Number Of Follicles Research Articles

Improved reproductive outcomes in normogonadotropic oligomenorrheic women undergoing ovarian stimulation with intrauterine insemination: a retrospective cohort analysis of real-world data.

This study aimed to evaluate the comparative reproductive outcomes of ovarian stimulation combined with intrauterine insemination using partner's sperm (OS-IUI) in eumenorrheic and normogonadotropic oligomenorrheic women. A retrospective cohort study was conducted, including 3833 couples who underwent 5920 cycles of OS-IUI between June 2013 and March 2019. Participants were stratified into two cohorts based on menstrual regularity: eumenorrheic and normogonadotropic oligomenorrheic. The primary outcome measured was the live birth rate (LBR) per cycle and cumulative LBR per couple. Secondary outcomes encompassed the clinical pregnancy rate (CPR) per cycle, miscarriage rate, and multiple pregnancy rate. Propensity score matching (PSM) was utilized to balance maternal baseline characteristics. Prior to PSM, significant differences in CPR, LBR and cumulative LBR were observed between eumenorrheic and oligomenorrheic women, favoring the latter (CPR: 11.16% vs. 18.75%; LBR: 9.02% vs. 14.96%; cumulative LBR: 13.60% vs. 24.25%, P < 0.001). These differences persisted post-PSM (CPR: 9.74% vs. 19.29%; LBR: 7.30% vs. 16.29%; cumulative LBR 7.76% vs. 19.90%, P<0.001). Multivariate regression analyses revealed that menstrual status was a significant independent predictor of both CPR (adjusted odds ratio [OR]=1.83 before PSM, 2.24 after PSM) and LBR (adjusted OR=1.90 before PSM, 2.46 after PSM). In the subgroup analysis, female age was identified as the sole predictor of reproductive outcomes in oligomenorrheic women undergoing OS-IUI. Conversely, in eumenorrheic women, factors such as age, duration of infertility, body mass index (BMI), ovarian stimulation agents, and the number of dominant follicles were significant influencers of CPR and LBR. Normogonadotropic oligomenorrheic women demonstrated improved reproductive outcomes with OS-IUI, suggesting that tailored treatment strategies based on menstrual regularity could optimize success rates in infertility management.

Influence of sire plane of nutrition and targeted body weight gain on ewe lamb growth, glucose metabolism, and ovarian reserve.

Rambouillet rams were managed on either a positive (POS; gain 12% body weight [BW]; n = 8), maintenance (MAINT; maintain BW; n = 8), or negative (NEG; lose 12% BW; n = 8) plane of nutrition before breeding. Rams were bred to ewes (n = 10 per ram) that were managed similarly throughout gestation, and lambs were fed a common diet postnatally. Two ewe lambs (7.6 ± 0.02 months of age, BW = 47.1 ± 1.17kg) from each sire were selected and within pair, randomly assigned to be managed for a moderate (MOD, 0.11kg/d; n = 23) or accelerated (ACC, 0.20kg/d; n = 22) rate of gain for 56 d. Ewe lamb BW was recorded on a weekly basis and blood was collected on d 0, 28, and 56 for analysis of insulin-like growth factor 1 (IGF-1), triiodothyronine (T3), thyroxine (T4), glucose, blood urea nitrogen (BUN), and non-esterified fatty acids (NEFA). Intravenous glucose tolerance tests (IVGTT) were conducted from d -7 to -4 and d 57 to 64. A unilateral ovariectomy was performed and ovarian follicles were staged and counted macro and microscopically. Sire treatment × day and ewe treatment × day interactions were present for BW (P ≤ 0.05), where POS had slower growth than MAINT and NEG, and tended (P = 0.10) to have reduced average daily gain (ADG) when managed at an accelerated rate of gain.By design, ACC had greater BW and ADG than MOD (P < 0.05). Concentrations of IGF-1 and T4 were greater in ACC than MOD (P ≤ 0.05), and NEG tended to have greater concentrations of IGF-1 than POS and MAINT (P = 0.08). At the first IVGTT, concentration of insulin was influenced by a sire treatment × time interaction (P ≤ 0.05), suggesting impaired secretion in NEG-sires ewes, but no differences in area under the curve (AUC) for glucose, insulin, or their ratio (P ≥ 0.11). No interactive effects of sire and ewe treatment (P ≥ 0.52) were observed at the second IVGTT, but insulin and insulin:glucose ratio were influenced by sire treatment × time (P ≤ 0.02), as NEG had greater insulin concentration at 60min than MAINT (P = 0.03) and greater AUC than POS and MAINT (P ≤ 0.04). No differences in ovary size, weight, or total counts of macro and microscopic follicles were observed (P ≥ 0.23). Ewes fed ACC had a greater number of small surface follicles (P = 0.02), whereas MOD tended to have a greater number of large surface follicles and tertiary follicles (P < 0.06). These findings suggest that paternal plane of nutrition influences female offspring physiology, particularly at varying growth rates.

Short-Term Metformin Therapy in Clomiphene Citrate Resistant PCOS Patients Improves Fertility Outcome by Regulating Follicular Fluid Redox Balance: A Case-Controlled Study.

To determine the effect of short-term metformin administration on follicular fluid (FF) total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and nuclear factor kappa B (NF-kB) in women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). Fifty-eight patients aged 23-34 who were planned to have intracytoplasmic sperm injection due to clomiphene citrate-resistant PCOS were included in the study. Participants were divided into two groups according to whether they used metformin or not. While 30 of 58 PCOS patients were using short-term metformin in combination with controlled ovarian stimulation, 28 PCOS patients were not using metformin. Metformin was started in the mid-luteal period and continued until the day before oocyte retrieval at 850 mg twice daily. To determine FF-NF-kB, TAS, TOS and OSI values, a dominant follicle ≥17-18 mm in diameter was selected for aspiration. The number of mature follicles and fertilization rates of the metformin group were significantly higher than those not taking metformin. FF-TOS and OSI of the metformin group were significantly lower than those of the group not receiving metformin. Patients receiving metformin had higher FF-TAS than the group not receiving metformin. FF-NF-kB levels of the metformin group were significantly lower than the group not receiving metformin. Insulin resistance, FF-NF-kB and FF-TOS were negatively correlated with the number of mature oocytes. FF-TAS was positively correlated with the number of oocytes. Short-term metformin treatment in clomiphene-resistant PCOS improves the number of mature follicles and fertilization rates by regulating the intra-follicle redox balance.

Comparison of highly purified human menopausal gonadotropin and recombinant follicle stimulating hormone use in patients undergoing in vitro fertilization with progestin-primed ovarian stimulation protocol: a single center retrospective analysis.

Recently, progesterone has been used to prevent LH surge instead of GnRH analogues during ART treatments, which is known as progesterone-primed ovarian stimulation (PPOS) protocol. During ART treatment, highly purified human menopausal gonadotropin (HP-hMG) and recombinant follicle stimulating hormone (rFSH) are two of the agents used for stimulation of antral follicles. The aim of this study is to compare the efficacy and success of HP-hMG and rFSH agents in the ovarian stimulation step of the PPOS protocol, which has not been previously reported in the literature. This retrospective study was conducted at a university hospital with patients who underwent IVF treatment using PPOS protocols in between January 2019 and July 2021. For ovarian stimulation, rFSH was used in group I and HP-hMG was used in group II. Mature oocyte ratio was the primary outcome, and live birth rate was the secondary outcome. Mann-Whitney and Chi-square tests were used for statistical analysis. All p values below 0.05 were considered significant. Total numbers of follicles, oocytes, MII, and 2PN numbers obtained were similar between the two groups. The fertilization rates were 66.7% in the rFSH group and 64.3% in the HP-hMG group (p > 0.05). The pregnancy rates were 53.5% and 46.7% in the rFSH and HP-hMG groups, respectively. There was no statistically significant difference between pregnancy, abortus, and live birth rates. In this study, it is demonstrated that stimulation of oocytes with either rFSH or hMG in the PPOS protocol, which has been added to IVF treatment protocols in recent years, had no statistical difference regarding mature oocyte numbers and live birth rates between the two groups. These results are consistent with the previous literature which compared rFSH and hMG in GnRH agonist and antagonist protocols.

Assessment of ovarian cortex follicles in chemotherapy naïve and chemotherapy exposed patients.

Histological evaluation of ovarian tissue harvested as part of the attempt to preserve fertility might clarify the mechanism by which ovarian failure is caused. The purpose of this study was to compare the histologic appearance of ovarian tissue harvested for ovarian tissue cryopreservation (OTC) in chemotherapy naïve and chemotherapy exposed patients regarding the presence of follicles in different stages of development and to explore ovarian tissue histology in patients exposed to low- and high-cytotoxicity risk chemotherapy. A cohort of post-pubertal cancer survivors who underwent OTC between 1997 and 2018 was evaluated. An expert pathologist reviewed the pathology slides taken during OTC. The assessment included counting number of primordial, primary, secondary, and antral follicles. A comparison was made between chemotherapy naïve and chemotherapy exposed women and further between women who previously received low- versus high-risk gonadotoxic regimens. Seventy post-pubertal patients were included in the study. Seventeen (24.3%) received chemotherapy prior to OTC, and 53 (75.7%) were chemotherapy naïve at the time of OTC. A significant difference was found only in the number of secondary follicles, which was increased in chemotherapy naïve patients (2.81±4.26 vs. 0.88±1.18, respectively; P=0.005). Similar results were observed in a subgroup analysis of hematologic malignancies separately. Comparison of patients with previous exposure to chemotherapy revealed similar follicular appearance, except for the number of secondary follicles, which was higher in patients receiving low-risk compared to high-risk chemotherapy (1.40±1.28 vs. 0.14±0.35, respectively; P=0.006). The ovarian follicular pool at OTC appears comparable between chemotherapy naïve individuals and those post-exposure, as well as among patients receiving low versus high-risk gonadotoxic regimens, with the exception of secondary follicles, which are presented in increased numbers in chemotherapy naïve and those exposed to low-risk gonadotoxic chemotherapy.

Transrectal oocyte retrieval for fertility preservation in virginal women

Research QuestionFertility preservation faces barriers due to sociocultural and religious factors in some countries for nulliparous women who are virgins. Transrectal oocyte retrieval is an alternative technique which can address this by circumventing sensitivities around pelvic procedures in such women who require to have oocyte cryopreservation for medical or social reasons. The study aims to evaluate safety and efficacy of Transrectal oocyte retrieval (TROR) procedure for fertility preservation in these women. DesignA retrospective single centre study of 105 nulliparous women from five satellites of Fakih IVF in the United Arab Emirates, who underwent TROR for oocyte cryopreservation. Extensive bowel preparation and rectal cleansing was performed prior to oocyte retrieval. Outcome and safety data were collected on patient characteristics, stimulation protocols, oocyte yield in relation to age, AMH, number of follicles, and BMI. ResultsThis study evaluated 105 patients who underwent 152 cycles of ovarian stimulation and TROR. The most common indication was social fertility preservation. Correlation with patient characteristics included age, and AMH were performed. AMH showed a statically significant positive correlation with number of oocytes (p≤0.003). No intraoperative or postoperative complications were observed. ConclusionOur study demonstrated that TROR is Our study demonstrated that TROR is an alternative and clinically-effective oocyte harvesting procedure in ART, producing good results in terms of oocyte yield, with no complications and good safety profile. Although Transvaginal oocyte retrieval remains the gold standard treatment, for virginal women where transvaginal oocyte retrieval is not an option, TROR is safe and effective.

Acupuncture Combined with Bushen-Jianpi Decoction Ameliorates the Ovarian Function of Diminished Ovarian Reserve Rats by Regulating Phosphoinositide 3-Kinase/AKT Signaling.

This study aimed to explore the therapeutic efficiency as well as mechanism of acupuncture combined with Bushen-Jianpi decoction (BJD) to treat rats with diminished ovarian reserve (DOR). A DOR rat model was constructed using zona pellucida 3 peptide, and acupuncture, BJD, and their combination were administered as therapeutic interventions. We measured changes in the ovarian indexes, the number of follicles at all levels, the serum levels of sex hormones and immune factors, the expression levels of phosphoinositide 3-kinase (PI3K), AKT, p-AKT, and caspase-3, and the changes in the proportions of splenic T cell subtypes, including T-helper 17 (Th17), Tc17, regulatory T (Treg), CD4+, and CD8+ cells. Acupuncture combined with BJD induced a decrease in the levels of follicle-stimulating and luteinizing hormones, and the effect was greater than that elicited by BJD or acupuncture alone (P < 0.05). Additionally, this combination treatment effectively abrogated the increase in the levels of interleukin-2 (IL-2), IL-17, anti-zona pellucida antibody, and cleaved caspase-3 (P < 0.05), while promoting the regulation of IL-6 and p-AKT (P < 0.01). Furthermore, treatment with acupuncture combined with BJD restored the proportions of CD4+ cells and the CD4+ / CD8+ T cell ratio (P < 0.01), decreased the proportion of CD8+ T and Th17 cells (P < 0.01), and increased the proportions of Tc17 and Treg cells (P < 0.01). Combining acupuncture with BJD can enhance ovarian function in DOR rats. The regulation of sex hormone levels and immune function in rats may be attributed to the adjustment of the mRNA and proteins levels of PI3K, AKT, and caspase-3 in the PI3K/AKT signaling pathway, which leads to an improvement in the immune function of DOR rats.

Melatonin Protects Against Mitochondrial Dyshomeostasis and Ovarian Damage Caused by Chronic Unpredictable Mild Stress Through the eIF2α-AFT4 Signaling Pathway in Mice.

Stress is an emotional state caused by an unexpected external environmental change or stimulus, and several experiments have demonstrated its negative impact on ovarian function, ultimately affecting reproductive ability. Melatonin (MT) has been shown to facilitate oocyte maturation and enhance ovarian function by regulating mitochondrial function. However, the specific effect and underlying molecular mechanisms of MT on stress-induced ovarian dysfunction remain largely unknown. In this study, we established a mouse model of chronic unpredictable mild stress (CUMS) to investigate its impact on ovarian function. Our findings revealed that CUMS led to premature ovarian insufficiency (POI) in mice, characterized by a reduction in follicle numbers and decreased levels of anti-Müllerian hormone (AMH) and bone morphogenetic protein 15 (BMP15). Furthermore, CUMS caused decreased expression of mitochondrial fission protein 1 (FIS1) and enhanced level of mitochondrial fusion protein optic atrophy 1(OPA1), mitofusin1(MFN1), as well as nucleus-encoded protein succinate dehydrogenase complex A (SDHA), reflecting mitochondrial dyshomeostasis. Additionally, CUMS resulted in excessive autophagy and apoptosis. However, MT reversed these effects and improved ovarian damage. Importantly, the protective effects of MT were mediated through the inhibition of the eIF2α-AFT4 pathway. Overall, this study provides valuable insights into the treatment of POI caused by CUMS.

High Carbohydrate, Fat, and Protein Diets Have a Critical Role in Folliculogenesis and Oocyte Development in Rats.

To date, there is no comparative data on the effects of carbohydrates, fat, and proteins, which are macronutrients, on female reproductive functions. Therefore, in this study, we investigated the effects of diets enriched with carbohydrates, fats, and proteins on folliculogenesis and oocyte development in female rats. 21-day-old rats that were just weaned were divided into 4 groups: control, carbohydrate, fat, and protein. The control group was fed with standard chow and the carbohydrate, fat, and protein groups were fed diets enriched with 75% carbohydrate, 60% fat, and 50% protein for 11 weeks, respectively. It was found that high-fat and high-protein diets caused an increase in the estrous cycle length compared to carbohydrate group (p < 0.05). Graafian follicle number decreased in the protein group compared to the control (p < 0.05). However, the atretic follicle number was higher in the fat group compared to the control group (p < 0.05). In the carbohydrate group, Zp1 was found to be lower than the control and protein groups, Zp2 was found to be lower than the control, and Zp3 was found to be lower than the fat group (p < 0.05). While BMP15 was similar between groups (p > 0.05), GDF9 was lower in all diet groups compared to the control (p < 0.05). Foxo3a was lower in the protein group compared to carbohydrate and control (p < 0.05). GAS2 was found to be higher in the control group than the fat group, and higher in the carbohydrate group than the fat and protein groups (p < 0.05). FSH, LH, Progesterone, and E2 levels were higher in all three diet groups than in the control (p < 0.05). Also, significant differences were observed between the groups regarding adiponectin, resistin, and leptin levels. Taken together, high carbohydrate, fat, and protein intake are associated with impairment of the menstrual cycle, depletion of the developing follicle types, and altered expression of folliculogenesis-specific genes and hormones. Therefore, long-term macronutrient diets may result in shortened reproductive periods and reduced fertilization potential in females in the long run.

The effect of norepinephrine on ovarian dysfunction by mediating ferroptosis in mice model.

Studies have shown that stress is associated with ovarian dysfunction. Norepinephrine (NE), a classic stress hormone involved in the stress response, is less recognized for its role in ovarian function. In this study, an NE-treated mouse model is induced by intraperitoneal injection of NE for 4 weeks. Compared with normal control mice, NE-treated mice show disturbances in the estrous cycle, decreased levels of anti-Mullerian hormone (AMH) and estradiol (E2), and increased level of follicle-stimulating hormone (FSH). Additionally, the numbers of primordial follicles, primary follicles, secondary follicles, and antral follicles are decreased, whereas the number of atretic follicles is increased in NE-treated mice, indicating NE-induced ovarian dysfunction. RNA sequencing further reveals that genes associated with ferroptosis are significantly enriched in NE-treated ovarian tissues. Concurrently, the levels of reactive oxygen species (ROS), ferrous ions, and malondialdehyde (MDA) are increased, whereas the expression level of glutathione peroxidase 4 (GPX4) is decreased. To elucidate the mechanism of NE-induced ferroptosis in ovaries and the potential reversal by Coenzyme Q10 (CoQ10), an antioxidant, we conduct both in vitro and in vivo experiments. In vitro, the granulosa cell line KGN, when treated with NE, shows decreased cell viability, reduced expression of GPX4, elevated levels of ferrous ion and ROS, and increased MDA level. However, these NE-induced changes are reversed by the addition of CoQ10. Compared with the NE group, the NE-treated mice supplemented with CoQ10 present increased GPX4 level and decreased iron, ROS, and MDA levels. Moreover, the differential expression of genes associated with ferroptosis induced by NE is ameliorated by CoQ10 in NE-treated mice. Additionally, CoQ10 improves ovarian function, as evidenced by increased ovarian weight, more regular estrous cycles, and an increase in follicles at various stages of growth in NE-treated mice. In conclusion, NE induces ovarian dysfunction by triggering ferroptosis in ovarian tissues, and CoQ10 represents a promising approach for protecting reproductive function by inhibiting ferroptosis.

Expert Opinion on Refined and Extended Key Performance Indicators for Individualized Ovarian Stimulation for ART

ObjectiveTo assess the adequate ovarian follicular development and oocyte recovery between ovarian potential (antral follicle count [AFC]) before the start of ovarian stimulation (OS) and oocyte quantity and quality at oocyte retrieval. A holistic overview of the current key performance indicators (KPIs) was applied to identify the complementary strengths and identify where the current repertoire can be expanded. DesignExpert opinion. SubjectsNot applicable. InterventionNone. Main Outcome MeasuresTo formulate a proposal for a refined and expanded repertoire of KPIs for individualized OS for Assisted Reproductive Technology. ResultsThe performance and outcomes of OS on ovarian follicular development can be evaluated through the application of defined KPIs. Current KPIs for OS are the ovarian sensitivity index (OSI), the follicular output rate (FORT), the oocyte retrieval rate (ORR), and the follicle to oocyte index (FOI). Notably, there are no specific KPIs dedicated to the assessment of follicular development (i.e., recruitment, selection, growth and dominance). In light of this, we recommend expanding the current KPIs for OS to include “Early FORT” (accounting for the number of follicles measuring ≥10–11 mm on Day 5/6 of OS relative to AFC) and “Modified FORT” (the ratio between the number of follicles measuring ≥12 mm at the time of oocyte maturation triggering and AFC); the extension of ORR to include two discrete categories at oocyte retrieval: follicles ≥12 mm and follicles ≥16 mm, to ensure all responsive follicles are accounted for; and FOI to be measured at oocyte maturation triggering and oocyte retrieval ("Advanced FOI”). ConclusionsOnce validated and adopted in clinical practice, we envisage that the proposed expanded KPIs measuring the effect of OS on follicular development (recruitment, selection, growth and dominance) will increase the understanding of the relationship between ovarian reserve measured by AFC and oocyte quantity and quality at oocyte retrieval. This understanding will enable physicians to better evaluate the direct effect of different gonadotropins and doses on ovarian response, leading to a more personalized approach to OS in the context of ART treatment.

Oocyte retrieval of few follicles does not require analgesia – a large-scale multicentre pain analysis

Research questionWhat is the pain intensity of oocyte retrieval (oocyte pick-up, OPU) without anaesthesia and analgesia in women with low or medium number of follicles? DesignMulti-centre observational study analysing IVF cycles without anaesthesia and analgesia was performed in seven IVF centres in Germany and Switzerland between January 2022 and March 2023. In total, 2290 cycles of NC-IVF or minimal stimulation IVF from 1039 patients were recorded. Pain score was assessed using a visual analogue scale (VAS), graded 0 to 10 (0 = no pain; 10 = worst pain possible). A descriptive analysis was performed first, followed by a statistical evaluation using a linear mixed model to analyse the effect of the number of oocytes retrieved and of the number of repeated IVF cycles on the pain score. ResultsThe number of oocytes retrieved varied from 0 to 16 (interquartile range 1-2). Pain score varied from 0 to 10 with a median pain score of 3.0 (interquartile range 2-4), defined as “mild” pain. Compared to a reference value of aspirations with 1 oocyte, the pain score increased slightly by 0.5 points if no oocyte was retrieved, by 0.42 points if 2-5 oocytes were retrieved and by 1.14 points if ≥6 oocytes were retrieved. Pain decreased slightly with repeated aspirations (-0.05 points per cycle) (p=0.028). The complication rate per aspiration was <0.1% requiring hospitalisation. ConclusionPain intensity during OPU of one or few follicles is only mild. In these cases, OPU can be offered without anaesthesia and analgesia to reduce aspiration time and cost.

Network pharmacological analysis and experimental verification of Zisheng Tongmai decoction in the treatment of premature ovarian failure.

Premature ovarian failure (POF) is a disease that seriously jeopardizes women's physical and mental health worldwide. Zisheng Tongmai decoction (ZSTMD), a famous Traditional Chinese Medicine (TCM) formula, has a marked effect on the clinical treatment of POF. This study investigated the potential mechanism of ZSTMD to improve POF through network pharmacology and experimental validation. The active components, key targets and potential mechanisms of ZSTMD against POF were predicted by network pharmacology and molecular docking. The POF model was induced in rats by cyclophosphamide (CTX) and subsequently gavaged with different doses of ZSTMD. KGN cells were treated with different concentrations of quercetin and CTX. Histopathological were observed via hematoxylin and eosin (H&E) staining and immunofluorescence staining. Serum estrogen levels were detected via ELISA. Protein expression was detected via Western blot. We identified quercetin as the main active ingredients targeting VEGFA. Molecular docking showed that VEGFA interacted well with the main active components of ZSTMD. In vivo experiments, ZSTMD significantly increased body weight and the ovarian index, significantly increased E2 and AMH, and decreased FSH and LH in POF rats. Histologic results showed that ZSTMD increased the number of follicles and vascular density in the ovary. It also increased VEGFA and CD31 protein expression. In vitro experiments, quercetin suppressed CTX-induced apoptosis in KGN cells and increased VEGFA protein expression. Our study demonstrated that ZSTMD improves POF by promoting angiogenesis through VEGFA target.

Effects of different rapeseed varieties on egg production performance, egg quality, hormone levels, follicle development, and thyroid function in hens

This study was to evaluate the effects of rapeseed (Brassica napus L.) from China with different content of glucosinolate (Gls) and erucic acid (EA) on laying hens. A total of 600 laying hens at 33 wk of age were randomly divided into 5 treatments containing a control diet and 4 diets with 11.5% rapeseed. The 11.5% rapeseed diets varied in Gls and EA levels: 1) Deyou no. 6 (DY6) with Gls at 22.67 μmol/g and EA at 0.7%, 2) Mianbangyou no. 1 (MB1) with Gls at 43.23 μmol/g and EA at 3.5%, 3) Deyou no. 5 (DY5) with Gls at 74.66 μmol/g and EA at 16.20%, 4) Xiheyou no. 3 (XH3) with Gls at 132.83 μmol/g and EA at 44.60%. Each group had eight replicates and each replicate had 15 hens. The trial lasted for 12 wk with 4 wk withdrawal. From 1 to 8 wk of the trial, 11.5% rapeseed reduced average daily feed intake (ADFI) compared to the control group (P = 0.002), and egg-laying rate of XH3 rapeseed was lower than that of DY6 rapeseed (P = 0.006), and egg weight of MB1, DY5, and XH3 rapeseed were lower than that of the control group (P < 0.01). Egg mass was reduced by 11.5% rapeseed (P = 0.004) and egg mass of XH3 and DY5 rapeseed were lower than that of DY6 rapeseed (P < 0.01). Feed conversion ratio (FCR) of 11.5% rapeseed was higher than that the control group and FCR is higher in XH3 rapeseed than in DY6 rapeseed from 1 to 8 wk (P < 0.01). At wk 8, the lightness value of eggshell color of XH3 rapeseed was significantly lower than that of the control and DY5 rapeseed (P = 0.012). Xiheyou no. 3 rapeseed had a higher redness value of eggshell color than the control and MB1 and DY5 rapeseed (P = 0.008). Albumen height of DY5 rapeseed was lower than that of the control group at wk 8 (P = 0.012). Mianbangyou no. 1 and DY5 rapeseed decreased Haugh unit at wk 4 and 8, respectively (P = 0.011, P = 0.024). Serum E2 content was decreased by 11.5% rapeseed (P = 0.003). Thyroid index increased as the Gls and EA content increased (P = 0.008). The smallest hierarchical follicle numbers of XH3 and MB1 rapeseed were lower than that of the control group (P = 0.009). After 4 wk withdrawal, the egg weight, egg mass, and FCR did not recover (P = 0.011, P = 0.033, P = 0.024, respectively). In conclusion, 11.5% rapeseed decreased egg production performance which might be caused by decreasing hormone levels, and high Gls and EA rapeseed had a lower performance than low Gls and EA rapeseed.

TsRNA-3043a intensifies apoptosis and senescence of ovarian granulosa cells to drive premature ovarian failure by targeting FLT1.

Premature ovarian failure (POF) represents the pathological aging of the ovary. The tRNA-derived small fragments (tsRNAs) play significant roles in diseases; however, whether tsRNAs are involved in POF remains unknown. The cell and mice models of POF were established, and the tsRNAs profile in the ovarian tissues of POF mice was revealed through sequencing. The functions of tsRNA-3043a and its target gene FLT1 in POF cells and mice were detected. POF mice were characterized by a decreased number of normal follicles, ovarian weight, SOD level, and serum contents of E2, LH, and FSH. A total of 81 tsRNAs were aberrantly expressed in the ovarian tissue of POF mice. The expression of tsRNA-3043a was up-regulated in POF mice. tsRNA-3043a mimics inhibited the proliferation and promoted apoptosis, lipid accumulation, and cellular senescence of ovarian granulosa KGN cells, as well as altered the transcriptome. tsRNA-3043a inhibitor had the opposite effect. tsRNA-3043a targets and binds to FLT1. Overexpression of FLT1 protected KGN cells from pathological aging. tsRNA-3043a promotes the progression of POF by inhibiting FLT1 in vitro and in vivo. tsRNA-3043a targets FLT1 and promotes apoptosis and senescence of ovarian granulosa cells, leading to the progression of POF. This study provides a new target for pharmacological intervention in POF.

Nicotinamide mononucleotide supplementation rescues mitochondrial and energy metabolism functions and ameliorates inflammatory states in the ovaries of aging mice.

Noninvasive pharmacological strategies like nicotinamide mononucleotide (NMN) supplementation can effectively address age-related ovarian infertility by maintaining or enhancing oocyte quality and quantity. This study revealed that ovarian nicotinamide adenine dinucleotide levels decline with age, but NMN administration significantly restores these levels, preventing ovarian atrophy and enhancing the quality and quantity of ovulated oocytes. Improvements in serum hormone secretion and antioxidant factors, along with decreased expression of proinflammatory factors, were observed. Additionally, a significant increase in the number of ovarian follicles in aging individuals was noted. Scanning electron microscopy data indicated that NMN significantly alters the density and morphology of lipid droplets and mitochondria in granulosa cells, suggesting potential targets and mechanisms. Transcriptomic analysis and validation experiments collectively suggested that the beneficial effects of NMN on aging ovaries are mediated through enhanced mitochondrial function, improved energy metabolism, and reduced inflammation levels. Our results suggest that NMN supplementation could improve the health status of aging ovaries and enhance ovarian reserve, offering new insights into addressing fertility challenges in older women through assisted reproductive technology.

An Experimental Study of Morphofunctional Features of Hair Follicles Early Response in Cyclophosphamide-Induced Alopecia

The aim of the study was to determine the effect of 3-β-methoxy-Δ18-oleanene (miliacin) on the structural and functional reorganization of hair follicles at the early response stage in the simulated cyclophosphamide-induced alopecia. Material and methods. The study involved 30 male C57BL/6 mice with the anagen stage induced by depilation of hair shafts from the skin of the back. The animals were divided into five groups: I and II – control groups, III, IV and V groups – experimental ones. The animals of group I were exposed to depilation only. The animals of group IV was daily exposed to topical skin applications of 3-β-methoxy-Δ18- oleanene (miliacin) diluted in polyoxyethylated (20) sorbitan oleate in the area of depilation. The animals of group V were only exposed to polyoxyethylated (20) sorbitan oleate. In 9 days after depilation, the animals of the experimental groups received a single injection of cyclophosphamide solution, dosage 125 mg/kg, intraperitoneally; the animals of the control group II received the same volume of 0.9% sodium chloride solution. All animals were withdrawn from the experiment on day 15. The skin of the back in the depilation zone was studied using light microscopy, morphometry and statistics. Results. In 15 days after anagen induction, all hair follicles were synchronized at the anagen VI stage in the skin of mice in the control groups. Exclusively dystrophic forms of hair follicles were detected in the skin of mice of groups III and V. In the skin of animals of group IV, hair follicles predominated in the early and middle anagen stages without signs of dystrophy; the portion of hair follicles in the late dystrophic catagen stage accounted for only 9.2±3.27% of the total number of hair follicles. Conclusion. Topical use of a composition with 3-β-methoxy-Δ18-oleanene (miliacin) leads to an accelerated transition of chemically damaged hair follicles from the anagen VI stage to the dystrophic catagen and a shortening of the telogen stage, which resulted in the entry of the overwhelming majority of hair follicles of mice in this group into the next new cycle of hair follicle development (anagen stages I, II, III).

Ovarian and Uterine Morphology in Minipuberty: Associations with Reproductive Hormones. A COPANA Study of 302 girls.

Female minipuberty is characterized by complex dynamics of circulating reproductive hormones, while the relationship between ovarian and uterine morphology and reproductive hormones remains to be elucidated. To investigate the association between reproductive hormones and ovarian as well as uterine morphology by transabdominal ultrasound (TAUS) at minipuberty. Secondary analysis from The Copenhagen Analgesic Study (COPANA) (ClinicalTrials.gov NCT04369222). Healthy infant girls (n=302, age 3.4 months (0.4) mean (±SD): mamma tissue diameter (mm), n=300. TAUS: uterine volume (n=230), endometrial thickness (n=255), ovarian volume, antral follicle count (total/2-4mm/≥5mm) (n=203).Blood samples (n=269/302=89%): AMH, FSH, LH, inhibin B (immunoassays), progesterone (PROG), androstenedione (Adione), testosterone (T), estrone (E1), estradiol (E2) (LC/MS-MS).Statistics: Pearson/Spearman´s correlation coefficient (parametric/non-parametric data). Total follicle count correlated positively with ovarian volume (r= 0.606, p<0.001), AMH (r=0.378, p<0.001), inhibin B (r=0.251, p<0.001), and negatively with FSH concentrations (r=-0.327, p<0.001). Larger follicles (≥5mm) correlated positively with AMH (r=0.264, p<0.001), inhibin B (0.230, p=0.002), E1 (r=0.209, p=0.004), E2 (r=0.269, p<0.001), PROG (r=0.160, p=0.031) and T (r=0.210, p=0.004) and negatively with FSH (r=-0.183, p=0.015). Circulating E1 and E2 levels correlated with the size of estrogen-responsive tissue sizes: E2 vs. uterine volume (r=0.134, p=0.054), E2 vs. endometrial thickness (r=0.155, p=0.020), E1 and E2 vs. mammary tissue diameter (r=0.213 and r=0.198, respectively, both p < 0.001). Correlations between reproductive hormones and the number of antral follicles suggest that negative feedback in the female HPG axis is established during minipuberty, with ovarian activity promoting uterine and glandular breast tissue growth We provide normative data of infant ovarian- and uterine morphology directly implementable to a clinical setting.

The Effects of L-Tartaric Acid on Ovarian Histostereological and Serum Hormonal Analysis in an Animal Model of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine-related reproductive disorder in women of reproductive age, accompanied by both the impairment of female fecundity and a risk of metabolic disorders. PCOS is emphasized as a worldwide concern due to its unknown etiology and lack of specific medications. The current study aimed to evaluate the effects of L-tartaric acid, an abundantly occurring compound in fruits, on the histostereological and hormonal changes caused by PCOS. Forty adult Sprague Dawley rats were randomly divided into four groups including controls (no intervention), Tartaric acid (40mg/Kg/day from day 21 onwards for 39 days), PCOS (21 days letrozole and then normal saline orally for 39 days), and PCOS + Tartaric acid. After treatments, the ovarian histostereological analysis as well as the level of reproductive hormones including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, progesterone, and testosterone was measured. PCOS caused a significant decrease in the number of unilaminar, multilaminar, antral, and graafian follicles and increased follicular atresia (p-value < 0.001). Moreover, the weight and volume of ovarian tissue and related structures including cortex, medulla, and cysts increased significantly (p-value < 0.0001). However, corpus luteum volume was significantly decreased (p-value < 0.001). Although significant differences were found in some parameters with the control group (p-value < 0.05), the administration of tartaric acid restored the pathological effects of PCOS on the ovarian histostructure. Furthermore, tartaric acid improved the serum levels of LH, estradiol, progesterone, and testosterone (p-value < 0.05). The obtained findings may suggest tartaric acid as a novel strategy for PCOS management, although further studies are necessary.

Effects of Two Types of Estrogen on the Follicular Wave for in Vivo Oocyte Collection in Brown Swiss Cows

The manipulation of follicular waves through hormonal treatments, such as estrogen administration, plays a crucial role in optimizing in-vivo oocyte collection for assisted reproductive technologies. The present study aimed to evaluate the effect of two specific types of estrogen on follicular wave dynamics and their impact on in-vivo oocyte collection in Brown Swiss cows. Fourteen cows, in their first lactation, weighing approximately 340 kg were randomly assigned to one of two treatments including T1 (estradiol cypionate) and T2 (estradiol benzoate). Both treatments were administered at 1.2 mg of estrogen, at day 0 of the experiment. All Brown Swiss cows were provided with a diet entirely consisting of alfalfa grazing. On day 7, follicular wave dynamics were assessed using a DP-50 vet ultrasound device equipped with a 7.5 MHz transducer for transvaginal follicular aspiration guidance. Follicle counts were categorized into three size ranges including 2-4 mm (small), 4-8 mm (medium), and greater than 8 mm (large). Additionally, the quantity and quality (viable oocytes) of the collected oocytes were evaluated by the Ovum Pick Up (OPU) team for oocyte viability on day 7. The study assessed the follicular dynamics (number of follicles) and efficiency of oocyte collection (viable oocytes) in cows treated with Estradiol Cypionate (T1) and Estradiol Benzoate (T2). The average number of small, medium-sized, and large follicles size were 6.048 ± 6.037, 3.16 ± 2.01, and 0.53 ± 0.67 respectively. The total number of follicles was 9.59 ± 3.56. The mean number of viable oocytes recovered was 3.024 ± 1.66, while the mean number of non-viable oocytes was 1.47 ± 1.01. The results indicated no significant differences between treatments in the size of small, medium, and large follicles, nor in the total number of follicles and viable oocytes recovered. However, a significant difference was observed in the number of non-viable oocytes recovered, with a higher mean in T2 (1.86) compared to T1 (1.09). The results indicated an adequate follicular response and viable oocyte recovery in both treatment groups (estradiol cypionate and estradiol benzoate). However, variations in oocyte viability were observed, with estradiol cypionate showing a slight advantage.