The use of sodium caseinate in the freezing of sheep semen.

The aim of this study was to assess the addition of 2% sodium caseinate in a commercial egg yolk-based medium in frozen ovine semen. Eight Dorper males were used for the study. The ejaculate was divided into two portions and frozen without (G1) or with the addition of 2% sodium caseinate (G2). Kinetic parameters were evaluated using CASA (computer-assisted sperm analysis), and membrane and acrosome integrity as well as oxidative stress were assessed using flow cytometry. After thawing, a thermoresistance test was conducted at time points T0 and T90. For the fertility test, 100 ewes were inseminated with semen from two rams selected based on in vitro parameters, one with good post-thaw quality (+70% total motility) and the other with low post-thaw quality (-55% total motility). For the fertility test, the females were divided into 4 groups for insemination: low-quality ram without caseinate (GBS = 25) and with caseinate (GBC = 25), and high-quality ram without caseinate (GAS = 25) and with caseinate (GAC = 25). Regarding the results of sperm kinetics, there was a statistically significant difference in the parameters of average path velocity (VAP) and curvilinear velocity (VCL) between the group frozen with BotuBov and the group with added caseinate. At time point T90, straight-line velocity maintained a trend (p < .06), with BotuBov® (BB group) being superior to caseinate this time, and in the linearity parameter, caseinate was superior to BotuBov®. Flow cytometry analysis showed no difference between any of the evaluated tests. In the fertility test, there was no statistically significant difference in the pregnancy rate between the BotuBOV® group (23%, 11/48) and the sodium caseinate group (BC group) (33%, 17/52), and no differences were observed in the male versus diluent interaction (p = .70). In conclusion, sodium caseinate supplementation did not influence sperm kinetic parameters and the fertility of sheep.

Reversible effects on female rat fertility with abrocitinib, a Janus kinase 1 inhibitor.

BACKGROUND: Abrocitinib is a Janus kinase (JAK) 1 selective inhibitor approved for the treatment of atopic dermatitis. Female reproductive tissues were unaffected in general toxicity studies, but an initial female rat fertility study resulted in adverse effects at all doses evaluated. A second rat fertility study was conducted to evaluate lower doses and potential for recovery. METHODS: This second study had 4 groups of 20 females each administered abrocitinib (0, 3, 10, or 70 mg/kg/day) 2 weeks prior to cohabitation through gestation day (GD) 7. In addition, 2 groups of 20 rats (0 or 70 mg/kg/day) were dosed for 3 weeks followed by a 4-week recovery period before mating. All mated females were evaluated on GD 14. RESULTS: No effects were observed at ≤10 mg/kg/day. At 70 mg/kg/day (29x human exposure), decreased pregnancy rate, implantation sites, and viable embryos were observed. All these effects reversed 4 weeks after the last dose. CONCLUSIONS: Based on these data and literature on the potential role of JAK signaling in implantation, we hypothesize that these effects may be related to JAK1 inhibition and, generally, that peri-implantation effects such as these, in the absence of cycling or microscopic changes in nonpregnant female reproductive tissues, are anticipated to be reversible.

Impact of presynchronization and Ovsynch on early postpartum ovarian activity and fertility of dairy cows in Libya.

Background: Reproductive efficiency affects dairy cow profitability. Ovarian function in postpartum (P.P.) has been better understood using ultrasound and hormonal assays. Optimizing ovulation synchronization and carefully timing artificial insemination (TAI) can greatly enhance reproductive rates in dairy cows. Aim: This experiment was designed to investigate the reproductive performance and ovarian activity in early postpartum lactating dairy cows using the Presynch-PGF2α, Ovsynch protocol, and TAI. Methods: Randomly the cows were assigned to a control group and a treatment group, based on the chronological order of their calving date. On day 14 P.P., both groups received two cloprostenol treatments, 14 days apart. Ultrasonographic inspections were conducted on day 14 to check ovarian activity and uterine contents. On day 11, after presynchronization, cows in the treatment group were given 100 µg IM. of cystorelin, followed by a luteolytic dose of 500 µg IM., cloprostenol on day 7, and a second dose of cystorelin on day 8 (36 hours later). After the second cystorelin injection by 16-20 hours, cows were inseminated, while the control group had all cows displaying spontaneous estrus between day 0 and day 28 were artificially inseminated. Results: Ovarian activity began to improve at 82.61% on day 19 P.P., with complete recovery between days 24 and 27 P.P. The second cloprostenol injection approached, causing follicular size to reach 8.41 ± 1.04 mm. After the second injection, ovarian activity switched from follicular to luteal, with corpus luteum rates of 23.91% and 26.1%. The presynchronized PGF2α regimen significantly enhanced ovarian activity from days 19-35 P.P. Ovulation and pregnancy rates in the Ovsynch group were 54.2% and 41.7% at the first timed artificial insemination (TAI), compared to 54.5% and 31.8% in the control group. There was no significant impact between them; it was just high in the presynchronized Ovsynch group. However, the P.P. period was minimized to 47-49 days till the first AI reached a 41.7% pregnancy rate and 20.8% at the second AI, for an overall 62.5%. Conclusion: The current study concludes that presynchronization during preservice in clinically normal P.P. dairy cows reduces P.P. duration, increases ovarian activity performance, and reduces ovarian dysfunctions from day 19 to day 35 P.P., as well as improves the pregnancy rate.

Long-term effect of exposure to triethylene glycol dimethacrylate (TEGDMA) on male mouse reproduction.

Our study investigated the impact on male mouse fertility and reproduction of long-term (14 weeks) exposure to triethylene glycol dimethacrylate (TEGDMA), a co-monomer of resin-based compounds, at doses of 0.01, 0.1, 1, and 10 ppm. Test and control mice were then paired with sexually mature untreated female mice and their fertility evaluated. Females paired with males exposed to all TEGDMA doses exhibited a significant decline in pregnancy rates, and significant increases in the total embryonic resorption-to-implantation ratio, except for males exposed to 0.01 ppm TEGDMA. Males in the highest dose group (10 ppm) showed significant increases in seminal vesicle and preputial gland weights. They also had significantly higher serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) than the controls, and the 0.01 ppm dosage group for FSH levels. TEGDMA exposure resulted in notable histopathological alterations in the testis, with detachment of germ cells and shedding of germinal epithelium into the tubule lumen. These results strongly indicate that TEGDMA exposure has detrimental consequences on the reproductive abilities and functions in male mice through disruption of the standard hormonal regulation of the reproductive system, leading to changes in spermatogenesis and ultimately leading to decreased fertility.

MDR49 coding for both P-glycoprotein and TMOF transporter functions in ivermectin resistance, trypsin activity inhibition, and fertility in the yellow fever mosquito, Aedes aegypti.

This study investigated the function of the MDR49 gene in Aedes aegypti. MDR49 mutants were constructed using CRISPR/Cas9 technology; the mutation led to increased sensitivity to ivermectin (LC50: from 1.3090 mg L-1 to 0.5904 mg L-1), and a reduction in midgut trypsin activity. These findings suggest that the P-gp encoded by MDR49 confers resistance to ivermectin and impacts the reproductive function in Ae. aegypti. RNA interference technology showed that knockdown of MDR49 gene resulted in a significant decrease in the expression of VGA1 after a blood meal, as well as a decrease in the number of eggs laid and their hatching rate. LC-MS revealed that following ivermectin treatment, the MDR493d+2s/3d+2s strain larvae exhibited significantly higher drug concentrations in the head and fat body compared to the wild type. Modeling of inward-facing P-gp and molecular docking found almost no difference in the affinity of P-gp for ivermectin before and after the mutation. However, modeling of the outward-facing conformation demonstrated that the flexible linker loop between TM5 and TM6 of P-gp undergoes changes after the mutation, resulting in a decrease in trypsin activity and an increase in sensitivity to ivermectin. These results provide useful insights into ivermectin resistance and the other roles played by the MDR49 gene.

Sublethal effect and detoxifying metabolism of metaflumizone and indoxacarb on the fall armyworm, Spodoptera frugiperda.

The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith) (Lepidoptera, Noctuidae), is a highly polyphagous invasive pest that damages various crops. Pesticide control is the most common and effective strategy to control FAW. In this study, we evaluated the toxicity of metaflumizone and indoxacarb against third-instar FAW larvae using the insecticide-incorporated artificial diet method under laboratory conditions. Both metaflumizone and indoxacarb exhibited substantial toxicity against FAW, with LC50 values of 2.43 and 14.66 mg/L at 72 h, respectively. The sublethal effects of metaflumizone and indoxacarb on parental and F1 generation FAW were investigated by exposing third-instar larvae to LC10 and LC30 concentrations of these insecticides. Sublethal exposure to these two insecticides significantly shortened adult longevity, extended pupal developmental times and led to reduced pupal weight, pupation rates, and adult fecundity in the treated parental generation and F1 generation at LC10 or LC30 concentrations, in comparison to the control group. The larval developmental times were shortened in the parental generation but prolonged in the F1 generation, after being treated with sublethal concentrations of metaflumizone. Furthermore, larvae exposed to LC10 or LC30 concentrations of indoxacarb exhibited elevated activity levels of cytochrome P450 monooxygenase and glutathione S-transferase, which coincides with the observed synergistic effect of piperonyl butoxide and diethyl maleate. In conclusion, the high toxicity and negative impact of metaflumizone and indoxacarb on FAW provided significant implications for the rational utilization of insecticides against this pest.

Zinc oxide nanoparticles preserve the quality and fertility potential of rooster sperm during the cryopreservation process.

Sperm cryopreservation is one of the main methods for preserving rooster sperm for artificial insemination (AI) in commercial flocks. Yet, rooster sperm is extremely susceptible to reactive oxygen species (ROS) produced during the freezing process. Oxidative stress could be prevented by using nanoparticles containing antioxidants. The present study was conducted to investigate the effect of zinc oxide nanoparticles (ZnONP) in rooster semen freezing extender on quality parameters and fertility potential. For this aim, semen samples were collected and diluted in Lake extenders as follows: control: Lake without ZnONP, ZnO100: Lake with 100-µg zinc oxide (ZnO), ZnONP50: Lake with 50-µg ZnONP, ZnONP100: Lake with 100-µg ZnONP and ZnONP200: Lake with 200-µg ZnONP. After freezing and thawing, sperm motility, viability, membrane integrity, morphology, mitochondrial activity, acrosome integrity, DNA fragmentation, lipid peroxidation and ROS, as well as fertility and hatchability were assessed. According to the current results, higher rates of motility, membrane integrity, mitochondrial activity, acrosome integrity and live cells were detected in the ZnO100, ZnONP50 and ZnONP100 groups compared to other groups (p ≤ .05). Yet, the percentage of dead cells, DNA fragmentation, lipid peroxidation and ROS levels were lower in the mentioned groups (p ≤ .05). Furthermore, a higher percentage of fertility was observed in the ZnO100 and ZnONP100 groups than in the control group (p ≤ .05). In conclusion, the use of 100-µg ZnO and 50- to 100-µg ZnONP represents a valuable and safe additive material that could be used to improve the quality and fertility potential of rooster sperm under cryopreservation conditions.

The allostery and modification of hGHRH molecules and specific dimer produced significant fertility effect by proliferating and activating in-situ ovarian mesenchymal stem cells.

The negative coordination of growth hormone secretagogue receptor (GHS-R) and growth hormone-releasing hormone receptor (GHRH-R) involves in the repair processes of cellular injury. The allosteric U- or H-like modified GHRH dimer Grinodin and 2Y were comparatively evaluated in normal Kunming mice and hamster infertility models induced by CPA treatment. 1-3-9 µg of Grinodin or 2Y per hamster stem-cell-exhaustion model was subcutaneously administered once a week, respectively inducing 75-69-46 or 45-13-50 % of birth rates. In comparison, the similar mole of human menopausal gonadotropin (hMG) or human growth hormone (hGH) was administered once a day but caused just 25 or 20 % of birth rates. Grinodin induced more big ovarian follicles and corpora lutea than 2Y, hMG, hGH. The hMG-treated group was observed many distorted interstitial cells and more connective tissues and the hGH-treated group had few ovarian follicles. 2Y had a plasma lifetime of 21 days and higher GH release in mice, inducing lower birth rate and stronger individual specificity in reproduction as well as only promoting the proliferation of mesenchymal-stem-cells (MSCs) in the models. In comparison, Grinodin had a plasma lifetime of 30 days and much lower GH release in mice. It significantly promoted the proliferation and activation of ovarian MSCs together with the development of follicles in the models by increasing Ki67 and GHS-R expressions, and decreasing GHRH-R expression in a dose-dependent manner. However, the high GH and excessive estrogen levels in the models showed a dose-dependent reduction in fertility. Therefore, unlike 2Y, the low dose of Grinodin specifically shows low GHS-R and high GHRH-R expressions thus evades GH and estrogen release and improves functions of organs, resulting in an increase of fertility.

Melatonin protects oogenesis from hypobaric hypoxia-induced fertility damage in mice.

Environmental hypoxia adversely affects reproductive health in humans and animals at high altitudes. Therefore, how to alleviate the follicle development disorder caused by hypoxia exposure and to improve the competence of fertility in plateau non-habituated female animals are important problems to be solved urgently. In this study, a hypobaric hypoxic chamber was used for 4 weeks to simulate hypoxic conditions in female mice, and the effects of hypoxia on follicle development, proliferation and apoptosis of granulosa cells, reactive oxygen species (ROS) levels in MII oocyte and 2-cell rate were evaluated. At the same time, the alleviating effect of melatonin on hypoxic exposure-induced oogenesis damage was evaluated by feeding appropriate amounts of melatonin daily under hypoxia for 4 weeks. The results showed that hypoxia exposure significantly increased the proportion of antral follicles in the ovary, the number of proliferation and apoptosis granulosa cells in the follicle, and the level of ROS in MII oocytes, eventually led to the decline of oocyte quality. However, these defects were alleviated when melatonin was fed under hypoxia conditions. Together, these findings suggest that hypoxia exposure impaired follicular development and reduced oocyte quality, and that melatonin supplementation alleviated the fertility reduction induced by hypoxia exposure.

Fecundity decline is male derived following transfluthrin exposures in a field strain of Aedes albopictus (Diptera: Culicidae).

Volatile pyrethroids are effective in reducing mosquito populations and repelling vectors away from hosts. However, many gaps in knowledge exist for the sublethal impacts of volatile pyrethroids on mosquitoes. To that end, transfluthrin exposures were conducted on a field strain of Aedes albopictus (Skuse) held as a laboratory colony. Dose-response analysis was conducted on both sexes at either 1-4 days old or 5-10 days old. Resultant concentration data were used to evaluate the LC20 and LC50 values in various mate pairings of treatments and controls in which either the male or female was from a selectively treated group and mated with a counterpart that was treated independently. Blood feeding proportion, delayed mortality after a 24-h recovery period, egg collection totals, and F1 larval survival were determined following transfluthrin treatment in the F0, but outcomes were not significant. In contrast, sterility was predicated on male treatment, with treated females resulting in higher overall egg viability. Treated males in the mating pair resulted in significantly lower egg viability and accelerated larval hatch in the F1. Additionally, the presence of sperm in female spermathecae was significantly diminished in test groups containing treated male mosquitoes. Male sublethal effects may be a critical determinant of a mixed population's reproductive success.

Sast1-mediated manifold effects inhibit Plutella xylostella fertility.

BACKGROUND: Plutella xylostella (Linnaeus) is a destructive pest of cruciferous crops due to its strong reproductive capacity and extensive resistance to pesticides. Seminal fluid proteins (SFPs) are the main effective factors that determine the reproductive physiology and behaviour of both sexes. Although an increasing number of SFPs have been identified, the effects of astacins in SFPs on agricultural pests have not yet been reported. Here, we elucidated the mechanisms by which Sast1 (seminal astacin 1) regulates the fertility of Plutella xylostella (L.). RESULTS: PxSast1 was specifically expressed in the testis and accesssory gland. CRISPR/Cas9-induced PxSast1 knockout successfully constructed two homozygous mutant strains. Sast1 impaired the fertility of P. xylostella by separately regulating the reproductive capacity of males and females. Loss of PxSast1, on the one hand, significantly decreased the ability of males to mate and fertilize, mainly manifested as shortened mating duration, reduced mating competitiveness and decreased eupyrene sperm production; on the other hand, it significantly inhibited the expression of chorion genes in females, resulting in oogenesis deficits. Simultaneously, for mated females, the differentially expressed genes in signalling pathways related to oogenesis and chorion formation were significantly enriched after PxSast1 knockout. CONCLUSION: These analyses of the functions of PxSast1 as the regulator of spermatogenesis and oogenesis establish its importance in the fertility process of P. xylostella, as well as its potential as a promising target for genetic regulation-based pest control. © 2024 Society of Chemical Industry.

Assessing the influence of preconception diet on male fertility: a systematic scoping review.

BACKGROUND: The last decade has seen increased research on the relationship between diet and male fertility, but there are no clearly defined nutritional recommendations for men in the preconception period to support clinical fertility outcomes. OBJECTIVE AND RATIONALE: The purpose of this scoping review is to examine the extent and range of research undertaken to evaluate the effect(s) of diet in the preconception period on male clinical fertility and reproductive outcomes. SEARCH METHODS: Four electronic databases (MEDLINE and EMBASE via Ovid, CAB Direct, and CINAHL via EBSCO) were searched from inception to July 2023 for randomized controlled trials (RCTs) and observational studies (prospective/retrospective, case-control, and cross-sectional). Intervention studies in male participants or couples aiming to achieve dietary or nutritional change, or non-intervention studies examining dietary or nutritional components (whole diets, dietary patterns, food groups or individual foods) in the preconception period were included. Controls were defined as any comparison group for RCTs, and any/no comparison for observational studies. Primary outcomes of interest included the effect(s) of male preconception diet on clinical outcomes such as conception (natural or via ART), pregnancy rates and live birth rates. Secondary outcomes included time to conception and sperm parameters. OUTCOMES: A total of 37 studies were eligible, including one RCT and 36 observational studies (prospective, cross-sectional, and case-control studies; four studies in non-ART populations) published between 2008 and 2023. Eight reported clinical outcomes, 26 reported on secondary outcomes, and three reported on both. The RCT did not assess clinical outcomes but found that tomato juice may benefit sperm motility. In observational studies, some evidence suggested that increasing fish or reducing sugar-sweetened beverages, processed meat or total fat may improve fecundability. Evidence for other clinical outcomes, such as pregnancy rates or live birth rates, showed no relationship with cereals, soy and dairy, and inconsistent relationships with consuming red meat or a 'healthy diet' pattern. For improved sperm parameters, limited evidence supported increasing fish, fats/fatty acids, carbohydrates and dairy, and reducing processed meat, while the evidence for fruits, vegetables, cereals, legumes, eggs, red meat and protein was inconsistent. Healthy diet patterns in general were shown to improve sperm health. WIDER IMPLICATIONS: Specific dietary recommendations for improving male fertility are precluded by the lack of reporting on clinical pregnancy outcomes, heterogeneity of the available literature and the paucity of RCTs to determine causation or to rule out reverse causation. There may be some benefit from increasing fish, adopting a healthy dietary pattern, and reducing consumption of sugar-sweetened beverages and processed meat, but it is unclear whether these benefits extend beyond sperm parameters to improve clinical fertility. More studies exploring whole diets rather than singular foods or nutritional components in the context of male fertility are encouraged, particularly by means of RCTs where feasible. Further assessment of core fertility outcomes is warranted and requires careful planning in high-quality prospective studies and RCTs. These studies can lay the groundwork for targeted dietary guidelines and enhance the prospects of successful fertility outcomes for men in the preconception period. Systematic search of preconception diet suggests that increasing fish and reducing sugary drinks, processed meats and total fat may improve male fertility, while consuming healthy diets, fish, fats/fatty acids, carbohydrates and dairy and reducing processed meat can improve sperm health.

Association of living environmental and occupational factors with semen quality in chinese men: a cross-sectional study.

Sperm quality can be easily influenced by living environmental and occupational factors. This study aimed to discover potential semen quality related living environmental and occupational factors, expand knowledge of risk factors for semen quality, strengthen men's awareness of protecting their own fertility and assist the clinicians to judge the patient's fertility. 465 men without obese or underweight (18.5 < BMI < 28.5 kg/m2), long-term medical history and history of drug use, were recruited between June 2020 to July 2021, they are in reproductive age (25 < age < 45 years). We have collected their semen analysis results and clinical information. Logistic regression was applied to evaluate the association of semen quality with different factors. We found that living environment close to high voltage line (283.4 × 106/ml vs 219.8 × 106/ml, Cohen d = 0.116, P = 0.030) and substation (309.1 × 106/ml vs 222.4 × 106/ml, Cohen d = 0.085, P = 0.015) will influence sperm count. Experienced decoration in the past 6 months was a significant factor to sperm count (194.2 × 106/ml vs 261.0 × 106/ml, Cohen d = 0.120, P = 0.025). Living close to chemical plant will affect semen PH (7.5 vs 7.2, Cohen d = 0.181, P = 0.001). Domicile close to a power distribution room will affect progressive sperm motility (37.0% vs 34.0%, F = 4.773, Cohen d = 0.033, P = 0.030). Using computers will affect both progressive motility sperm (36.0% vs 28.1%, t = 2.762, Cohen d = 0.033, P = 0.006) and sperm total motility (57.0% vs 41.0%, Cohen d = 0.178, P = 0.009). After adjust for potential confounding factors (age and BMI), our regression model reveals that living close to high voltage line is a risk factor for sperm concentration (Adjusted OR 4.03, 95% CI 1.15-14.18, R2 = 0.048, P = 0.030), living close to Chemical plants is a protective factor for sperm concentration (Adjusted OR 0.15, 95% CI 0.05-0.46, R2 = 0.048, P = 0.001) and total sperm count (Adjusted OR 0.36, 95% CI 0.13-0.99, R2 = 0.026, P = 0.049). Time spends on computer will affect sperm total motility (Adjusted OR 2.29, 95% CI 1.11-4.73, R2 = 0.041, P = 0.025). Sum up, our results suggested that computer using, living and working surroundings (voltage line, substation and chemical plants, transformer room), and housing decoration may association with low semen quality. Suggesting that some easily ignored factors may affect male reproductive ability. Couples trying to become pregnant should try to avoid exposure to associated risk factors. The specific mechanism of risk factors affecting male reproductive ability remains to be elucidated.

[Fertility and fertility preservation in women]. / Fertilität und Fertilitätserhalt der Frau.

BACKGROUND: Advances in the treatment of cancer and in reproductive medicine make it possible for many patients to start their family planning even after cytotoxic therapy. Depending on the age of the patient, the planned oncological therapy and its urgency, various methods can be used to preserve the fertility of affected women. OBJECTIVES: Presentation of facts about fertility, as well as information about fertility-preserving methods for women, so that they can be discussed with and offered to patients. MATERIALS AND METHODS: Presentation and discussion of basic research, clinical data, and expert recommendations on fertility and fertility preservation. RESULTS: Well-established fertility-protective techniques now exist for women that offer a realistic chance of subsequent pregnancy. These include transposition of the gonads prior to radiotherapy, gonadal protection with gonadotropin-releasing hormone (GnRH) analogues and cryopreservation of fertilized and unfertilized oocytes, as well as cryopreservation of ovarian tissue. CONCLUSIONS: Fertility-protective techniques are an integral part of oncological treatments for prepubertal girls and patients of reproductive age. The various measures must be discussed individually with the patient as part of a multimodal concept. Prompt and timely collaboration with a specialized center is essential.

The investigation of the effects of vitamin A, vitamin E, and ß-carotene plus vitamin E on some fertility parameters in ewes.

This study was aimed at investigating the effects of vitamin A (VITA), vitamin E (VITE), and combined ß-carotene plus vitamin E (ßCAR+VITE) injections on some fertility parameters in ewes. Estrus synchronization was performed by treating the ewes with intravaginal FGA sponges impregnated with 30 mg of fluorogestone acetate. On the days of the insertion and withdrawal of the intravaginal sponges, groups VITA, VITE, and ßCAR+VITE were administered with 500 000 IU of vitamin A, 50 mg of vitamin E, and a combination of ß-carotene plus vitamin E, respectively. The ewes in the control group (C) were maintained for control purposes. Statistically significant differences were determined between groups VITA and ßCAR+VITE, groups VITE and ßCAR+VITE, and groups C and ßCAR+VITE, as well as groups VITE and C, groups VITA and C for the multiple birth rates. While significant differences were determined between groups VITA and C, groups VITE and C, and groups ßCAR+VITE and C for the lambing rates, it was ascertained that the ratio of newborn lambs to delivered ewes (litter size) significantly differed between groups VITA and ßCAR+VITE, groups VITA and C, groups VITE and ßCAR+VITE, groups VITE and C, and groups ßCAR+VITE and C. The highest MDA level and lowest GSH level were determined on day 20 after mating in the control group. In conclusion, it is suggested that both multiple birth rates and litter size can be increased by the combined administration of ß-carotene and vitamin E.

Pesticide Toxicity Associated with Infertility.

Pesticides have benefited mankind in many ways like agriculture, industrial and health sectors. On the other hand, conversely their deleterious effects in both, humans and animals are also alarming. Pesticides including organophosphates, organochlorines, carbamates, pyrethrins and pyrethroids are found sufficiently in the environment resulting in everyday human exposure. This is of a huge concern because most of the pesticides are known to target all the physiological functions of both humans and animals. Indeed, reproduction, being one of the most important physiological processes, that is affected by the daily exposure to pesticides and leading to infertility issues. The present study summarizes the exposure of men and women to certain pesticides resulting in different infertility concerns like sperm abnormalities, decreased fertility, abnormal sperm count and motility, testicular atrophy, ovarian dysfunction, spontaneous abortions, disruption of hypothalamic-pituitary-gonadal axis, etc. So, this article will be helpful in perceiving the mechanism of reproductive toxicity of different pesticides and their management before any alarm of danger.

Guía clínica de atención a menores transexuales, transgéneros y de género diverso / Clinical practice guidelines for transsexual, transgender and gender diverse minors

Algunas personas, también las menores de edad, tienen una identidad de género que no se corresponde con el sexo asignado al nacer. Se les conoce como personas trans*, que es el término paraguas que engloba transgénero, transexual y otras identidades no conformes con el género asignado. Las unidades de asistencia sanitaria a menores trans* requieren un trabajo multidisciplinario, realizado por personal experto en identidad de género, que permita, cuando así lo soliciten, intervenciones para el menor y su entorno sociofamiliar, de forma individualizada y flexible durante el camino de afirmación de género. Este modelo de servicio también incluye tratamientos hormonales adaptados en la medida de lo posible a las necesidades del individuo, más allá de los objetivos dicotómicos de un modelo binario tradicional. Esta guía aborda los aspectos generales de la atención profesional de menores trans* y presenta el protocolo actual basado en evidencia de tratamientos hormonales para adolescentes trans* y no binarios. Además, detalla aspectos clave relacionados con los cambios corporales esperados y sus posibles efectos secundarios, así como el asesoramiento previo sobre preservación de la fertilidad. (AU)

Some people, including minors, have a gender identity that does not correspond to the sex assigned at birth. They are known as trans* people, which is an umbrella term that encompasses transgender, transsexual, and other identities not conforming to the assigned gender. Healthcare units for trans* minors require multidisciplinary working, undertaken by personnel expert in gender identity, enabling, when requested, interventions for the minor and their social–familial environment, in an individualized and flexible way during the gender affirmation path. This service model also includes hormonal treatments tailored as much as possible to the individual's needs, beyond the dichotomic goals of a traditional binary model. This guide addresses the general aspects of professional care of trans* minors and presents the current evidence-based protocol of hormonal treatments for trans* and non-binary adolescents. In addition, it details key aspects related to expected body changes and their possible side effects, as well as prior counselling about fertility preservation. (AU)

Suppressive Role of Lactoferrin in Overweight-Related Female Fertility Problems.

The secretory glycoprotein lactoferrin (LF) is suggested to ameliorate overweight regardless of non-genetic or genetic mechanisms. Although maternal overweight represents a key predictor of offspring growth, the efficacy of LF on fertility problems in overweight and obese mothers remains unknown. To address this issue, we examined the effect of LF ingestion by analyzing overweight mice (Institute of Cancer Research (ICR) mice with high-fat diets; HF mice) and obese mice (leptin-deficient mice with type II diabetes; ob/ob mice). Plasma insulin, leptin, glucose, and cholesterol levels were measured, and thermal imaging and histological analysis were employed. The litter size of HF females was reduced due to miscarriage, which was reversed by LF ingestion. In addition, LF ingestion suppressed overweight prevalence in their offspring. The component analysis of the maternal blood demonstrated that glucose concentration in both HF females and their offspring was normalized by LF ingestion, which further standardized the concentration of insulin, but not leptin. LF ingestion was unable to reverse female infertility in ob/ob mice, although their obesity and uterine function were partially improved. Our results indicate that LF upregulates female fertility by reinforcing ovarian and uterine functions in females that are overweight due to caloric surplus.

Reproductive and developmental safety of nirmatrelvir (PF-07321332), an oral SARS-CoV-2 Mpro inhibitor in animal models.

Nirmatrelvir (PF-07321332; NMV) the antiviral component of PAXLOVID™ is a potent and selective inhibitor of the SARS-CoV-2 main protease (Mpro), which plays a critical role in viral replication. PAXLOVID, comprised of nirmatrelvir and ritonavir (used as a pharmacokinetic enhancer), is an oral therapy currently in development as a therapeutic option for those infected with SARS-CoV-2 to prevent progression to severe disease, hospitalization, and death. PAXLOVID has been shown to be efficacious against hospitalization and death in two Phase 2/3 clinical studies that evaluated non hospitalized patients both with and without high risk factors for progression to severe illness. Given that males and females of reproductive age are included in the intended patient population, we assessed the potential effects of NMV up to the limit dose of 1000 mg/kg/day in ICH guideline embryo-fetal development studies in rats and rabbits, and a fertility and early embryonic development study in rats. There were no effects on male and female fertility or early embryonic development in rats, and no severe manifestations of developmental toxicity in rats or rabbits. The lack of adverse findings reported here in nonclinical species is consistent with the intended therapeutic target of NMV (a virus specific protein not present in mammalian cells), the favorable off-target selectivity profile, and lack of genetic toxicity. The results of these nonclinical studies with NMV along with existing ritonavir safety information indicate that there are no clinically relevant risks associated with PAXLOVID administration during pregnancy and in males and females of reproductive age.

TrkB agonist antibody ameliorates fertility deficits in aged and cyclophosphamide-induced premature ovarian failure model mice.

Premature ovarian failure (POF) is a leading cause of women's infertility without effective treatment. Here we show that intravenous injection of Ab4B19, an agonistic antibody for the BDNF receptor TrkB, penetrates into ovarian follicles, activates TrkB signaling, and promotes ovary development. In both natural aging and cyclophosphamide-induced POF models, treatment with Ab4B19 completely reverses the reduction of pre-antral and antral follicles, and normalizes gonadal hormone. Ab4B19 also attenuates gonadotoxicity and inhibits apoptosis in cyclophosphamide-induced POF ovaries. Further, treatment with Ab4B19, but not BDNF, restores the number and quality of oocytes and enhances fertility. In human, BDNF levels are high in granulosa cells and TrkB levels increase in oocytes as they mature. Moreover, BDNF expression is down-regulated in follicles of aged women, and Ab4B19 activates TrkB signaling in human ovary tissue ex vivo. These results identify TrkB as a potential target for POF with differentiated mechanisms, and confirms superiority of TrkB activating antibody over BDNF as therapeutic agents.