Male Reproductive System Research Articles

Immediate and long-term consequences of coronavirus disease 2019 on fertility and androgenic status of men

BACKGROUND: The new coronavirus disease 2019 (COVID-19) recognized as a global pandemic, impacts many human organs and systems. In view of the coronavirus widespread and high incidence of the disease in young men of reproductive potential, It would be relevant to assess the immediate and long-term consequences of coronavirus disease on the reproductive system of men and their hormonal status AIM: To study of the effect of COVID-19 on the male reproductive system and hormonal status. MATERIALS AND METHODS: The study included the findings of examination and treatment of 62 men aged 22 to 45 years (mean age: 38.3 ± 3.2 years) who had COVID-19 confirmed by PCR testing within 3-6 months prior to the study. Sixteen (25.8%) men had severe disease, and 46 (74.2%) men suffered from moderate one. All patients enrolled in the study had spermogram parameters, mixed antiglobulin reaction (MAR) test findings and total plasma testosterone levels were within the reference values before the disease. These parameters were determined for all patients after recovery at 6 and 12 months. RESULTS: Six months after the disease, significant spermatogenesis disorders, manifested by a decreasing concentration and/or mobility and/or the number of normal forms of spermatozoa, leukospermia, were observed in 14 of 16 (87.5%) patients in the severe disease group and in 16 of 46 (34.7%) patients with moderate severity disease (p 0.05). Total plasma testosterone levels were decreased in all 16 (100%) patients in the severe group and in 32 of 46 (69.6%) patients in the moderate group (p 0.05). Within 12 months after the disease, significant disorders in the main spermogram parameters were observed in 5 of 16 (31.2%) patients with severe coronavirus disease, and in 4 of 46 (8.7%) patients with moderate coronavirus (p 0.05). A decrease in total plasma testosterone levels occurred in 10 of 16 (62,5%) men of the severe disease group and in 4 of 46 (8.7%) men with moderate disease (p 0.05). CONCLUSIONS: Our findings demonstrate the negative impact of COVID-19 on male fertility and hormonal status. The coronavirus severity mainly determines the rate, intensity and duration of spermatogenesis disorders and hypogonadism manifestations that occur after it.

Aflatoxin Exposure-Caused Male Reproductive Toxicity: Molecular Mechanisms, Detoxification, and Future Directions

Widespread endocrine disorders and infertility caused by environmental and food pollutants have drawn considerable global attention. Aflatoxins (AFTs), a prominent class of mycotoxins, are recognized as one of the key contributors to environmental and food contamination. Aflatoxin B1 (AFB1) is the most potent and toxic pollutant among them and is known to cause multiple toxic effects, including neuro-, nephro-, hepato-, immune-, and genotoxicity. Recently, concerns have been raised regarding AFB1-induced infertility in both animals and humans. Exposure to AFB1 can disrupt the structure and functionality of reproductive organs, leading to gametogenesis impairment in males, subsequently reducing fertility. The potential molecular mechanisms have been demonstrated to involve oxidative stress, cell cycle arrest, apoptosis, inflammatory responses, and autophagy. Furthermore, several signaling pathways, including nuclear factor erythroid 2-related factor 2; NOD-, LRR-, and pyrin domain-containing protein 3; nuclear factor kappa-B; p53; p21; phosphoinositide 3-kinase/protein kinase B; the mammalian target of rapamycin; adenosine 5′-monophosphate-activated protein kinase; and mitochondrial apoptotic pathways, are implicated in these processes. Various interventions, including the use of small molecules, Chinese herbal extracts, probiotic supplementation, and camel milk, have shown efficacy in ameliorating AFB1-induced male reproductive toxicity, by targeting these signaling pathways. This review provides a comprehensive summary of the harmful impacts of AFB1 exposure on male reproductive organs in mammals, highlighting the potential molecular mechanisms and protective agents.

Age-related testosterone decline: mechanisms and intervention strategies.

Contemporary societies exhibit delayed reproductive age and increased life expectancy. While the male reproductive system demonstrates relatively delayed aging compared to that of females, increasing age substantially impacts its function. A characteristic manifestation is age-induced testosterone decline. Testosterone, a crucial male sex hormone, plays pivotal roles in spermatogenesis and sexual function, and contributes significantly to metabolism, psychology, and cardiovascular health. Aging exerts profound effects on the hypothalamic-pituitary-gonadal axis and Leydig cells, precipitating testosterone reduction, which adversely affects male health. Exogenous testosterone supplementation can partially ameliorate age-related testosterone deficiency; however, its long-term safety remains contentious. Preserving endogenous testosterone production capacity during the aging process warrants further investigation as a potential intervention strategy.

Protective effects of Juglans regia oil on lead acetate-induced reprotoxicity in rats: an antioxidant, histological and computational molecular study.

Lead (Pb) is a metal that affects many body systems, primarily the male reproductive system. This study aimed to examine the phytochemical profiling and beneficial effects of Juglans regia oil (JRO) in alleviating lead-induced reprotoxicity-associated oxidative injury in rats. Adult male Wistar rats were randomly divided into four groups as follows: control group received no treatment, Pb group was exposed to 0.344 g kg-1 bw of Pb acetate, Pb + JRO group was co-treated with Pb plus walnut oil (0.9 g kg-1 bw) and JRO group received walnut oil only. Pb-treated rats showed significantly decreased gonado-somatic index, count and viability of sperm. Testosterone levels decreased in Pb-treated animals. Besides, Pb disrupted the oxidative/antioxidative status, the plasmatic lipase activity and testicular Pb content. Furthermore, Pb produced testis histopathological features, especially cell degeneration, atrophy and tubular disarrangement. Co-treatment with JRO was found to be effective for recovering the increased testicular oxidative damage-associated histological features in the Pb group. This was supported by the in silico modeling results. The in silico analyses revealed that JRO compounds bound androgen receptor and RAC-alpha serine/threonine kinase with high affinities, which together with pharmacokinetic properties and molecular interactions satisfactorily support the beneficial in vivo findings in the Pb + JRO group of rats. © 2024 Society of Chemical Industry.

Progress in the study of toxic effects of drugs on the male reproductive system

This paper provides a comprehensive summary of the toxic effects of drugs on the male reproductive system, with a special focus on the mechanisms of testicular and sperm damage caused by chemotherapeutic agents, antibiotics, and immunosuppressants. Drug-induced reproductive toxicity usually manifests through multiple pathways including direct injury, interference with hormone regulation, oxidative stress, and DNA damage. These mechanisms can lead to impaired spermatogenesis, decreased testicular function, and long-term infertility, thereby seriously affecting male reproductive health. Specifically, chemotherapeutic drugs, such as cisplatin and cyclophosphamide, have been widely documented to cause direct damage to the testes, leading to significant decreases in sperm quantity and quality. Antibiotics and nonsteroidal anti-inflammatory drugs also negatively affect reproductive function by affecting mitochondrial function and inducing oxidative stress in the testicular cells. Although important advances have been made in recent years in the study of drug-induced reproductive toxicity, further exploration is needed to assess the variability of individual responses to drugs and develop long-term protective measures. Future research should focus on developing accurate toxicity assessment methods, customized therapeutic regimens, and enhanced fertility protection strategies, such as the use of antioxidants and methods for the cryopreservation of testes and sperm. Interdisciplinary collaboration will provide new solutions for balancing disease treatment and fertility preservation, especially in the use of high-risk drugs, such as anticancer therapies, where achieving both efficacy and reproductive health will be an important clinical challenge.

Subchronic elevation in ambient temperature drives alterations to the sperm epigenome and accelerates early embryonic development in mice

Forecasted increases in the prevalence and severity of extreme weather events accompanying changes in climatic behavior pose potential risk to the reproductive capacity of humans and animals of ecological and agricultural significance. While several studies have revealed that heat stress induced by challenges such as testicular insulation can elicit a marked negative effect on the male reproductive system, and particularly the production of spermatozoa, less is known about the immediate impact on male reproductive function following subchronic whole-body exposure to elevated ambient temperature. To address this knowledge gap, we exposed unrestrained male mice to heat stress conditions that emulate a heat wave (daily cycle of 8 h at 35 °C followed by 16 h at 25 °C) for a period of 7 d. Neither the testes or epididymides of heat-exposed male mice exhibited evidence of gross histological change, and similarly, spermatozoa of exposed males retained their functionality and ability to support embryonic development. However, the embryos generated from heat-exposed spermatozoa experienced pronounced changes in gene expression linked to acceleration of early embryo development, aberrant blastocyst hatching, and increased fetal:placental weight ratio. Such changes were causally associated with an altered sperm small noncoding RNA (sncRNA) profile, such that these developmental phenotypes were recapitulated by microinjection of wild-type embryos sired by control spermatozoa with RNAs extracted from heat-exposed spermatozoa. Such data highlight that even relatively modest excursions in ambient temperature can affect male reproductive function and identify the sperm sncRNA profile as a particular point of vulnerability to this imposed environmental stress.

Coexistence of complete intestinal tract, prostatic tissue, prostatic urethra and bladder structure in ovarian mature cystic teratoma: a case report.

Mature cystic teratomas (MCTs) of the ovary comprise tissues from all three germ layers. The coexistence of the complete intestinal tract, prostatic tissue, and bladder component within the same ovarian MCT is unprecedented. Here, we report the diagnosis and management of such a rare case. A 26-year-old woman presented with a right ovarian mass, which was later confirmed as an MCT by histopathological examination. The patient underwent a successful laparoscopic cystectomy with no evidence of malignancy or postoperative complications. Histological examination revealed that this MCT contained the complete organ structures including a lower intestinal tract and male genital tract with prostate, urethra, and bladder components, which is unusual. This case underscores the importance of understanding the pathogenesis of extensive organogenesis in MCTs and raises questions about the differentiation processes leading to such unique presentations.

Effects of substance exposure on gametes and pre-implantation embryos: a narrative review.

Substance use refers to the consumption of drugs that have varying degrees of impact on a persons' physical, mental and emotional well-being. While the adverse health effects of drugs have been extensively documented, further research is needed to understand their impact on fertility. Studies have indicated that substance use affects both the male and female reproductive systems. As substance use is more prevalent among young adults compared with the elderly, it appears that individuals of reproductive age are particularly vulnerable to the reproductive impairments associated with substance use. Although numerous studies have reported detrimental effects of substance use on pregnant women and their foetus during the post-implantation stages, there are limited studies on critical pre-implantation period and gamete stages. In this narrative review, we aimed to focus on the most significant evidence regarding the impact of substances on gametes and pre-implantation embryos.

Comparative study in distal hypospadias repair: a meatal-based flaps technic vs. tubularized incised plate urethroplasty.

Hypospadias is the most common anomaly of the male genital system after undescended testis. More than 200 surgical repair techniques have been described for the treatment of hypospadias due to many different meatus localisations and other accompanying anomalies. Kutlay defined a new technique in 2010 with 10 patients with distal hypospadias patients. We compared this new technique with tubularized incised plate urethroplasty (TIP) which is one of the most frequently performed methods. 148 patients with hypospadias who underwent surgery at the Urology and Pediatric Surgery Clinic during the period of January 2010 to December 2022 in the first and 2nd clinic, were retrospectively analyzed. The study focused on the remaining 83 patients with distal hypospadias for the purpose of comparison. The mean age of group one was 10.0 (± 6.9, range 2-27), while for group two it was 10.8 (± 5.9, range 3-23). There was no statistically significant difference between the two groups in terms of anatomical position of the meatus, stricture and fistula complications (p > 0.5). The Kutlay technique has been described as an easy-to-learn and feasible method with reliable results. No significant difference in complications was observed in this study compared with TIP, which is known as the standard technique worldwide. We would like to suggest that the method be considered for further evaluation with larger patient groups and different techniques.

Susceptibility of Human Spermatozoa to Titanium Dioxide Nanoparticles: Evaluation of DNA Damage and Biomarkers

Nowadays, developing countries have seen a reduction in male reproductive parameters, and it has been linked to the exposure of endocrine disrupting chemicals (EDCs), which are able to mimic or disrupt steroid hormone actions. Also, nanoparticles have shown effects on the male reproductive system, in particular the use of TiO2-NPs in drugs, cosmetics, and food as pigment additives, and, thanks to their small size (1–100 nm), provide themselves the opportunity to be internalized by the body and pass the blood–testis barrier (BTB). Therefore, TiO2-NPs can act on spermatogenesis and spermatozoa. In this study, we carried out an in vitro assay on human spermatozoa to evaluate the effects of TiO2-NPs at the concentrations of 500, 250, 100, and 50 ppm. Exposure did not statistically alter sperm parameters (e.g., motility and viability) but induced damage to sperm DNA and the expression of biomarkers by spermatozoa. This immunofluorescence investigation showed a positivity for biomarkers of stress (HSP70 and MTs) on the connecting piece of spermatozoa and also for sex hormone binding globulin (SHBG) biomarkers. The SHBG protein acts as a carrier of androgens and estrogens, regulating their bioavailability; therefore, its expression in the in vitro assay did not rule out the ability of TiO2-NPs to act as endocrine disruptors.

Shear stress effects on epididymal epithelial cell via primary cilia mechanosensory signaling.

Shear stress, resulting from fluid flow, is a fundamental mechanical stimulus affecting various cellular functions. The epididymis, essential for sperm maturation, offers a compelling model to study the effects of shear stress on cellular behavior. This organ undergoes extensive proliferation and differentiation until puberty, achieving full functionality as spermatozoa commence their post-testicular maturation. Although the mechanical tension exerted by testicular fluid is hypothesized to drive epithelial proliferation and differentiation, the precise mechanisms remain unclear. Here we assessed whether the responsiveness of the epididymal cells to shear stress depends on functional primary cilia by combining microfluidic strategies on immortalized epididymal cells, calcium signaling assays, and high-throughput gene expression analysis. We identified 97 genes overexpressed in response to shear stress, including early growth response (Egr) 2/3, cellular communication network factor (Ccn) 1/2, and Fos proto-oncogene (Fos). While shear stress triggered a rapid increase of intracellular Ca2+, this response was abrogated following the impairment of primary ciliogenesis through pharmacological and siRNA approaches. Overall, our findings provide valuable insights into how mechanical forces influence the development of the male reproductive system, a requisite to sperm maturation.

Gene expression of tight junctions in foreskin is not affected by HIV pre-exposure prophylaxis

IntroductionTight junctions (TJs) serve as permeability filters between the internal and external cellular environment. A large number of proteins have been identified to be localized at the TJs. Due to limitations in tissue collection, TJs in the male genital tract have been understudied.MethodsWe analysed the transcriptomics of 132 TJ genes in foreskin tissue of men requesting voluntary medical male circumcision (VMMC) and enrolled in the Combined HIV Adolescent Prevention Study (CHAPS) trial conducted in South Africa and Uganda (NCT03986970). The trial evaluated the dose requirements for event-driven HIV pre-exposure prophylaxis (PrEP) with emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during insertive sex. A total of 144 participants were randomized to either control arm or one of 8 PrEP arms (n=16/arm), receiving oral FTC-TDF or FTC-TAF over one or two days. Following in vivo oral PrEP dosing and VMMC, the expression level of three important TJ proteins (CLDN-1, OCN and ZO-1) was measured ex vivo in foreskin tissue by Western blot. The expression of cytokine genes implicated in TJ regulation was determined. Non-parametric Kruskal-Wallis tests were used to compare TJ gene expression and protein levels by type of PrEP received, and Spearman’s correlation coefficients were calculated to assess whether TJ gene expression levels were related to cytokine gene levels or to PrEP drug concentrations and their active intracellularly phosphorylated metabolites.ResultsA high level of expression in foreskin tissue was found for 118 (of 132) TJ genes analysed; this finding contributed to create a map of TJ components within the male genital tract. Importantly, PrEP regimens tested in the CHAPS trial did not affect the expression of TJ genes and the analysed proteins in the foreskin; thus, further supporting the safety of this prevention strategy against HIV-1 transmission during insertive sex. Additionally, we identified the level of several cytokines’ genes to be correlated to TJ gene expression: among them, IL-18, IL-33 and VEGF.DiscussionTJs can limit viral entry into target cells; to affect this biological function viruses can reduce the expression of TJ proteins. Our study, on the expression and regulation of TJs in the foreskin, contribute important knowledge for PrEP safety and further design of HIV-1 prophylaxis.

Ginkgo biloba extract alleviates deltamethrin-induced testicular injury by upregulating SKP2 and inhibiting Beclin1-independent autophagy

BackgroundMale infertility is a worldwide concern that is associated with a decline in sperm quality. Environmental pollutants such as deltamethrin (DM) have harmful effects on male reproductive organs. By maintaining intracellular redox homeostasis, ginkgo biloba extract (GBE) can alleviate male reproductive dysfunction. However, research on the mechanisms by which GBE alleviates reproductive toxicity induced by DM is limited. PurposeIn this study, we investigated whether GBE can alleviate DM-induced testicular and Sertoli cell reproductive toxicity by modulating SKP2 and Beclin1, thus providing a theoretical basis for the development of novel therapeutic approaches. Study DesignWe explored the role of GBE in mitigating DM-induced testicular damage, with a specific focus on the intricate involvement of ubiquitination and autophagy. MethodsAn experimental model was constructed using ICR male mice and the TM4 cell line. Tissue, cellular, and sperm morphological changes were observed through methods such as Hematoxylin and Eosin (H&E) staining, Periodate-Schiff (PAS) staining, ultrastructural observation, immunohistochemistry, and immunofluorescence. Enzyme and hormone levels were measured, and gene and protein levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting techniques. ResultsIn vivo experiments showed that DM exposure led to decreased sex hormone levels, increased seminiferous tubule diameter and impaired spermatogenesis. Meanwhile, DM exposure was found to decrease ubiquitination levels, leading to mitochondrial damage and further escalation of mitochondrial autophagy. Furthermore, in the DM-induced cell model, the upregulation of Beclin1 expression was associated with the inhibition of the ubiquitin‒proteasome system (UPS) and SKP2, thereby exacerbating autophagy. However, GBE has demonstrated notable efficacy in alleviating the reproductive toxicity induced by DM. ConclusionOur findings highlighted that SKP2 is a key regulator of Beclin1-independent autophagy and that GBE exerts therapeutic effects by upregulating SKP2 and inhibiting Beclin1 activation, which ameliorates autophagy and reduces DM-induced testicular damage.

New insights into the mechanisms underlying 5-hydroxymethylfurfural-induced suppression of testosterone biosynthesis in vivo and in vitro

5-hydroxymethylfurfural (HMF), produced by the Maillard reaction, can indicate thermal processes in food. Previous research has examined the cytotoxic, genotoxic, mutagenic, and carcinogenic characteristics of HMF and its derivatives in different organs. Nevertheless, there is currently no available evidence about the impact of HMF on male reproductive toxicity. In this study, the effects of HMF on testosterone biosynthesis in both mouse testis and TM3 Leydig cells were investigated. HMF was administered to mice at doses of 30 and 300 mg/kg/day for 21 days and to Leydig cells at concentrations of 0.1, 1, and 10 mM for 24 h. The mechanism of action of HMF on testosterone biosynthesis in both mouse testis and Leydig cells was revealed by measuring the amount of testosterone, 3′,5′-cyclic adenosine monophosphate (cAMP) levels, and the expression level of some important genes in the steroidogenic pathway. In addition, its effects on general testis were examined through histopathological evaluations. Upon examination of the results, it was observed that HMF had a significant impact on reducing testosterone and cAMP levels. Furthermore, HMF inhibited the expression of steroidogenic genes, including steroidogenic acute regulatory protein, cholesterol side-chain cleavage enzyme, 3β-hydroxy dehydrogenase, and 17β-hydroxy dehydrogenase, as well as transcription factors, such as steroidogenic factor-1, GATA binding protein-4, and nerve growth factor IB. HMF-administrated groups had germinal epithelium degradation, vacuolization, and disorders in the interstitial area. Consequently, it has been proven for the first time that HMF can damage the male reproductive system by detrimentally impacting the production of testosterone.

Protective Role of Sphingosine-1-Phosphate During Radiation-Induced Testicular Injury

The impact of ionizing radiation on the male reproductive system is gaining increasing attention, particularly when it comes to testicular damage, which may result in decreased sperm quality and hormonal imbalances. Finding effective protective measures to mitigate testicular damage caused by radiation has become a focal point in the biomedical field. S1P, an essential biological signaling molecule, has garnered significant interest due to its multiple roles in regulating cellular functions and its protective effects against radiation-induced testicular injury. S1P not only effectively reduces the generation of ROS induced by radiation but also alleviates oxidative stress by enhancing the activity of antioxidant enzymes. Furthermore, S1P inhibits radiation-induced cell apoptosis by regulating the expression of anti-apoptotic and pro-apoptotic proteins. Additionally, S1P alleviates radiation-induced inflammation by inhibiting the production of inflammatory factors, thereby further protecting testicular tissue. In summary, S1P effectively reduces radiation-induced testicular damage through multiple mechanisms, offering a promising therapeutic approach to safeguard male reproductive health. Future research should explore the specific mechanisms of action and clinical application potential of S1P, aiming to contribute significantly to the prevention and treatment of radiation damage.

Ferritinophagy is involved in hexavalent chromium-induced ferroptosis in Sertoli cells

Hexavalent chromium [Cr(VI)] has significant adverse effects on the environment and human health, particularly on the male reproductive system. Previously, we observed ferroptosis and autophagy in rat testicular injury induced by Cr(VI). In the present study, we focused on the association between ferroptosis and autophagy in mouse Sertoli cells (TM4) exposed to concentrations of 2.5 μМ, 5 μМ, and 10 μМ Cr(VI). Cr(VI) exposure altered mitochondrial ultrastructure; increased intracellular iron, malondialdehyde, and reactive oxygen species (ROS) levels; decreased glutathione content; increased TfR1 protein expression; and decreased GPX4, FPN1, and SLC7A11 protein expression, ultimately resulting in ferroptosis. Additionally, we observed ferritinophagy, increased expression of BECLIN1, LC3B, and NCOA4, and decreased expression of FTH1 and P62. Inhibition of autophagy and ferritinophagy via 3-MA and small interfering RNA (siRNA)-mediated silencing of NCOA4 ameliorated changes in ferritinophagy- and ferroptosis-associated protein expression, and reduced ROS levels. Rats exposed to Cr(VI) exhibited atrophy of testicular seminiferous tubules, a reduction in germ and Sertoli cells, and the occurrence of ferritinophagy and ferroptosis in cells of the rat testes. These results indicate that ferroptosis, triggered by NCOA4-mediated ferritinophagy, is one of the mechanisms that contribute to Cr(VI)-induced damage in Sertoli cells.

Environmental Pollution and Oxidative Stress: Health Effects During Pregnancy: A Review

Oxidative stress is an imbalance between reactive oxygen species production and antioxidant defense that can lead to reproductive disorders and poor pregnancy outcomes. Environmental pollution under climate change is involved in reactive oxygen species formation and may cause various dysfunctions of the reproductive system. Oxidative stress is a widespread factor that affects the physiology of the male and female reproductive systems, leading to high levels of DNA damage and infertility. Miscarriage, preeclampsia, and premature birth are all linked to oxidative stress. Environmental pollution induces excesses of oxidative stress by expanding ROS generation or overwhelming the physiological responses of the antioxidant defense system. This increases cellular damage, inflammation, and the development of numerous diseases. Here, we present a brief outline of the physiological and developmental roles that oxidative stress plays during pregnancy. We also offer some insights into the underlying mechanisms that have been put forth, which culminate in a summary of the harmful effects of oxidative stress that have an environmental origin in pregnancy-related complications. The current work may motivate the design of more focused wellbeing measures in order to prevent and promote human health and anticipate unfavorable pregnancy outcomes.

The Impact of Neonicotinoid Pesticides on Reproductive Health.

Neonicotinoids are some of the most widely used insecticides in the world because they broadly target chewing and sucking insects. Neonicotinoids are used in commercial agricultural systems, sold for use in home gardens, and found in veterinary pharmaceuticals in the form of flea and tick preventatives for companion animals. They are also used as crop seed treatments and spread throughout crops as they mature. As a result, humans, wildlife, livestock, and pets are routinely exposed to neonicotinoids through consumption of contaminated food and water as well as through use of some veterinary pharmaceuticals. Although several studies indicate that neonicotinoid exposure causes genotoxicity, neurotoxicity, hepatotoxicity, and immunotoxicity in some non-target species, the impact of neonicotinoid pesticides on the male and female reproductive systems in mammals is largely understudied. This review summarizes current insights on the impact of common neonicotinoid pesticides such as acetamiprid, clothianidin, imidacloprid, and thiacloprid on male and female reproductive health in mammals. The review also summarizes the impacts of exposure to mixtures of neonicotinoids on reproductive endpoints. In addition, this review highlights where gaps in research on neonicotinoid pesticides and reproductive health exist so that future studies can be designed to fill current gaps in knowledge.

Low protein uptake during peripuberty impairs the testis, epididymis, and spermatozoa in pubertal and adult Wistar rats.

Protein malnutrition during critical periods poses significant risks to reproductive health. Thus, this study aims to evaluate the immediate and delayed effects of a 30-day low-protein diet on the postnatal development of the male reproductive system. For so, male rats were fed a protein-deficient diet from postnatal day 30-60, followed by evaluations of testis, epididymis, and spermatozoa both at the end of the diet and after a 60-day recovery period. Testicular and epididymal weight was lowered in pubertal animals. Several histological alterations were found in the testis, such as acidophilic cells and vacuoles in the seminiferous epithelium, and sperm production was compromised. In the epididymis, the luminal compartment was diminished, and the stroma was enlarged both in the caput and cauda; in the cauda, the epithelial compartment was enlarged; the transit time of spermatozoa through this organ was diminished. Testosterone production was lowered. Spermatozoa's motility, mitochondrial activation, and acrosomal integrity were impaired, and several alterations in morphology were observed. After the recovery period, testicular and epididymal weight was restored. Tissue remodulation was observed in the epididymis, but the spermatozoa's transit time in this organ was not altered. Sperm and testosterone production, spermatozoa motility, mitochondrial activation, and acrosomal integrity were also restored. However, testicular histological alterations and spermatic morphological abnormalities were maintained in protein-restricted animals. Protein restriction during peripuberty impairs the reproductive maturation of pubertal Wistar rats, impairing testicular and epididymal function, with lasting effects even after dietary correction.

Heat stress: a major threat to ruminant reproduction and mitigating strategies.

Stress is an external event or condition that puts pressure on a biological system. Heat stress is defined as the combination of internal and external factors acting on an animal to cause an increase in body temperature and elicit a physiological response. Heat stress is a set of conditions caused by overexposure to or overexertion at excess ambient temperature and leads to the inability of animals to dissipate enough heat to sustain homeostasis. Heat exhaustion, heat stroke, and cramps are among the symptoms. For the majority of mammalian species, including ruminants, heat stress has a negative impact on physiological, reproductive, and nutritional requirements. Reproductive functions, including the male and female reproductive systems, are negatively affected by heat stress. It decreases libido and spermatogenic activity in males and negatively affects follicle development, oogenesis, oocyte maturation, fertilization, implantation, and embryo-fetal development in females. These effects lead to a decrease in the rate of reproduction and financial losses for the livestock industry. Understanding the impact of heat stress on reproductive tissues will aid in the development of strategies for preventing heat stress and improving reproductive functions. Modification of the microenvironment, nutritional control, genetic development of heat-tolerant breeds, hormonal treatment, estrous synchronization, timed artificial insemination, and embryo transfer are among the strategies used to reduce the detrimental effects of heat stress on reproduction. These strategies may also increase the likelihood of establishing pregnancy in farm animals.