol-17 beta, 6-keto antibody. The weak expression of estradiol in the placentas of normal males was localized predominantly at the basal part of the syncytiotrophoblast in the terminal placental villi. In contrast, all placentas of cryptorchid males had strong expression of estradiol at the basal portion of the syncytiotrophoblast. The increased expression of estradiol in the syncytiotrophoblast may have an impact on testicular descent.

Cytolytic T Lymphocytes Recognize an Antigen Encoded by MAGE-A10 on a Human Melanoma

Abstract From melanoma patient LB1751, cytolytic T lymphocytes (CTL) were generated that lysed specifically autologous tumor cells. To establish whether these CTL recognized one of the Ags that had previously been defined, a CTL clone was stimulated with cells expressing various MAGE genes. It produced TNF upon stimulation with target cells expressing MAGE-A10. The Ag was found to be nonapeptide GLYDGMEHL (codons 254–262), which is presented by HLA-A2.1. This is the first report on the generation of anti-MAGE CTL by autologous mixed lymphocyte-tumor cell culture (MLTC) from a melanoma patient other than patient MZ2, from whom the first MAGE gene was identified. MAGE genes are expressed in many tumors but not by normal tissues except male germline cells and placenta, which do not express HLA molecules. Therefore, the identification of an antigenic peptide derived from MAGE-A10 adds to the repertoire of tumor-specific shared Ags available for anti-tumoral vaccination trials.

Assignment of the human ubiquitous receptor gene ( UNR) to 19q13.3 using fluorescence in situ hybridization

Human UNR cDNAs were used to screen a Lambda FIX II human male placenta genomic library. Phage DNA from clones hybridizing to UNR cDNA was characterized by Southern hybridization and restriction mapping, and two different clones (hG10 and hG12) with inserts of 15-20 kb were chosen for fluorescence in situ hybridization (FISH) analysis. Biotin-labeled probes were prepared from phage DNA by nick-translation using Bio-11-dUTP. FISH was performed as described previously. Hybridization was detected with fluorescien-conjugated avidin, and chromosomes were identified by staining with 4,6-diamidino-2-phenylindole-dihydrochloride (DAPI).

Developmental Toxicity of 2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) in the Most TCDD-Resistant and -Susceptible Rat Strains

To gain insight into the relationship between TCDD acute toxicity and teratogenicity, developmental effects of TCDD were assessed in the most TCDD-resistant and -sensitive rat strains, Han/Wistar (Kuopio [H/W]; LD 50 > 7200 μg/kg) and Long-Evans (Turku AB [L-E]; LD 50 about 10 μg/kg), respectively. A single oral dose of 0, 1, or 10 μg/kg TCDD was given to mated female H/W rats on Gestation Day 8 or 12. In L-E rats, the doses were 0, 1, or 5 μg/kg TCDD and the exposure took place on Gestation Day 8. Fetuses were examined on Gestational Day 20 for external and soft tissue malformations. TCDD inhibited maternal body weight gain (corrected for weight of uterus with fetuses) at the 10 μg/kg dose in H/W rats and at 1 and 5 μg/kg in L-E rats. Absolute and relative thymus weights decreased dose-dependently in dams of both strains, but relative liver weights increased only in high-dose H/W dams and low-dose L-E dams. There was a striking interstrain difference in teratogenic outcomes. Over 70% of the live L-E fetuses at 5 μg/kg of TCDD exhibited cleft palate, while this effect did not occur in any H/W fetus. Conversely, hydronephrosis and gastrointestinal hemorrhaging appeared dose dependently in live H/W fetuses only. In L-E dams, the incidence of resorptions and late fetal deaths increased up to 75% at 5 μg/kg. Edematous dead fetuses and a slightly increased number of resorptions (together 35%) were found in H/W dams at 10 μg/kg. Fetal body weights and placental weights decreased at 5 μg/kg in L-E rats. In H/W rats, the weights of male placentas decreased at both doses of TCDD. Thus, sensitivity of adult rats to the acute lethal effect of TCDD does not correlate with susceptibility to its developmental toxicity.

3D display of stillbirth in Indonesian obstetrics. Part 7: Expansion to neonatal death.

The associations between hospital neonatal death and stillbirth birthweight and infant sex and maternal age and selected complications were analyzed for 36802 singleton-birth deliveries occurring in Indonesia in 1978-80 and displayed in 3-dimensional form. In all 3 low-birthweight categories there was an excess risk of neonatal death (31%) for boys as compared to girls. Low-birthweight males also demonstrated an excess (15%) neonatal death share of perinatal death. In terms of maternal factors the neonatal death risk was 13.0/1000 for no complications of pregnancy compared with 41.8/1000 in cases of prolonged or obstructed labor and 111.9/1000 for placenta previa with little relative variation across maternal ages. It is hypothesized that there is a link between neonatal death low-birthweight male infants and placenta previa. The precise nature of this link could constitute a focus for surveillance research with maternity care monitoring data from developing countries.

Transcriptional control of HLA-A,B,C antigen in human placental cytotrophoblast isolated using trophoblast- and HLA-specific monoclonal antibodies and the fluorescence-activated cell sorter.

Human placental cell suspensions prepared by trypsin digestion were analyzed with several monoclonal antibodies on a multiparameter fluorescence-activated cell sorter (FACS). Five distinct cell populations were isolated on the basis of size and quantitative differences in the coordinate expression of cell surface antigens detected by monoclonal antibodies against an HLA-A,B,C monomorphic determinant (MB40.5) and against human trophoblasts (anti-Trop-2). By FACS analysis and after sorting we clearly identified the major cell population as cytotrophoblasts based on several independent criteria, including presence of trophoblast-specific surface antigens, Trop-1, and Trop-2; absence of all HLA class I, class II, and beta 2-microglobulin (beta 2m) antigens; absence of the pan-leucocyte and monocyte antigens, HLe1 and LeuM1, respectively; presence of Y-chromatin in a male placenta; presence of placental and not liver alkaline phosphatase; and a large, mononuclear morphology. These procedures provide a reproducible method for obtaining highly purified human cytotrophoblast populations for further studies. We measured by molecular hybridization (RNA or Northern blots) the HLA-A,B,C and beta 2m mRNA in total RNA extracted from sorted cytotrophoblasts. We find that normal human cytotrophoblasts have extremely small amounts of HLA-A,B,C mRNA: approximately 300 times less than that in the lymphoid cell line LCL-721 or normal lymphocytes. In contrast, they have approximately 11% the level of beta 2m mRNA present in LCL-721 cells. Thus, HLA-A,B,C antigen expression on human cytotrophoblasts is limited by the level of HLA heavy chain mRNA.

Repeated nucleotide sequences in human main band DNA

Male and female human placenta DNA was fractionated in an Ag +-Cs 2SO 4 density gradient. The different fractions along the gradient were analyzed by Hae III endonuclease digestion. Within the main band DNA on the light side a component having a Hae III digestion pattern similar to that of human satellite III DNA has been identified. This component which might be defined as a cryptic satellite accounts for at least 3% of the total human DNA and has a different position than human satellite III in Ag +-Cs 2SO 4.

The effect of fetal hypophysectomy on placental biosynthesis of progesterone in rhesus.

Placental slices from intact rhesus fetuses were incubated without added substrate. The incubated tissue levels of progesterone (P4) differed according to the sex of the fetus. Slices from female placentas contained significantly more P4 than did those of males. The addition of pregnenolone (P5) to the incubation media caused tissue levels of P4 to increase 1.5 to 3 times control tissue levels for both female and male placentas. Moreover, the sex difference in P4 biosynthesis was eliminated by adding P5 to the incubations. Since control incubations of male placental tissue produced less P4 than those of females, the net increase in P4 synthesis with added P5 was greater for male than female placental tissue. These observations indicated that the step(s) in P4 biosynthesis which were affected by the fetal genotype lay between cholestrol and P5. Incubation of placental slices derived from decapitated fetuses secreted significantly less P4 into the incubation medium than those of intact fetuses. Moreover, the sex difference in the media content of P4 was eliminated. However, decapitation did not eliminate the sex difference in the tissue content of P4 during control incubations. When P5 was added to the incubations, media and tissue levels of P4 increased significantly over control levels for placentas from both sexes. However, the addition of P5 to the incubations from decapitated males did not restore P4 production in the tissue or the medium to levels observed for intact males. However, this did occur when P5 was added to incubations from decapitated females. It appears that fetal decapitation decreased cholesterol side chain cleaving activity and delta5-3beta-hydroxy-steroid dehydrogenase content of the placenta. These data indicate that hormones of fetal origin may control P4 production by the placenta.

Scanning electron microscopy of human reproductive physiology.

Recent findings on the scanning electron microscopical (SEM) structures of epithelium of female and male reproductive organs spermatozoa placenta amniotic cells umbilical cord neonatal blood cells and pathologies of their structures - carcinoma of the endometrium cervix vagina and vulva - are reviewed. The methodology in preparation of soft tissue cervical mucus and amniotic tissues is described including pinning fixation dehydration and drying mounting and metal coating and viewing with the SEM. There are striking morphological differences between the tissue organization of the mucosa of different segments of the reproductive tract. These morphological di fferences are discussed in terms of observed physiological functions. SEM is a useful tool in studying infertility the status of the newborn monitoring fetal maturity and carcinoma diagnosis.

The effect of fetal sex on placental biosynthesis of progesterone.

The concentration of endogenous progesterone (P4) in the rhesus placenta ranged from 1.9 to 9.9 ng/100 mg tissue (Mean ± SE = 4.9 ± .82). There was no correlation between the sex of the fetus and the endogenous P4 in placental tissue. However, when placental slices were incubated without added substrate, female placentas produced significantly more P4 than male placentas. The addition of cholesterol to the incubations did not increase P4 production over control levels. Progesterone biosynthesis from both male and female placentas increased significantly over control levels when pregnenolone (P5) was added to the media. The total production of P4 with P5 tended to be greater for male placentas than for female placentas, but the difference was not significant. However, the net increase over control levels in P4 production with P5 was greater for male placentas than for female placentas. These observations indicate that the step(s) in progesterone biosynthesis that are affected by the fetal genotype lie betw...

Presence of Androgens in the Placenta

Although the presence of androgenic substances in the placenta is mentioned by several authors, these fail to make any specific citation to the original work, and an examination of the more common indices is no more encouraging.Siebka1 examined 2 placentae following operative abortion and failed to find any androgens in the 4-5-month-old organs. If there is any positive evidence of the occurrence of androgens in the placenta, it has not found its way into the current literature.The purpose of this study was to determine whether or not the presence of androgens in the placenta could be demonstrated.Three male and 3 female full term placentae were secured, washed as free of blood as possible and extracted according to the Gallagher and Koch method. The extracts were assayed both on capons and by the colorimetric methods.The colorimetric assay∗ indicated the presence of one international unit in 60.7 g of male placenta, and one I.U. in 69.4 g of female placenta. The capon test showed for the male placentae o...