lactoferrin and Infertility--Female

The secretory glycoprotein lactoferrin (LF) is suggested to ameliorate overweight regardless of non-genetic or genetic mechanisms. Although maternal overweight represents a key predictor of offspring growth, the efficacy of LF on fertility problems in overweight and obese mothers remains unknown. To address this issue, we examined the effect of LF ingestion by analyzing overweight mice (Institute of Cancer Research (ICR) mice with high-fat diets; HF mice) and obese mice (

Topics: Animals; Diabetes Mellitus, Type 2; Female; Fertility; Fertility Agents, Female; Infertility, Female; Lactoferrin; Mice; Obesity; Overweight; Up-Regulation

We prospectively investigated if oral enteric coating lactoferrin supplementation improves the reproductive outcomes in infertile women with a history of repeated implantation failure (RIF) and non-Lactobacillus-dominant (Lactobacillus rate < 90%) microbiota (NLDM) in vaginal secretions (VS)/endometrial fluid (EF).. Paired VS/EF samples were obtained from RIF women and control infertile women (non-RIF group) for microbiome analysis. Chronic endometritis (CE) was diagnosed histopathologically and hysteroscopically. In a pilot study, oral enteric coating lactoferrin (700 mg/day, at least 28 consecutive days) was administered to eligible patients with NLDM in VS/EF. Their reproductive outcomes in the subsequent vitrified-warmed embryo transfer cycles were followed up.. While CE was more prevalent (OR 2.41, 95% CI 1.02-5.63, p = 0.042) in the RIF group (29.1%, n = 117) than in the non-RIF group (14.5%, n = 55), The NLDM rate was similar between the two groups (44.4 vs 52.7%). Lactoferrin supplementation improved NLDM in 43.2% of RIF women (n = 37). Within the RIF group, the live birth rate in the subsequent cycles was higher (OR 10.67, 95% CI 1.03 - 110.0, p = 0.046) in women with improved microbiota (57.1%, n = 14) than in those with unimproved microbiota (11.1%, n = 9).. Unlike CE, NLDM was not unique to RIF but was common in infertile women. Although the therapeutic effect of the oral lactoferrin supplementation on NLDM was limited in a pilot study, the reproductive outcomes were better in RIF women who overcame NLDM than in those who failed. Randomized controlled trials are required to confirm the results. TRIAL REGISTRATION NUMBER AND DATE FOR PROSPECTIVELY REGISTERED TRIALS: UMIN-CTR 000036990, June 7, 2019.

Topics: Dietary Supplements; Dysbiosis; Embryo Implantation; Endometritis; Endometrium; Female; Humans; Infertility, Female; Lactoferrin; Live Birth; Pilot Projects; Pregnancy

Phospholipase C beta 1 (PLCβ1) is a downstream effector of G-protein-coupled receptor signalling and holds central roles in reproductive physiology. Mice with a disruption in the Plcβ1 gene are infertile with pleiotropic reproductive defects, the major reproductive block in females being implantation failure. Here, PLCβ1 was demonstrated at the luminal and glandular epithelia throughout the pre- and peri-implantation period, with transient stromal expression during 0.5-1.5 days post coitum (dpc). Examination of implantation sites at 4.5 dpc showed that in females lacking functional PLCβ1 (knock-out (KO) females), embryos failed to establish proper contact with the uterine epithelium. Proliferating luminal epithelial cells were evident in KO implantation sites, indicating failure to establish a receptive uterus. Real-time PCR demonstrated that KO implantation sites had aberrant ovarian steroid signalling, with high levels of estrogen receptor α, lactoferrin and amphiregulin mRNA, while immunohistochemistry revealed very low levels of estrogen receptor α protein, possibly due to rapid receptor turnover. KO implantation sites expressed markedly less fatty acid amide hydrolase and monoacylglycerol lipase, indicating that endocannabinoid metabolism was also affected. Collectively, our results show that PLCβ1 is essential for uterine preparation for implantation, and that defective PLCβ1-mediated signalling during implantation is associated with aberrant ovarian steroid signalling and endocannabinoid metabolism.

Topics: Amidohydrolases; Amphiregulin; Animals; EGF Family of Proteins; Embryo Implantation; Embryo, Mammalian; Endocannabinoids; Epithelial Cells; Estradiol Congeners; Estrogen Receptor alpha; Female; Gene Expression Regulation, Developmental; Glycoproteins; Infertility, Female; Intercellular Signaling Peptides and Proteins; Lactoferrin; Mice; Mice, Knockout; Monoacylglycerol Lipases; Ovary; Phospholipase C beta; Signal Transduction; Uterus

To investigate the level of lactoferrin (LF) in follicular fluid (FF), as well as the correlation between the LF concentration of FF, fertilization rate, and embryo quality.. Retrospective study.. In vitro fertilization program at the Showa University School of Medicine, Tokyo, Japan.. Follicular fluid was obtained from 35 IVF patients, aged 25-34 years.. In total, 70 FF and serum samples were collected at the time of oocyte harvesting (44 of the oocytes were fertilized, and 26 were not). The LF concentration in FF was assayed via ELISA.. The mean LF concentration in FF of the fertilized group (500.2 +/- 35.5 ng/mL) was significantly higher than that in the unfertilized group (379.7 +/- 45.1 ng/mL). A positive correlation between follicular size and LF concentration was not found (r = 0.214). However, a high LF concentration in FF was indicative of good embryo quality.. High LF concentrations in FF correlate with both a high fertilization rate and good embryo quality.

Topics: Adult; Biomarkers; Cells, Cultured; Embryo, Mammalian; Female; Fertilization in Vitro; Follicular Fluid; Humans; Infertility, Female; Lactoferrin; Oocytes; Pregnancy

Topics: Biochemical Phenomena; Biochemistry; Blood Proteins; Body Temperature; Cervix Mucus; Contraceptives, Oral; Female; Gonadal Steroid Hormones; Humans; Infertility, Female; Lactoferrin; Muramidase; Ovulation