Long-Term Effects of ART on the Health of the Offspring.

Assisted reproductive technologies (ART) significantly increase the chance of successful pregnancy and live birth in infertile couples. The different procedures for ART, including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), intrauterine insemination (IUI), and gamete intrafallopian tube transfer (GIFT), are widely used to overcome infertility-related problems. In spite of its inarguable usefulness, concerns about the health consequences of ART-conceived babies have been raised. There are reports about the association of ART with birth defects and health complications, e.g., malignancies, high blood pressure, generalized vascular functional disorders, asthma and metabolic disorders in later life. It has been suggested that hormonal treatment of the mother, and the artificial environment during the manipulation of gametes and embryos may cause genomic and epigenetic alterations and subsequent complications in the health status of ART-conceived babies. In the current study, we aimed to review the possible long-term consequences of different ART procedures on the subsequent health status of ART-conceived offspring, considering the confounding factors that might account for/contribute to the long-term consequences.

Composition and effects of seminal plasma in the female reproductive tracts on implantation of human embryos.

The function of seminal plasma involves acting as a transport medium for sperm and as a means of communication between the reproductive tissues of the male and female. It is also a vital factor to prime the reproductive tracts of the female for optimal pregnancy. When the reproductive tract of the female is exposed to seminal plasma, serious alterations take place, enhancing pathogen and debris clearance observed in the uterus throughout mating. It is also capable of supporting embryo growth, promoting the receptivity of the uterus, and establishing tolerance to the semi-allogenic embryo. Moreover, seminal plasma is capable of regulating the functions of several female reproductive organs and providing an ideal condition for effective embryo implantation and pregnancy. It is believed that the health state of the offspring is affected by exposure to seminal plasma. For the treatment of infertility, assisted reproductive technologies have been extensively employed. The application of seminal plasma as a therapeutic approach to enhance the development of embryo competency and rate of implantation, receptivity of endometrium, and establishment of maternal immune tolerance in cycles of ART appears possible. Herein, current knowledge on the composition of seminal plasma and the physiological roles it possesses on various parts of the female reproductive tract are summarized. Moreover, the role of seminal plasma in the development of embryos, implantation, and the following fetal growth and survival have been reviewed in this article.

Altered Immune Response and Implantation Failure in Progesterone-Induced Blocking Factor-Deficient Mice.

Earlier data suggest that progesterone-induced blocking factor (PIBF) is involved in implantation. The present study therefore aims to investigate the consequences of functional PIBF deficiency during the peri-implantation period. CD1 female mice were injected intraperitoneally with 2 µg anti-PIBF monoclonal antibody on days 1.5 and 4.5 of pregnancy. The number of implantation sites and resorption rates were recorded on day 10.5. PIBF+ decidual NK cells and B cells were detected by immunohistochemistry or immunofluorescence. Decidual and peripheral NK activity was assessed by flow cytometry. A prime PCR array was used for determining the differential expression of genes involved in lymphocyte activation and Th1 or Th2 differentiation in CD4+ and CD8+ spleen cells from pregnant anti-PIBF-treated and control mice. Anti-PIBF treatment in the peri-implantation period resulted in impaired implantation and increased resorption rates in later pregnancy. The number of PIBF+ decidual NK cells decreased, while both decidual and peripheral NK activity increased in the anti-PIBF-treated mice. B cells were absent from the resorbed deciduas of anti-PIBF-treated mice. The genes implicated in T cell activation were significantly downregulated in CD4+ and increased in CD8+ of the anti-PIBF-treated animals. The gene for IL-4 was significantly downregulated in CD4+ cells while that of IL-12A was upregulated in CD8+ cells of anti-PIBF-treated animals. These data suggest that the lack of PIBF results in an impaired T cell activation, together with Th1 differentiation and increased NK activity, resulting in implantation failure.

The decidua-the maternal bed embracing the embryo-maintains the pregnancy.

The decidua has been known as maternal uterine tissue, which plays essential roles in protecting the embryo from being attacked by maternal immune cells and provides nutritional support for the developing embryo prior to placenta formation. However, there are questions that still remain to be answered: (1) How does the decidua supply nutrition and provide a physical scaffold for the growing embryo, before placental vascular connection is established? (2) How is the balance between preventing an anti-embryo immune response and protecting both embryo and mother from infections established? To understand basic personas in decidual tissues, we review the structure of the decidua composed of terminally differentiated uterine stromal cells, blood vessels, and a number of repertoire of uterine local immune cells, including the well-known uterine natural killer (uNK) cells and recently discovered innate lymphoid cells (ILCs). Decidual macrophages and uterine dendritic cells (DCs) are supposed to modulate adaptive immunity via balancing cytokines and promoting generation of regulatory T (Treg) cells. During decidualization, vascular and tissue remodeling in the uterus provide nutritional and physical support for the developing embryo. Secretion of various cytokines and chemokines from both the embryo and the decidual cells activates multiple signaling network between the mother and the embryo upon implantation. Defects in the decidual development during early pregnancy result in loss of pregnancy or complications in later gestational stage.