State-of-the-art in reproductive bench science: Hurdles and new technological solutions.

Infertility is a growing issue in modern society, being the fifth highest serious global disability according to the World Health Organization. To study infertility and other reproductive system complications, bench science still relies on 2D and animal studies, which regularly have been criticized due to their inability to mimic the human body. Particular challenges in 2D studies include the inability to mimic fluid dynamics, gametes modulation and their crosstalk, hormonal patterns as well as the low quality and viability of gametes and embryos. Animal models also present other drawbacks, namely the absence of menstruation, making it difficult to establish a reliable predictive model for the human system. Additionally, reproductive studies should not be limited to the fallopian tube as the sole responsible for most infertility cases, but instead the research spectrum should be widened to the whole reproductive system given the tight interconnectivity between each and every organ. In the last few decades, new in vitro technologies have been developed and applied to the study of reproductive system complications. These systems allow to create complex three-dimensional structures, which are therefore able to more closely resemble specific microenvironments and provide more realistic physical and biochemical cues. 3D (bio)printing, organoids and organs-on-chips are some of the dynamic technologies which are replacing conventionally employed static 2D culture. Herein, we provide an overview of the challenges found in conventional 2D and animal models of the reproductive system and present potential technological solutions for those same challenges.

Angiotensin-converting enzyme inhibitors after renal transplantation.

The blockade of the renin-angiotensin-aldosterone system may limit the progression of graft dysfunction in patients receiving kidney transplantations. We retrospectively evaluated the safety and efficacy of angiotensin-converting enzyme inhibitors (ACEI) in renal allograft recipients. Fifty-seven cadaveric kidney recipients (58% of recipients), were prescribed an ACEI (lisinopril). The indications for ACEI were isolated proteinuria (1 patient), erythrocytosis (6 patients), and arterial hypertension (50 patients). The choice of an ACEI for blood pressure control was due to presence of left ventricular hypertrophy (2 patients), mild proteinuria (4 patients), and high hemoglobin (4 patients). There was a significant reduction in the mean arterial pressure after 1 month (P = .0004) and 1 year (P = .0002) of therapy. Overall, the estimated glomerular filtrate rate (eGFR), calculated using the Cockcroft-Gault equation, remained unchanged. Among patients who had serum creatinine values above 2.0 mg/dL at the beginning of ACEI therapy, there was a significant rise in eGFR from 39.3 +/- 13.2 to 44.1 +/- 16.8 mL/min after 6 months (P = .01), and 43.3 +/- 17.3 mL/min after 1 year (P = .04). In patients with erythrocytosis, the hemoglobin showed a significant and sustained reduction after 1 month (P = .004) and 1 year (P = .001). Six patients suspended ACEI owing to adverse events: cough (n = 4), worsening of graft function (n = 1), and hypotension (n = 1). Six patients required erythropoiesis-stimulating agents. No patient suspended treatment owing to hyperkalemia. In conclusion, ACEI were well tolerated, safe, and effective antihypertensive agents in kidney graft recipients. They seemed to have some beneficial effect in preserving GFR in patients with worse graft function.