Current treatments of subfertile couples are usually empiric, as the true cause of subfertility often remains unknown. Therefore, we outline the role of nutritional and biochemical factors in reproduction and subfertility. A literature search was performed using MEDLINE, Science Direct and bibliographies of published work with both positive and negative results. The studies showed that folate has a role in spermatogenesis. In female reproduction, folate is also important for oocyte quality and maturation, implantation, placentation, fetal growth and organ development. Zinc has also been implicated in testicular development, sperm maturation and testosterone synthesis. In females, zinc plays a role in sexual development, ovulation and the menstrual cycle. Both folate and zinc have antioxidant properties that counteract reactive oxygen species (ROS). Thiols, such as glutathione, balance the levels of ROS produced by spermatozoa and influence DNA compaction and the stability and motility of spermatozoa. Oocyte maturation, ovulation, luteolysis and follicle atresia are also affected by ROS. After fertilization, glutathione is important for sperm nucleus decondensation and pronucleus formation. Folate, zinc, ROS and thiols affect apoptosis, which is important for sperm release, regulation of follicle atresia, degeneration of the corpus luteum and endometrial shedding. Therefore, the concentrations of these nutrients may have substantial effects on reproduction. In conclusion, nutritional and biochemical factors affect biological processes in male and female reproduction. Further research should identify pathways that may lead to improvements in care and treatment of subfertility.

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The balance and distribution of epithelial cell types is required to maintain tissue homeostasis. A hallmark of airway diseases is epithelial remodeling, leading to increased goblet cell numbers and an overproduction of mucus. In the conducting airway, basal cells act as progenitors for both secretory and ciliated cells. To identify mechanisms regulating basal cell fate, we developed a screenable 3D culture system of airway epithelial morphogenesis. We performed a high-throughput screen using a collection of secreted proteins and identified inflammatory cytokines that specifically biased basal cell differentiation toward a goblet cell fate, culminating in enhanced mucus production. We also demonstrate a specific requirement for Notch2 in cytokine-induced goblet cell metaplasia in vitro and in vivo. We conclude that inhibition of Notch2 prevents goblet cell metaplasia induced by a broad range of stimuli and propose Notch2 neutralization as a therapeutic strategy for preventing goblet cell metaplasia in airway diseases.

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In this study, the semen analysis results of a fertile population were compared with those from a subfertile population, in order to establish normal cut-off values for the standard semen parameters with the aid of receiver operating characteristic (ROC) curve analysis. The fertile group comprised healthy males (n = 107) without any history of fertility problems, the partners of whom had had a spontaneous pregnancy within one year of unprotected intercourse and were pregnant at the time of the male's inclusion into the study. A total of 103 males from couples attending the infertility clinic, and with an initial sperm count of <20x10(6)/ml were recruited to form the subfertile population. The best discriminating parameter between the two populations was sperm morphology evaluated according to WHO criteria at a cut-off point of 31% normal spermatozoa. The other cut-off values were at 8% for the acrosome index, 45% for motility, and 4% normal spermatozoa for strict criteria. Recalculating the ROC curve cut-off values based on an assumed 50% prevalence of subfertility in an assisted reproductive setting, the cut-off points were reduced to 21% and 3% normal spermatozoa for WHO and strict criteria respectively. For motility, the new cut-off value was at 20% motile spermatozoa, for motility quality at 3.5 (on a scale of 1-6), the acrosome index at 3% normal acrosomes, and the teratozoospermia index at 2.09.

Elevated total plasma homocysteine (tHcy) concentrations are considered a risk factor for neural tube defects (NTD) and cardiovascular disease. Supplementation with folic acid decreases the risk of women having children with NTD. In both sexes, it decreases tHcy levels. We investigated the efficacy of natural dietary folate in improving folate and homocysteine status. We performed a 4-wk dietary controlled, parallel design intervention trial with 66 healthy subjects (18-45 y) divided into 3 treatment groups: the dietary folate group, the folic acid group and the placebo group. Each day each group was fed a different diet. The dietary folate group received a diet high in vegetables and citrus fruit (total folate content approximately 560 microgram) plus a placebo tablet. The folic acid group received a diet naturally low in folate (approximately 210 microgram) plus 500 microgram folic acid and placebo tablet on alternate days, i.e., 250 microgram folic acid/d. And the placebo group received the same low-folate diet as the folic acid group plus a placebo tablet. After 4 wk of intervention, folate status improved, and tHcy concentrations decreased in both the dietary folate and the folic acid groups. From the amount of additional folate (350 microgram/d) and folic acid (250 microgram/d) consumed, the relative bioavailability of dietary folate compared to folic acid was calculated to be 60-98%, depending on the endpoint used. In conclusion, increasing the consumption of vegetables and citrus fruit, both good sources of folate, will improve folate status and decrease tHcy concentrations. This may contribute to the prevention of cardiovascular disease and NTD in the general population

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Background: An elevated plasma total homocysteine concentration is a risk factor for cardiovascular disease and neural tube defects. A high daily intake of supplemental folic acid is known to decrease total homocysteine concentrations. Objective: We studied the effect of low-dose folic acid administration (250 or 500 g/d) for 4 wk on plasma total homocysteine concentrations and folate status. We also investigated whether total homocysteine concentrations and blood folate concentrations returned to baseline after an 8-wk washout period. Design: In this placebo-controlled study, 144 healthy women aged 18-40 y received 500 g folic acid/d, 500 g folic acid every second day (250 g/d), or a placebo tablet with their habitual diet (mean dietary folate intake: 280 g/d). Results: Administration of 250 and 500 g folic acid/d for 4 wk significantly increased folate concentrations in plasma (P < 0.001) and red blood cells (P < 0.01). Total homocysteine concentrations decreased significantly (P < 0.001) in women (n = 50) who took 250 g folic acid/d [mean (± SEM) deviation from baseline: Ϫ11.4 ± 1.98%] and in women (n = 45) who took 500 g folic acid/d (Ϫ21.8 ± 1.49%). Eight weeks after the end of the intervention period (week 12), plasma total homocysteine concentrations in the folic acid-supplemented groups had not returned to baseline (week 0). Conclusions: Doses of folic acid as low as 250 g/d, on average, in addition to usual dietary intakes of folate significantly decreased plasma total homocysteine concentrations in healthy, young women. An 8-wk washout period was not sufficient for blood folate and plasma total homocysteine concentrations to return to baseline concentrations.Am J Clin Nutr 1999;69:99-104.