Vitamin D (Vit D) is important for the regulation of reproductive physiology. In humans, maternal Vit D deficiency has been implicated in several reproductive- and pregnancy-related disorders. Very few data are available regarding the Vit D status in male partners of couples attempting pregnancy. This observational study (IRB Prot. N. 078/13) aimed to evaluate whether low Vit D serum levels in males might decrease the rate of successful conception in couples attempting pregnancy. Male and female partners of infertile couples (n = 102) were classified into 2 GROUPS according to normal (≥30 ng/ml) or low (below 30 ng/ml) serum Vit D levels in male partners. Semen analysis was performed in each male participant based on the WHO reference criteria. The female partners of both groups were subjected to 3 consecutive cycles of gonadotropin-induced mono-ovulation. The main outcome measures included the clinical pregnancy rate, delivery per patient and per cycle, and miscarriage rate between the 2 groups evaluated at the end of the three-month period of the study. In male partners of both groups, standard semen analysis did not highlight substantial differences in sperm concentration, sperm progressive motility, or typical form. The pregnancy rates per patient and per cycle and delivery rates per patient and per cycle were all significantly higher (p< 0.05) in couples with normal Vit D levels. These results suggest the existence of a relationship between male Vit D serum levels and semen ability to begin a pregnancy during cycles of timed vaginal intercourse.

The human species is biologically distinguished by low fertility. In fact, with each menstrual cycle, a couple at the peak of their reproductive capacity has only about a 30% chance of conceiving. The WHO states infertility as “a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected intercourse.”Assisted reproductive technology (ART) consists of all treatments or procedures that include the in vitro handling of both human oocytes and sperm or of embryos, for the purpose of establishing a pregnancy.The techniques are usually divided into three broad categories: First level techniques: Intrauterine and Intracervical Insemination (IUI/ICI), the simpler and less invasive ones, such as intrauterine insemination (IUI) with or without Intracervical Insemination (ICI) ovarian stimulation. Second level techniques: the more complex and more invasive ones that can be performed under local anesthesia or deep sedation, which differ from the basic techniques as they involve manipulation of female and male gametes and because they require in vitro fertilization. Among these techniques the IVF (In Vitro Fertilization and Embryo Transfer), ICSI (Intracytoplasmic Sperm Injection), and the possible cryopreservation of male and female gametes and embryos. Third level techniques procedures that require general anesthesia with intubation, including: laparoscopic egg retrieval, intra-tubal transfer of male and female gametes (GIFT), zygotes (ZIFT) and /or embryos (TET) laparoscopically; microsurgical sampling of gametes from the testicle: Testicular Sperm Extraction (TESE), Microsurgical Testicular Sperm Extraction (microTESE), Testicular Sperm Aspiration (TESA); microsurgical sampling of gametes from the epididymides: Percutaneous Epididymal Sperm Aspiration (PESA) and Microsurgical Epididymal Sperm Aspiration (MESA). In all assisted reproduction techniques, the seminal fluid receives a treatment able to induce capacitation “in vitro” so that the activated spermatozoa, at the threshold of the acrosomal reaction, can interact with the mature oocytes. Preimplantation Genetic Screening (PGS) and Preimplantation Genetic Diagnosis (PGD) are highly specialized procedures which involve removing three to four cells from a 5–6 day old blastocyst and testing them for chromosomal abnormalities prior to transferring the embryo into a woman’s uterus. According to data reported from the European IVF-Monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE), the clinical pregnancy rates (PR) per aspiration and per transfer are 28.0% and 34.8%, respectively. After ICSI, the corresponding rates are 24% and 33.5%. ART can alleviate the burden of infertility on individuals and families, but it can also present challenges to public health as evidenced by the high rates of multiple delivery, preterm delivery, and low birth-weight delivery experienced with ART.

Cystic fibrosis (CF) airways are affected by a deranged repair of the damaged epithelium resulting in altered regeneration and differentiation. Previously, we showed that human amniotic mesenchymal stem cells (hAMSCs) corrected base defects of CF airway epithelial cells via connexin (CX)43-intercellular gap junction formation. In this scenario, it is unknown whether hAMSCs, or fibroblasts sharing some common characteristics with MSCs, can operate a faster repair of a damaged airway epithelium. A tip-based scratch assay was employed to study wound repair in monolayers of CFBE14o- cells (CFBE, homozygous for the F508del mutation). hAMSCs were either co-cultured with CFBE cells before the wound or added to the wounded monolayers. NIH-3T3 fibroblasts (CX43+) were added to wounded cells. HeLa cells (CX43-) were used as controls. γ-irradiation was optimized to block CFBE cell proliferation. A specific siRNA was employed to downregulate CX43 expression in CFBE cells. CFBE cells showed a delayed repair as compared with wt-CFTR cells (16HBE41o-). hAMSCs enhanced the wound repair rate of wounded CFBE cell monolayers, especially when added post wounding. hAMSCs and NIH-3T3 fibroblasts, but not HeLa cells, increased wound closure of irradiated CFBE monolayers. CX43 downregulation accelerated CFBE wound repair rate without affecting cell proliferation. We conclude that hAMSCs and fibroblasts enhance the repair of a wounded CF airway epithelium, likely through a CX43-mediated mechanism mainly involving cell migration.

The pathomechanisms of preeclampsia (PE), a complication of late pregnancy characterized by hypertension and proteinuria, and due to improper placentation, are not well known. Mesenchymal stem cells derived from the amniotic membrane (AMSCs) may play a role in PE pathogenesis as placental homeostasis regulators. PLACenta-specific protein 1 (PLAC1) is a transmembrane antigen involved in trophoblast proliferation that is found to be associated with cancer progression. We studied PLAC1 in human AMSCs obtained from control subjects (n = 4) and PE patients (n = 7), measuring the levels of mRNA expression (RT-PCR) and secreted protein (ELISA on conditioned medium). Lower levels of PLAC1 mRNA expression were observed in PE AMSCs as compared with Caco2 cells (positive controls), but not in non-PE AMSCs. PLAC1 antigen was detectable in conditioned medium obtained from PE AMSCs, whereas it was undetectable in that obtained from non-PE AMSCs. Our data suggest that abnormal shedding of PLAC1 from AMSC plasma membranes, likely by metalloproteinases, may contribute to trophoblast proliferation, supporting its role in the oncogenic theory of PE.