Xue Ma

Dear Editor,Testosterone is a fundamental sex hormone made by testicular Leydig cells and affects numerous sexual and nonsexual functions. Testosterone deficiency (TD) is characterized by low testo...

Reproductive tract infection is an important factor leading to male and female infertility. Among female infertility factors, microbial and viral infections are the main factors affecting female reproductive health and causing tubal infertility, ectopic tubal pregnancy and premature delivery. Among male infertility factors, 13–15% of male infertility is related to infection. Defensins are cationic antibacterial and antiviral peptides, classified into α-defensins, β-defensins and θ-defensins. Humans only have α-defensins and β-defensins. Apart from their direct antimicrobial functions, defensins have an immunomodulatory function and are involved in many physiological processes. Studies have shown that defensins are widely distributed in the female reproductive tract (FRT) and male reproductive tract (MRT), playing a dual role of host defence and fertility protection. However, to our knowledge, the distribution, regulation and function of defensins in the reproductive tract and their relation to reproduction have not been reviewed. This review summarizes the expression, distribution and regulation of defensins in the reproductive tracts to reveal the updated research on the dual role of defensins in host defence and the protection of fertility. A systematic search was conducted in PubMed using the related keywords through April 2022. Related data from original researches and reviews were integrated to comprehensively review the current findings and understanding of defensins in the human reproductive system. Meanwhile, female and male transcriptome data in the GEO database were screened to analyze defensins in the human reproductive tracts. Two transcriptome databases from the GEO database (GSE7307 and GSE150852) combined with existing researches reveal the expression levels and role of the defensins in the reproductive tracts. In the FRT, a high expression level of α-defensin is found, and the expression levels of defensins in the vulva and vagina are higher than those in other organs. The expression of defensins in the endometrium varies with menstrual cycle stages and with microbial invasion. Defensins also participate in the local immune response to regulate the risk of spontaneous preterm birth. In the MRT, a high expression level of β-defensins is also found. It is mainly highly expressed in the epididymal caput and corpus, indicating that defensins play an important role in sperm maturation. The expression of defensins in the MRT varies with androgen levels, age and the status of microbial invasion. They protect the male reproductive system from bacterial infections by neutralizing lipopolysaccharide and downregulating pro-inflammatory cytokines. In addition, animal and clinical studies have shown that defensins play an important role in sperm maturation, motility and fertilization. As a broad-spectrum antimicrobial peptide without drug resistance, defensin has great potential for developing new natural antimicrobial treatments for reproductive tract infections. However, increasing evidence has shown that defensins can not only inhibit microbial invasion but can also promote the invasion and adhesion of some microorganisms in certain biological environments, such as human immunodeficiency virus. Therefore, the safety of defensins as reproductive tract anti-infective drugs needs more in-depth research. In addition, the modulatory role of defensins in fertility requires more in-depth research since the current conclusions are based on small-size samples. At present, scientists have made many attempts at the clinical transformation of defensins. However, defensins have problems such as poor stability, low bioavailability and difficulties in their synthesis. Therefore, the production of safe, effective and low-cost drugs remains a challenge. The dual roles of defensins in the human reproductive system: host defence and protection of fertility.

Context: It is still unknown whether the dietary inflammatory index (DII) is associated with sex hormones and sex hormone binding globulin (SHBG) in adult women.Objective: This study examined the association between DII and sex hormones and SHBG in U.S. adult women.Design and Participants: This was a cross-sectional study. A total of 2,092 female participants (age ≥ 20) from the 2013–2016 National Health and Nutrition Examination Survey were enrolled. Dietary inflammatory potential was assessed by DII based on 24-h dietary recall. SHBG was assessed using immuno-antibodies and chemo-luminescence, whereas sex hormones were measured by ID-LC–MS/MS.Results: The average DII was 0.21 ± 1.68, ranging from −4.54 (most anti-inflammatory) to 4.28 (most pro-inflammatory). After adjusting all covariates, a per-unit DII increase in DII tertile 3 was related to an 8.05 nmol/L SHBG decrease compared to DII tertile 1 (P = 0.0366). Subgroup analysis stratified by perimenopausal period found that this negative association remained strong but only existed in women before (β = −3.71, 95% CI: −7.43, −0.12, P = 0.0423) the perimenopausal period. Interaction terms were added to both subgroup analyses and found no significant heterogeneity among different body mass index (BMI) or perimenopausal groups (P > 0.05). Treshold analyses showed that the association of age with SHBG was an inverted U-shaped curve (inflection point: age = 50 yrs).Conclusion: A proinflammatory diet caused decreased SHBG. However, more well-designed studies are still needed to validate and verify the causal relationship between DII and sex hormones and SHBG.

Purpose This study aimed to investigate the association between the dietary inflammatory index and lifetime kidney stone prevalence. Methods We performed a cross-sectional study utilizing the 2013–2014 National Health and Nutrition Examination Survey data. Data were available on 2192 participants aged > 20 years with a complete kidney stone history and 24 h dietary intake interview. Weighted multivariable linear regression, subgroup analyses, and interaction terms were employed. Covariates including age, race, sex, energy and protein intake, total serum calcium, serum iron, PIR, phosphorus, serum/urine creatinine, HDL, glucose, diastolic and systolic pressure, education level, eGFR, BMI, albuminuria, diabetes, smoking status, and marital status were hierarchically adjusted in three different models. Results The average dietary inflammatory index for 2192 participants was − 0.11 ± 1.73, ranging from − 4.52 to 4.28. In the fully adjusted model, participants in the highest dietary inflammatory index tertile (the most proinflammatory) had 72% higher odds of the lifetime prevalence of kidney stones than those in tertile 1 (OR = 1.72, 95% CI: 1.03, 2.88, P = 0.0367). Subgroup analysis showed that the association between the dietary inflammatory index and kidney stone history was only statistically significant in the younger age (age ≥ 60), female, Mexican American groups, married people or people without diabetes, hypertension, low eGFR, and albuminuria. Conclusions There is a positive association between the dietary inflammatory index and self-reported kidney stones in US adults, which indicates that dietary patterns could greatly impact kidney stone prevalence.

Thyroid function has a close link with inflammation. However, it is still unknown whether the dietary inflammatory potential is associated with thyroid function. We aimed to assess the relationship among them using the data from the National Health and Nutrition Examination Survey (NHANES). This study was a cross-sectional study, where weighted multivariable linear regression, subgroup analyses, and interaction terms were employed. Thyroid function was assessed by eight indexes, including total and free T4 and T3, Tg, TgAb, TPOAb, and TSH. A total of 2346 male participants aged ≥20 years with an average age of 50.74 ± 17.68 years were enrolled. The mean DII score among participants was −0.46 ± 1.73, ranging from −4.12 to 4.41, and mean total thyroxine (T4) was 7.61 ± 1.51 μg/dL. We found a positive association between DII and total T4 (β = 0.07; p = 0.0044). Using subgroup analysis, this association became stronger in both the iodine-deficient and obese group (iodine-deficient group: β = 0.15, p < 0.0001; obese group: β = 0.14, p < 0.0001). In conclusion, men adhering to a more pro-inflammatory diet appeared to have higher total T4 levels. However, these hormone variations were still within the normal clinical range and more well-designed studies are still needed to validate the causal relationship between DII and thyroid function.

Leydig cells are the main endogenous testosterone synthesis cells in the body. Testosterone is an essential hormone in males that affects metabolism, emotion, and pubertal development. However, little is known about the development of Leydig cells and relationship between fetal Leydig cells (FLCs) and adult Leydig cells (ALCs). The aims of this study were to investigate the effect of (FLCs) on ALC development. Our study showed that FLCs in neonatal rat testis can be eliminated by 100 mg/kg ethane dimethane sulfonate (EDS) treatment without affecting the health of newborn rats. Immunohistological results showed that eliminating FLCs led to early re-generation of the ALC population (progenitor Leydig cells [PLCs] and ALCs) accompanied at first by increased and then by decreased serum testosterone, indicating that ALCs which appeared after neonatal EDS treatment were degenerated or had attenuated functions. Our results showed that FLCs were eliminated 4 days after EDS treatment, the ALC population regenerated by 21 days, and serum testosterone levels dramatically decreased at 56 days. Collectively, our results indicate that the ablation of FLCs in neonatal rat results in abnormal development of ALCs. Our study further indicates that abnormal development of Leydig cells in the fetal stage leads to steroid hormone disorders, such as testosterone deficiency, in the adult stage. Therefore, studies of Leydig cell development are important for understanding the pathogenesis of testosterone deficiency or pubertas praecox.