Cytokines in culture media of preimplantation embryos during in vitro fertilization: Impact on embryo quality.

Cytokine support of embryonic development includes promotion of implantation and protection of blastomeres from cell stress and apoptosis. Correlations between embryo quality and concentrations of specific cytokines in culture media of human embryos have been investigated for many years. The aim of this study was to assess the concentrations of cytokines in preimplantation embryo culture media and to investigate their relationships with embryo quality and in vitro fertilization (IVF) outcomes. Seventy-two samples were obtained from 39 infertile couples undergoing IVF or intracytoplasmic sperm injection treatment between October 2018 and May 2019. Each embryo was cultured separately, and the embryo culture medium was collected 72 h after fertilization. Before embryo transfer on day 3, a morphological evaluation of each embryo was performed. Cytokine concentrations of each culture medium were analyzed for 23 selected cytokines using the Multiplex Cytokine/Chemokine Panel II Assay (Merck Millipore®). The results were categorized into two groups (top-quality and non-top-quality embryos). The median age of the 39 patients was 34 years. Nine of 23 cytokines were quantified and compared between the top-quality embryo group and non-top-quality embryo group. Among the nine cytokines, CCL15, CCL27, and CXCL-12 were significantly elevated in the top-quality embryo group. These results suggested that specific cytokines measured in human embryo culture media can be used to predict embryo quality and IVF outcomes.

Hormone autocrination by vascularized hydrogel delivery of ovary spheroids to rescue ovarian dysfunctions.

The regeneration potential of implantable organ model hydrogels is applied to treat a loss of ovarian endocrine function in women experiencing menopause and/or cancer therapy. A rat ovariectomy model is used to harvest autologous ovary cells while subsequently producing a layer-by-layer form of follicle spheroids. Implantation of a microchannel network hydrogel with cell spheroids [vascularized hydrogel with ovarian spheroids (VHOS)] into an ischemic hindlimb of ovariectomized rats significantly aids the recovery of endocrine function with hormone release, leading to full endometrium regeneration. The VHOS implantation effectively suppresses the side effects observed with synthetic hormone treatment (i.e., tissue overgrowth, hyperplasia, cancer progression, deep vein thrombosis) to the normal levels, while effectively preventing the representative aftereffects of menopause (i.e., gaining fatty weight, inducing osteoporosis). These results highlight the unprecedented therapeutic potential of an implantable VHOS against menopause and suggest that it may be used as an alternative approach to standard hormone therapy.