No abstract

No abstract

Progesterone (P), required for successful pregnancy, influences autoimmune, infectious, and malignant diseases via adaptive and innate immune effects. P induces NK inhibitor progesterone induced blocking factor (PIBF) in CD8+ T cells. PIBF isoforms could permit solid tumor immune escape. Expression and modulation of PIBF and innate immune proteins by P in leukemia cells and leukocyte subpopulations have not been reported. Ten T, seven myeloid, six B, five epithelial, fibroblast BG9, G-CSF mobilized CD34+ stem cells, and peripheral blood mononuclear cells were screened for PIBF mRNA by RT-PCR, and protein by immunohistochemistry in SRIK-NKL, MOT, U937, HL60, R-CLL, MD-E, 729pH6neo, SRIH-B(ATL), SRIK-B(T-PLL), and MeWo. Cell lines expressing PIBF and exemplifying myeloid/monoblast, natural killer/T, and B lineages were cultured with and without 0.5 - 5 microM P or 0.5 - 0.05 microM mifepristone (RU486) for 24 h. Subsequently they were examined for changes in the expression of mRNA by RT-PCR and protein by immunohistochemistry for PIBF and some innate immune factors. All cells expressed PIBF mRNA; protein only in four (SRIK-NKL, U937, SRIK-B(T-PLL) and HL60) out of 10 cell lines tested. P increased and RU486 decreased PIBF in U937, SRIK-B(T-PLL) and SRIK-NKL. P upregulated TLR-4 in U937, and HNP1 - 3, LL-37, IRAK-2, and IRAK-4 in multiple lines and RU486 down regulated these. PIBF may be used by some leukemias to evade immune surveillance and is a potential therapeutic target. P may impact infection and autoimmunity via effects on LPS receptor, TLR signaling, and antimicrobial peptides.

A high DNA fragmentation index (DFI) when performing the sperm chromatin structural (SCSA) assay was claimed to be so specific for male subfertility that even IVF and ICSI did not result in live pregnancies. The present study was designed to corroborate or refute these findings. The SCSA test was performed on the male partner from couples failing to have a successful pregnancy despite at least 2 previous IVF attempts. In contrast to the aforementioned studies, ongoing pregnancies were found despite working with a group of recalcitrant patients. Nevertheless, a high DFI score was associated with a trend for lower ongoing pregnancy rates especially related to a high miscarriage rate. Other more recent studies seem to support our conclusions. A high DFI score should influence a patient to choose IVF as a therapeutic modality sooner, especially with ICSI.

Excessive generation of reactive oxygen species and increased peroxidation of the phospholipids in the membrane is proposed as a biochemical basis for the reduced activity of spermatozoa in cryopreserved semen. The possible role of alpha-tocopherol (VE) and ascorbic acid (VC) in improving the quality of frozen semen was investigated. Semen samples were divided into aliquots and frozen in freezing media with and without VC or VE. Sperm parameters, including motility after thawing and also at 2 h, % grade A motility (rapid and linear forward progression), and hypoosmotic swelling (HOS) scores, were measured in all samples. Vitamin C did not result in any improvement in sperm parameters studies. Vitamin E improved the post-thaw motility minimally. This improvement, although statistically significant, was actually very small. There were, however, wide variations between the samples. The motility improvement was considered in 5 of 12 samples, and HOS improved in some of the samples tested with VE. Future studies are needed to determine if these antioxidants can produce a consistent improvement in some individuals rather than help the majority of patients.

Insufficient progesterone, effect possibly more on immune factors rather than adequate endometrial development, can be an easy remedial cause of infertility by simply supplementing the luteal phase with either vaginal or intramuscular or oral (dydrogesterone) progesterone. Progesterone will also help to reduce miscarriage rates when follicle maturing drugs are used for those with regular menses but follicular maturation defects, or women with recurrent miscarriages. One mechanism of action seems to be related to production of an immunomodulatory protein, the progesterone-induced blocking factor either in the cytoplasm or in the circulation. PIBF inhibits cytotoxicity of natural killer cells. Cancer cells may 'borrow' the same mechanism to escape NK cell immunosurveillance. KEYWORDS: cancer • growth factors • immunosuppression • infertility • miscarriage • preterm delivery • progesterone• progesterone receptor • progesterone receptor antagonist • progesterone-induced blocking factor

Guanine nucleotide-binding regulatory proteins play key intermediary roles in regulating zona pellucida-mediated acrosomal exocytosis in mouse and bull sperm. Since human sperm possess a Gi-like protein and undergo the acrosome reaction in response to the human zona pellucida, we investigated whether this G protein plays a regulatory role in this exocytotic process. Zonae pellucidae isolated from eggs that had been inseminated but had shown no signs of fertilization after retrieval for in vitro fertilization and embryo transfer were pooled into groups of greater than or equal to 50 in order to reduce variability in biological responses due to the possible presence of ZP that had undergone modifications associated with the polyspermy block. Acid-solubilized zonae pellucidae were incubated with capacitated sperm, and the sperm then assessed for the acrosome reaction using both the P. sativum agglutinin and chlortetracycline fluorescence assays; both assays gave similar results. Sperm incubated with solubilized zonae pellucidae at a final concentration of 2, 4, or 6 ZP/microliter underwent acrosomal exocytosis to a similar extent as compared with A-23187. Sperm were incubated with 1 microgram/ml pertussis toxin during capacitation to functionally inactivate the Gi-like protein. Pertussis toxin treatment of sperm did not affect sperm motility and the ability of the cells to bind to structurally intact zonae pellucidae. Pertussis toxin, however, completely inhibited the percentage acrosome reactions induced by solubilized zonae pellucidae. By contrast, the A-23187-induced acrosome reaction was insensitive to PT treatment. Pertussis toxin inhibition of the zona pellucida-induced acrosome reaction occurred in a concentration-dependent manner with maximal effects observed at 100 ng/ml PT.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract