Reproductive toxicology最新文献

{"title":"Determination of the zebrafish embryo developmental toxicity assessment (ZEDTA) as an alternative non-mammalian approach for the safety assessment of agrochemicals","authors":"Jonathan S. Ball ,&nbsp;Anna Tochwin ,&nbsp;Matthew J. Winter ,&nbsp;Maciej Trznadel ,&nbsp;Richard Currie ,&nbsp;Kathryn Wolton ,&nbsp;Julian M. French ,&nbsp;Malcolm J. Hetheridge ,&nbsp;Charles R. Tyler","doi":"10.1016/j.reprotox.2025.108837","DOIUrl":"10.1016/j.reprotox.2025.108837","url":null,"abstract":"<div><div>With the US Environment Protection Agency reducing requests for (and funding of) mammalian studies alongside the proposed elimination of requests by 2035, there is an urgent need for fully validated New Approach Methods (NAMs) to fill the resultant gap for safety assessment of agrochemicals. One promising NAM for assessing the potential for human prenatal developmental toxicity potential is the Zebrafish Embryo Developmental Toxicity Assessment, a bioassay that has been used by the pharmaceutical industry for more than a decade in early-stage drug safety assessment. Despite its promise, little data has been generated to assess the validity of ZEDTA for assessing Developmental and Reproductive Toxicity of new agrochemical products. Addressing this knowledge gap, we tested 67 compounds (insecticides, herbicides and fungicides) spanning multiple different chemical groupings and mechanisms of action. ZEDTA assay results were compared with the European Chemicals Agency (ECHA) Classification and Labelling (C&amp;L) for mammalian hazard classification and with publicly available data to determine the ZEDTA’s translation power. Overall, the ZEDTA assay had an effective detection capability of 65 % for sensitivity and 64 % for specificity as compared with the ECHA-C&amp;L classification and publicly available data. Comparing the ZEDTA data there were both strengths and weaknesses in alignments for across the different chemical classes and chemical mechanisms of action. Overall, the data generated, show the performance of the ZEDTA assay was comparable with other bioassays highlighted as alternatives for mammalian assessment and holds good promise as a NAM for screening agrochemical prenatal developmental toxicity during new product human safety assessment.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108837"},"PeriodicalIF":3.3,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive digital documentation of teratology studies","authors":"Josef P. Magyar,&nbsp;Roxana Simon,&nbsp;Monika Petus,&nbsp;Krisztina Rigó","doi":"10.1016/j.reprotox.2025.108838","DOIUrl":"10.1016/j.reprotox.2025.108838","url":null,"abstract":"<div><div>One of the main endpoints for the evaluation of Developmental and Reproductive Toxicology (DART) studies is the determination of potential effects of a test substance on the skeleton during foetal development. In the course of a DART study according to the OECD 414 guideline, 400–500 gestational day 20-old (GD20), alizarin red and alcian blue-stained (ARAB) rat foetuses have to be assessed by a teratology expert, which is a time consuming and sub-optimally documented process. We have developed a method which allows for a standardised, comprehensive, quick and easy to perform, head-to-toe digital documentation of ARAB-stained GD20 rat foetuses. The method consists of the acquiring a video-stream or a time lapse-recording of foetuses, which for this purpose are axially rotated in a custom-made device. The obtained digital material is suitable for the complete visual inspection of stained foetal specimen from all sides in great detail, and thus can replace the conventional inspection under a binocular microscope, and might render the archiving of such specimen unnecessary.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108838"},"PeriodicalIF":3.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term oral fluoxetine leads to reduced male reproductive function in mice and gradual recovery after discontinuation","authors":"Yingwei Chen ,&nbsp;Ying Xiong ,&nbsp;Lu Zhu ,&nbsp;Longjie Gu ,&nbsp;Yi Liu","doi":"10.1016/j.reprotox.2025.108840","DOIUrl":"10.1016/j.reprotox.2025.108840","url":null,"abstract":"<div><div>Fluoxetine, a widely used selective serotonin reuptake inhibitor (SSRI), is highly effective in treating psychiatric disorders such as depression. Recently, its potential negative impact on male reproductive function has recently raised concerns, but it remains unknown whether testicular damage from long-term fluoxetine exposure can recover after stopping the drug. In this study, male C57BL/6 mice were divided into control (saline) and treatment (fluoxetine, 20 mg/kg.d) groups, administered orally for 4 weeks. This duration and dosage have been proven to demonstrate significant antidepressant effects in mice. Fertility assessments and euthanasia was then performed at three time points: immediately after treatment cessation, 4 weeks post-discontinuation, and 8 weeks post-discontinuation (n = 8). Results found that following long-term fluoxetine administration, male mice exhibited significantly reduced mating and fertility indices, decreased sperm count and motility, and increased sperm deformities compared to the control group. Testicular histology showed immature germ cells within the seminiferous tubule lumens, along with significantly reduced seminiferous epithelial thickness, seminiferous tubule diameter, and Johnsen score. Ki67 (proliferation marker) expression decreased, while Caspase3 (apoptosis marker) increased. By 4 weeks post-discontinuation, Ki67 and Caspase3 levels in the fluoxetine-treated group returned to control levels, with partial recovery in other parameters. By 8 weeks, all measured parameters had largely normalized, indicating significant recovery in reproductive function. These findings provided novel insights into fluoxetine's reproductive toxicity and were crucial for assessing its clinical safety in drug evaluations.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108840"},"PeriodicalIF":3.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal exposure to nicotine causes oxidative stress and inflammatory changes in the ovaries of rats’ adult offspring","authors":"I.M.M. Freitas ,&nbsp;I.D. Santos ,&nbsp;J.C. Souza ,&nbsp;G.S. Souza ,&nbsp;L.W. Fischer ,&nbsp;R.A. Da Silva ,&nbsp;C.D. Gil ,&nbsp;C.C. Paccola","doi":"10.1016/j.reprotox.2025.108839","DOIUrl":"10.1016/j.reprotox.2025.108839","url":null,"abstract":"<div><div>Nicotine is one of the most toxic substances found in cigarettes, but also found in chewing tobacco gum, patches and vaping products (electronic cigarettes). In addition to being a highly addictive chemical, it is capable of reducing fertility in men and women. In the ovaries, it can induce morphological changes and impair the formation of follicles, being a possible cause of changes in the reproductive cycle and anticipation of menopause in women whose mothers smoked during pregnancy. By increasing the generation of free radicals, nicotine can induce oxidation in biological samples and change the expression of inflammatory cytokines. It damages the immune system and many other cells of newborns exposed prenatally. Despite its teratogenic potential, many women continue to use this drug during pregnancy and lactation. Thus, this work aims to analyze the effects of maternal exposure to nicotine on the ovaries of adult rats. To this end, 10 rats received nicotine throughout pregnancy and lactation. Their offspring were euthanized around 90 days-old, in the metestrus phase, for ovary collection and analysis of oxidative stress and inflammation. The results showed that exposure to nicotine increased MDA level, but did not cause damage to the DNA of ovarian cells (8-OHdG). It also increased IL-1β and anti-inflammatory protein AnxA1 and receptor Fpr1, and reduced the mast cell population in ovaries. We concluded that maternal exposure to nicotine is capable of inducing oxidative stress and leading to inflammatory changes in the ovaries of adult offspring exposed during the intrauterine and breastfeeding phases.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108839"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic fat consumption affects metabolic aspects of murine physiology and influences ovarian follicle atresia","authors":"Ayodeji Ojo Oteyola ,&nbsp;Isadora Maria Sátiro de Oliveira ,&nbsp;Jonathas Medeiros de Almeida ,&nbsp;Lucas Carvalho Cardoso ,&nbsp;Thais de Merici Domingues e Paula ,&nbsp;Julia Meireles Nogueira ,&nbsp;Jade Carceroni de Sousa Carvalho ,&nbsp;Henrique Martins Nogueira ,&nbsp;Brenda Lee Simas Porto ,&nbsp;Ana Paula Lucas Mota ,&nbsp;Paulo Henrique Almeida Campos-Junior ,&nbsp;Erika Cristina Jorge ,&nbsp;Fernanda Radicchi Campos Lobato de Almeida","doi":"10.1016/j.reprotox.2025.108836","DOIUrl":"10.1016/j.reprotox.2025.108836","url":null,"abstract":"<div><div>Saturated fat has been linked to cardiovascular diseases, leading to an increase in polyunsaturated fat consumption. The aim of the present study was to investigate the effects of three fat sources (coconut oil, lard and soybean oil) on metabolic and reproductive parameters in heterogenic mice. Female Swiss mice (5–6 weeks old; n = 9/group) were divided into four experimental groups: control (CC), coconut oil (CO), lard (LA), and soybean oil (SO), and were orally given 0.6 mL of the corresponding fat daily for 6 weeks to further investigate morphological, biochemical, and molecular parameters. SO females showed the highest glucose intolerance (P &lt; 0.05), and all experimental groups were highly insulin resistant, with no statistical differences among them (P &gt; 0.05). Moreover, all fat supplemented groups presented increased proportion in bile ducts, and CO and SO females presented higher LDL-cholesterol levels compared to CC (P &lt; 0.05). Regarding reproductive parameters, estrous cycle alterations were observed mainly in the SO group, showing extended luteal phase duration (longer diestrus), and higher numbers of atretic follicles per area compared to the CC females (P &lt; 0.05). Furthermore, higher proportion of active Casp-3 positive cells in the granulosa layers of preantral follicles were observed in the LA compared to the CO group (P &lt; 0.05). The gene expression data revealed downregulation of <em>Igf1r</em> and <em>Acvr1</em> in SO, upregulation of <em>Igf1r</em> in LA and <em>Lhcgr</em> in CO compared to CC females (P &lt; 0.05). Thus, excessive fat intake may have deleterious effects on metabolism and reproductive function, but lard may be the least harmful source.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108836"},"PeriodicalIF":3.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The associations between prenatal plastic phthalate exposure and lipid acylcarnitine levels in humans and mice","authors":"Kristina Vacy ,&nbsp;Thusi Rupasinghe ,&nbsp;Alicia Bjorksten ,&nbsp;Andrea Gogos ,&nbsp;Peter J. Meikle ,&nbsp;Satvika Burugupalli ,&nbsp;Wah Chin Boon ,&nbsp;Anne-Louise Ponsonby ,&nbsp;Barwon Infant Study Investigator Group","doi":"10.1016/j.reprotox.2025.108835","DOIUrl":"10.1016/j.reprotox.2025.108835","url":null,"abstract":"<div><div>Phthalates are ubiquitous environmental pollutants known for their endocrine-disrupting properties, particularly during critical periods such as pregnancy and early childhood. Phthalates alter lipid metabolism, but the role of prenatal exposure on the offspring lipidome is less understood. In particular, we focused on long chain acylcarnitines - intermediates of fatty acid oxidation that serve as potential biomarkers of mitochondrial function and energy metabolism. This study aimed (i) to investigate the association between prenatal phthalate exposure and the child’s blood acylcarnitine concentrations and, (ii) to evaluate the impact of prenatal administration of di-(2-ethylhexyl) phthalate (DEHP) on acylcarnitine levels in mouse offspring blood, brain and liver. We conducted analyses of both a prospective birth cohort study and an experimental study in mice. From the Barwon Infant Study cohort (1074 mother-child pairs), prenatal phthalate exposure was assessed at 36 weeks' gestation and its association with acylcarnitine levels was examined in cord blood, and child’s blood at 6 months, 12 months and 4 years. In mice, pregnant C57BL/6 J mouse dams were exposed to 20 μg/kg DEHP for 5 days mid-gestation, and offspring tissues were analyzed at 1 month of age postnatally for acylcarnitine profiles. Our findings demonstrate that prenatal phthalate levels (specifically butyl benzyl phthalate (BBzP) and diisobutyl phthalate (DiBP)) are inversely associated with total long chain acylcarnitine levels in human cord blood at birth. In contrast, BBzP was positively associated with the long chain acylcarnitines at 12 months of age. In mice, prenatal DEHP exposure for only 5 days led to decreased palmitoylcarnitine (AC16:0) levels in the brain and liver, but not in blood. Taken together, our findings highlight that prenatal phthalate exposure can alter acylcarnitine profiles, indicating disruptions in fatty acid metabolism that may have long-term effects on metabolic health.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108835"},"PeriodicalIF":3.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between dietary intake estimated levels of PCDD/Fs and human sperm quality","authors":"María Ángeles Martínez ,&nbsp;Albert Salas-Huetos ,&nbsp;María Fernández de la Puente ,&nbsp;Cristina Valle-Hita ,&nbsp;Nadine Khoury ,&nbsp;Elena Sánchez-Resino ,&nbsp;Carla Ramos-Rodríguez ,&nbsp;Estefanía Davila-Cordova ,&nbsp;Jordi Salas-Salvadó ,&nbsp;Nancy Babio","doi":"10.1016/j.reprotox.2025.108831","DOIUrl":"10.1016/j.reprotox.2025.108831","url":null,"abstract":"<div><div>This study aimed to investigate the association between estimated dietary intake of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) and human sperm quality. This study cross-sectionally assessed the associations between estimated dietary intake of PCDD/Fs and sperm quality parameters in 200 participants aged 18–40 years from the Led-Fertyl study. Linear regression models, accounting for potential confounding variables, were employed to evaluate the relationships. To estimate the PCDD/Fs exposure, food frequency questionnaires and the latest data on PCDD/Fs concentrations in food, primarily from Spanish sources, were used. Our findings indicate that, in comparison to participants in the lowest tertile, those in the highest tertile (T3) of PCDD/Fs dietary intake exhibited significantly elevated body mass index, increased consumption of meat, fish and eggs, and decreased consumption of nuts. Furthermore, individuals in T3 demonstrated a higher percentage of sperm head abnormalities (4.65 % [0.10; 9.24]; p-trend= 0.037) and a corresponding increase per 1-SD increment in energy-adjusted total PCDD/Fs dietary intake (1.84 % [0.38; 3.68]). No significant associations for other sperm parameters were found. Minimal research exists on PCDD/F dietary exposure and human sperm quality. This study shows significant direct association between higher PCDD/Fs intake and the percentage of sperm head abnormalities which potentially may compromise human reproductive health.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108831"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Humanin alone and in combination with GnRHa therapy attenuates ovarian dysfunction induced by prepubertal cyclophosphamide chemotherapy in female mice","authors":"Liu Liu ,&nbsp;Huawei Wang ,&nbsp;Wen Wen,&nbsp;Shunqing Wang,&nbsp;Liqin Zuo,&nbsp;Yulin Cheng,&nbsp;Meng Rao,&nbsp;Yuru Ma,&nbsp;Li Tang","doi":"10.1016/j.reprotox.2024.108824","DOIUrl":"10.1016/j.reprotox.2024.108824","url":null,"abstract":"<div><div>Prepubertal chemotherapy induced ovarian damage poses a significant threat to female fertility, particularly following cyclophosphamide (CP) treatment. Humanin (HNG), a small molecule polypeptide encoded by mitochondrial DNA, has a variety of effects, this study aimed to investigate the protective effects of HNG and its combination with conventional Gonadotropin Releasing Hormone Agonist (GnRHa) on ovarian function in a CP-induced damage model. The 21-day-old C57BL/6 J female mice were randomly assigned to six groups: Control, CP model, HNG, HNG+CP, GnRHa+CP, and HNG+GnRHa+CP. Reproductive related parameters were assessed through histopathological examination, follicle counts, serum sex hormone levels, estrous cycle monitoring, and oxidative stress evaluation. Results indicated that CP treatment led to significant reproductive dysfunction especially ovarian dysfunction, evidenced by reduced follicles, hormonal imbalances, prolonged estrous cycles, reduced body weight, and diminished ovarian and uterine weights, alongside pathological alterations. Notably, HNG treatment, both alone and in conjunction with GnRHa, significantly mitigated these adverse effects, however the combination did not provide additional benefits over HNG alone regarding follicles preservation and antioxidant capacity. Transcriptomic analysis revealed significant enrichment in inflammation and immune response pathways following HNG treatment. In conclusion, HNG demonstrates potential as a therapeutic agent to protect against CP-induced ovarian damage, offering insights for future strategies aimed at preserving female fertility during chemotherapy.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108824"},"PeriodicalIF":3.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adrenomedullin gene delivery rescues estrogen production in Leydig cells via the inhibition of TGF-β1/Smads signaling pathway","authors":"You-wen Luo ,&nbsp;Xia-lian Zhu ,&nbsp;Zhi-min Yang ,&nbsp;Jian-hua Zhou ,&nbsp;Tong Tao ,&nbsp;Bing-hai Chen ,&nbsp;Song-lin Qin ,&nbsp;Bo-long Liu ,&nbsp;Wei Hu","doi":"10.1016/j.reprotox.2025.108834","DOIUrl":"10.1016/j.reprotox.2025.108834","url":null,"abstract":"<div><div>Our previous findings demonstrated that adrenomedullin (ADM) protects against the reduction in testosterone production and apoptosis of Leydig cells both in vitro and in vivo. In this study, we investigated whether ADM could preserve estrogen production in Leydig cells by suppressing the transforming growth factor-β1 (TGF-β1) / Smads signaling pathway. Leydig cells were treated with lipopolysaccharide (LPS) and recombinant adenovirus ADM (Ad-ADM), an adeno-associated viral vector expressing ADM. Cell viability and cytochrome P450 aromatase (P450arom) activity were assessed. Estrogen, testosterone, and TGF-β1 concentrations in the culture medium were measured. Additionally, the gene expression and protein levels of CYP19, TGF-β1, and Smads were evaluated. The results indicated that Ad-ADM mitigated the reductions in Leydig cell viability and testosterone production, counteracted the decreases in P450arom activity, and restored CYP19 gene expression and protein levels in LPS-treated cells. Moreover, Ad-ADM reduced the elevated gene expression and protein levels of Smads and TGF-β1 induced by LPS. Based on these findings, we propose that ADM safeguards estrogen production in Leydig cells by inhibiting the TGF-β1/Smads signaling pathway.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108834"},"PeriodicalIF":3.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ampligo® 150 ZC affect the expression of sex hormone receptors and cell proliferation marker in female rabbit ovary: Protective effects of thyme essential oil and vitamin C","authors":"Chahrazed Makhlouf ,&nbsp;Hassina Khaldoun ,&nbsp;Louisa Béchohra ,&nbsp;Nacima Djennane ,&nbsp;Amina Settar ,&nbsp;Dalila Tarzaali ,&nbsp;Yasmine Oularbi ,&nbsp;Smail Krabi ,&nbsp;Soumya Bokreta ,&nbsp;Nacira Zerrouki Daoudi","doi":"10.1016/j.reprotox.2025.108833","DOIUrl":"10.1016/j.reprotox.2025.108833","url":null,"abstract":"<div><div>Pesticides tend to cause serious reproductive defects, disturbing endocrine functions and reducing fertility, especially in females. The objective of this work was to identify the reprotoxic effects of Ampligo® 150 ZC (AP), a mixture formulation of lambda cyhalothrin and chlorantraniliprole, on the ovary of female rabbits (<em>Oryctolagus cuniculus</em>) and the possible protective effect of co-treatment with thyme essential oil (TEO), extracted from (<em>Thymus vulgaris</em>) species, and vitamin C (vit C). Twenty female rabbits were divided into four equal groups (n = 5): Control (distilled water), AP (20 mg/ kg bw of the insecticide mixture every other day, by gavage for 28 days), AP+TEO (20 mg/ kg bw of AP + 0.5 mg/ kg bw of TEO every other day), and AP+TEO+Vit C (20 mg/ kg bw of AP + 0.5 mg/ kg bw of TEO + 200 mg/ kg bw of vitamin C every other day). The effects were tested on body weight, ovary histomorphometry, and immunohistochemical expression of AFP, estrogen receptor (ER), and progesterone receptor (PR). The results revealed that AP decreased body and ovarian weights, caused ovarian histological damages, and increased collagen fiber deposition. The immunostaining of the ovary showed a significant (p &lt; .001) increase in AFP and decrease in both ER and PR expressions. In the opposite, co-administration of TEO and vitamin C was effective in improving all caused alterations. In conclusion, combined use of TEO and vitamin C ameliorated the toxic effects of Ampligo® on the ovary in female rabbits.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108833"},"PeriodicalIF":3.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}