Search Results (239)

Objectives: Paratubal cysts (PTCs) are embryological remnants and are potentially hormonally responsive. Since hyperandrogenism (HA) is representative of polycystic ovary syndrome (PCOS), we examined whether biochemical hyperandrogenism is associated with PTCs in women with PCOS and if body mass index (BMI) and insulin resistance (IR) mediate this association. Methods: This retrospective study included 577 women diagnosed with PCOS at a tertiary academic center from 2010 to 2018. Clinical data included age at diagnosis, BMI, and diagnoses of hypertension, non-alcoholic fatty liver disease, and metabolic syndrome. Laboratory measures included total testosterone, sex hormone-binding globulin, anti-Müllerian hormone, luteinizing hormone, fasting glucose, insulin, and triglycerides (TG). Derived indices included a free androgen index (FAI), homeostasis model assessment of insulin resistance (HOMA-IR), and fasting glucose-to-insulin ratio. PTCs were identified through imaging or surgical findings. Structural equation modeling (SEM) assessed direct and indirect relationships between FAI, BMI, HOMA-IR, and PTCs, while adjusting for diagnostic age. Results: PTCs were identified in 2.77% of participants. BMI, FAI, TG, and IR indices were significantly higher for women with PTCs than those without PTCs. SEM revealed significant indirect effects of FAI on PTCs via BMI and HOMA-IR. The direct effect was negative, resulting in a non-significant total effect. A sensitivity model using HOMA-IR as the predictor showed a significant direct effect on PTCs without mediation via FAI. Conclusions: Biochemical HA may influence PTC development in PCOS through metabolic pathways, establishing the need to consider metabolic context when evaluating adnexal cysts in hyperandrogenic women. Full article

Background: Asprosin is a relatively recently discovered glucogenic adipokine secreted during fasting that plays an important role in various biochemical processes in the body, including those connected with obesity and insulin resistance. The aim of this exploratory study was to investigate the associations between selected hormonal, anthropometric, and lifestyle-related parameters and serum asprosin concentration. As studies concerning fertility and asprosin have so far been limited to men or women with PCOS, its role in the general female population remains largely unexplored. The direction of this exploration was thus pointed toward possible connections with female fertility. Methods: The case-control study group included 56 women of reproductive age (25–42 years), who were patients of the Reproductive Health Clinic and the Clinic of Endocrinology, Diabetology, and Internal Medicine of the Medical University of Białystok, Poland. The levels of selected hormones, including anti-Müllerian hormone (AMH), estradiol, sex hormone-binding globulin (SHBG), and testosterone, body composition parameters, and a lifestyle parameter—night fasting duration—were assessed to test their associations with serum asprosin concentration. Results: A weak negative correlation was found between AMH level and serum asprosin concentration, suggesting a potential link between asprosin and ovarian reserve. Furthermore, a moderate positive correlation was found between the percentage of total body water (TBW) and serum asprosin concentration. No significant associations were observed between the levels of the other tested hormones and serum asprosin concentration, or between body composition parameters or night fasting duration and serum asprosin concentration. The multivariate model designed in the study shows that AMH, TBW, and night fasting duration explain 23.4% of asprosin variability. Conclusions: Although the nature of the study is exploratory, the findings indicate that the role of asprosin in the female population—particularly its role in fertility—requires further research. Not only is the number of available studies on asprosin insufficient, but the results of this study partly contradict what is known about the hormone from previous studies, which were largely performed with male cohorts. In addition, the results of this study suggest that asprosin may indeed be involved in mechanisms related to female fertility, particularly those connected with ovarian reserve. Nevertheless, studies performed in larger, more homogeneous populations are necessary to confirm the role of asprosin in women, including its association with female fertility. Full article

The Anti-Müllerian hormone (AMH) is widely recognized for promoting Müllerian duct regression in higher vertebrates and regulating key reproductive functions like steroidogenesis, folliculogenesis, and Leydig cell development. In teleost fish, which lack Müllerian ducts, Amh primarily influences male reproductive functions, including sex determination, testis differentiation, and germ cell proliferation. In adult fish, Amh supports gonad development and spermatogenesis, but its role in teleost gonadal physiology remains largely underexplored. This study reveals a novel steroidogenic function in the European sea bass (Dicentrarchus labrax) using in vitro testis culture, in vivo plasmid injection, and cell-based transactivation assays. The Amh-induced significant increase in androgen levels was also confirmed in Japanese medaka (Oryzias latipes) treated with recombinant sea bass Amh. Beyond activating the canonical Smad pathway, Amh also triggered the cAMP/PKA signalling pathway via its cognate type II receptor, Amhr2. Inhibitors of these pathways independently and synergistically counteracted Amh-induced CRE-Luc activity, indicating pathway crosstalk. Moreover, inhibition of the cAMP pathway suppressed Amh-induced androgen production in testis cultures, emphasizing the crucial role of protein kinase A in mediating Amh steroidogenic action. These findings uncover a novel steroidogenic function of Amh in teleosts and highlight its broader role in male reproductive physiology. Full article

Background: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder characterized by excess body weight, hyperandrogenism, hyperglycemia, and insulin resistance often resulting in hirsutism and infertility. Dietary strategies have been shown to ameliorate metabolic disturbances, hormonal imbalances, and inflammation associated with PCOS. Recent evidence indicates that intermittent fasting (IF) could effectively enhance health outcomes and regulate circadian rhythm; however, its impact on PCOS remain unclear. Objective: Therefore, this systematic review and meta-analysis aims to examine the effect of IF on women diagnosed with PCOS. Methods: Comprehensive research was conducted across three major databases including PubMed, Scopus, and Web of Science without date restrictions. Meta-analysis was performed using Cochrane Review Manager Version 5.4 software. Results: Five studies fulfilled the inclusion criteria. IF significantly reduced body weight (MD = −4.25 kg, 95% CI: −7.71, −0.79; p = 0.02), BMI (MD = −2.05 kg/m², 95% CI: −3.26, −0.85; p = 0.0008), fasting blood glucose (FBG; MD = −2.86 mg/dL, 95% CI: −4.83, −0.89; p = 0.004), fasting blood insulin (FBI; MD = −3.17 μU/mL, 95% CI: −5.18, −1.16; p = 0.002), insulin resistance (HOMA-IR; MD = −0.94, 95% CI: −1.39, −0.50; p < 0.0001), triglycerides (TG; MD = −40.71 mg/dL, 95% CI: −61.53, −19.90; p = 0.0001), dehydroepiandrosterone sulfate (DHEA-S; MD = −33.21 μg/dL, 95% CI: −57.29, −9.13; p = 0.007), free androgen index (FAI; MD = −1.61%, 95% CI: −2.76, −0.45; p = 0.006), and C-reactive protein (CRP; MD = −2.00 mg/L, 95% CI: −3.15, −0.85; p = 0.006), while increasing sex hormone-binding globulin (SHBG; SMD = 0.50, 95% CI: 0.22, 0.77; p = 0.004). No significant changes were observed in waist-to-hip ratio (WHR), total cholesterol (TC), LDL, HDL, total testosterone (TT), or anti-Mullerian hormone (AMH). Conclusions: IF represents a promising strategy for improving weight and metabolic, hormonal, and inflammatory profiles in women with PCOS. However, the existing evidence remains preliminary, necessitating further robust studies to substantiate these findings. Full article

Polygoni Multiflori Radix Praeparata (PMRP), a processed root of Polygonum multiflorum Thunb. (known as Zhiheshouwu in Chinese medicine), exhibits anti-aging properties and is used to improve ovarian aging. However, its therapeutic mechanism against premature ovarian insufficiency (POI) remains unclear. This study investigates whether PMRP alleviates POI by inhibiting PANoptosis—a cell death pathway characterized by the concurrent occurrence and interplay of pyroptosis, apoptosis, and necroptosis. POI was induced in rats using tripterygium glycosides. We evaluated the estrous cycle, serum hormone levels (follicle-stimulating hormone [FSH], estrogen [E₂], anti-Müllerian hormone [AMH]), follicular development, and the ultrastructure of granulosa cells. PANoptosome assembly (apoptosis-associated speck-like protein containing a CARD [ASC]/caspase-8/receptor-interacting protein kinase 3 [RIPK3] co-localization) and key effectors of PANoptosis (caspase 3, cleaved caspase 3, gasdermin D [GSDMD], cleaved GSDMD, GSDME, RIPK1, mixed-lineage kinase domain-like protein [MLKL], and p-MLKL) were analyzed. PMRP restored the estrous cycle, lowered FSH levels, and increased E₂ and AMH levels in POI rats. It reduced follicular atresia, preserved primordial follicles, and suppressed PANoptosis-like death in granulosa cells. Mechanistically, PMRP disrupted PANoptosome assembly and downregulated key effectors of PANoptosis. PMRP alleviates POI by inhibiting PANoptosis in granulosa cells, overcoming the previous limitations of targeting single death pathways and providing novel insights into the pathogenesis and treatment strategies for POI. Full article

Per- and polyfluoroalkyl substances (PFASs) comprise a diverse array of synthetic chemicals that resist environmental degradation. They are increasingly recognised as endocrine-disrupting compounds (EDCs). These chemicals, found in non-stick cookware, food packaging, and industrial waste, accumulate in human tissues and fluids, raising substantial concerns regarding their impact on female reproductive health. Epidemiological studies have demonstrated associations between PFAS exposure and reduced fertility; nevertheless, the underlying molecular pathways remain inadequately understood. This narrative review investigates the multifaceted effects of PFASs on ovarian physiology, including its disruption of the hypothalamic–pituitary–ovarian (HPO) axis, alteration of anti-Müllerian hormone (AMH) levels, folliculogenesis, and gonadotropin receptor signalling. Significant attention is directed towards the emerging association between PFASs and polycystic ovarian syndrome (PCOS), wherein PFAS-induced hormonal disruption may exacerbate metabolic issues and elevated androgen levels. Furthermore, we analyse the current data regarding PFAS exposure in women undergoing treatment based on assisted reproductive technologies (ARTs), specifically in vitro fertilisation (IVF), highlighting possible associations with diminished oocyte quality, suboptimal embryo development, and implantation failure. We examine potential epigenetic and transgenerational alterations that may influence women’s reproductive capabilities over time. This study underscores the urgent need for further research and regulatory actions to tackle PFAS-related reproductive toxicity, particularly in vulnerable populations, such as women of reproductive age and those receiving fertility treatments. Full article

Background: Hashimoto’s thyroiditis (HT), the most prevalent autoimmune thyroid disorder in reproductive-age women, has been linked to diminished ovarian reserve and subfertility. This study aimed to evaluate the relationship between HT and key fertility parameters, including hormonal markers and reproductive outcomes, while also exploring the potential impact of thyroid hormone replacement therapy. Methods: A retrospective observational study was conducted on 86 women undergoing fertility evaluation. Participants were divided into two groups based on anti-thyroid peroxidase antibodies (ATPO): the HT group (n = 49) and the control group (n = 37). Among women with HT, 57% were receiving levothyroxine (Euthyrox^®) at the time of assessment. Variables analyzed included serum levels of anti-Müllerian hormone (AMH), thyroid-stimulating hormone (TSH), insulin resistance index (HOMA-IR), number of oocytes retrieved, blastocysts formed, pregnancies achieved, and live births. Statistical methods included t-tests, Mann–Whitney U tests, Pearson/Spearman correlations, and linear regression models. Results: Women in the HT group had slightly lower AMH levels and oocyte counts compared to controls, though these differences did not reach statistical significance. TSH values were higher in the HT group and showed a significant negative correlation with blastocyst formation (p = 0.03). Although TSH also showed negative trends with oocyte count, pregnancies, and live births, these correlations did not reach statistical significance. A post-hoc subgroup analysis revealed that HT patients receiving levothyroxine tended to have higher numbers of oocytes retrieved and blastocysts formed compared to untreated HT patients, suggesting a possible beneficial effect of thyroid hormone replacement, although the differences were not statistically significant. Conclusions: HT is associated with subtle but clinically relevant impairments in ovarian reserve and reproductive potential. Thyroid hormone replacement may offer modest benefits and should be considered in the individualized management of fertility in women with thyroid autoimmunity. Full article

The anti-Müllerian hormone (amh) and its receptor, amhr2, along with the downstream bone morphogenetic protein receptors (bmprs), have been recognized as the central regulators in teleost sex determination (SD) and differentiation. However, their evolution and function in reproduction among diverse teleost lineages may represent species-specific patterns and still need more explanation. In this study, systematic investigations of amh signaling genes, including amh, amhy (Y-linked paralog of amh), amhr2, bmpr1, and bmpr2, were conducted among teleost species. The results revealed generally conserved gene copy number, phylogeny, structure, and synteny, among teleost amh signaling genes. Notably, significantly accelerated evolutionary rates (dN/dS) were found in teleost amhy compared to amh, and amh exhibited faster molecular evolution in amhy-SD teleosts than in non-amhy-SD teleosts, suggesting their enhanced evolutionary plasticity in teleosts. Expression profiling identified testis-biased expression of the most amh signaling genes in fish species with different SD genes and mechanisms, including Lateolabrax maculatus and Dicentrarchus labrax from Order Perciformes, Cynoglossus semilaevis and Paralichthys olivaceus from Order Pleuronectiformes, and Salmo salar and Oncorhynchus mykiss from Order Salmoniformes, with ovary-biased expression also found in Salmoniformes. A weighted gene co-expression network analysis further uncovered strong species-specific functional interactions between amh signaling components and genes of germ-cell development, the meiotic process, etc. Collectively, the integrated evidence from this study supports the hypothesis that amh signaling provides the key molecules governing sex differentiation in a species-specific manner in diverse teleost lineages, independent of its SD role, and interacts with functions of both testis and ovary development. Full article

Background/Objectives: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autoimmune disorder caused by mutations in the AIRE gene. Approximately 60% of affected females develop premature ovarian insufficiency (POI) by age 30, often most commonly due to steroidogenic autoantibodies. Although APECED is typically diagnosed in childhood, its reproductive implications are underrecognized. This study reports a case of successful fertility preservation in an adult woman with APECED and reviews the relevant literature. Methods: We describe the clinical course of a 37-year-old woman with genetically confirmed APECED who underwent ovarian stimulation for fertility preservation. A comprehensive PubMed search was also conducted to identify English-language case reports on fertility preservation in APECED-associated POI. Results: The patient experienced menarche at age 13, adrenal insufficiency at 14, and menstrual irregularities from age 18. Genetic analysis confirmed an AIRE mutation (NM_000383: exon 11: c.1400+1G>A). Given her relatively high anti-Müllerian hormone level, she opted for fertility preservation and underwent six cycles of ovarian stimulation, resulting in the cryopreservation of 17 mature oocytes. During ovarian stimulation, multiple follicular developments were observed, but serum E2 levels remained low. The literature review identified fewer than 20 reported cases addressing fertility preservation in APECED, highlighting its rarity and the lack of standardized management. Conclusions: Although APECED frequently leads to early POI due to impaired steroidogenesis, residual ovarian function may persist. Early assessment of ovarian reserve and timely fertility counseling are crucial, even in asymptomatic patients or those diagnosed in childhood. Reproductive planning should be integrated into the long-term care of women with APECED. Full article

Background/Objectives: The anti-Müllerian hormone (AMH) is a key biomarker of the ovarian reserve, correlating with ovarian follicle count, fertility outcomes, and menopause timing. Understanding its genetic determinants has broad implications for female reproductive health. However, prior genome-wide association studies (GWASs) have focused exclusively on women of European ancestry, limiting insights into diverse populations. Methods: We conducted a GWAS to identify genetic loci associated with circulating AMH levels in a sample of 1185 Samoan women from two independently recruited samples. Using a Cox mixed-effects model we accounted for AMH levels below detectable limits and meta-analysed the summary statistics using a fixed-effect model. To prioritize variants and genes, we used FUMA and performed colocalization and transcriptome-wide association analysis (TWAS). We also assessed whether any previously reported loci were replicated in our GWAS. Results: We identified eleven genome-wide suggestive loci, with the strongest signal at ARID3A (19-946163-G-C; p = 2.32 × 10⁻⁷) and replicated rs10093345 near EIF4EBP1. The gene-based testing revealed ARID3A and R3HDM4 as significant genes. Integrating GWAS results with expression quantitative trait loci via TWAS, we detected seven transcriptome-wide significant genes. The lead variant in ARID3A is in high linkage disequilibrium (r² = 0.79) with the known age-at-menopause variant 19-950694-G-A. Nearby KISS1R is a biologically plausible candidate gene that encodes the kisspeptin receptor, a regulator of ovarian follicle development linked to AMH levels. Conclusions: This study expands our understandings of AMH genetics by focusing on Samoan women. While these findings may be particularly relevant to Pacific Islanders, they hold broader implications for reproductive phenotypes such as the ovarian reserve, menopause timing, and polycystic ovary syndrome. Full article

Glyphosate and glyphosate-based herbicides (GBHS) are the most widely used herbicides worldwide, yet their potential endocrine-disrupting effects in humans remain inadequately studied. We analyzed data from 1532 participants aged ≥6 years in the 2017–2018 National Health and Nutrition Examination Survey (NHANES). Serum sex hormones assessed included follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), androstenedione, estrone, estradiol, estrone sulfate, 17α-hydroxyprogesterone, progesterone, and sex hormone-binding globulin (SHBG). We found that higher urinary glyphosate levels were significantly associated with lower concentrations of AMH (β = −0.140, p < 0.05), androstenedione (β = −0.134, p < 0.001), estradiol (β = −0.185, p < 0.05), estrone (β = −0.132, p < 0.05), estrone sulfate (β = −0.196, p < 0.001), 17α-hydroxyprogesterone (β = −0.097, p < 0.05), and progesterone (β = −0.212, p < 0.05). SHBG was positively associated (β = 0.080, p < 0.05). FSH and LH showed no significant associations. These associations were generally linear and showed modification by age. Subgroup analyses revealed stronger negative associations in adult males, while SHBG increased in females. In conclusion, we observed that higher urinary glyphosate levels were significantly associated with alterations in multiple serum sex hormones. Although the cross-sectional design precludes causal inference, these findings underscore the need for longitudinal research to determine temporal relationships and underlying mechanisms. Full article

Background/Objectives: As the population of women with endometriosis increases, approximately 10% of those of reproductive age experience symptoms such as pelvic pain, painful menstruation, and infertility. Individuals with endometriosis usually undergo multiple surgeries due to the high recurrence rate of the condition. However, ovarian surgery tends to reduce the ovarian reserve, presenting a dilemma when deciding whether to recommend surgery or medical treatment for women of reproductive age. The impact of endometriomas on the residual volume of ovarian tissue remains controversial, and it is unclear whether endometriosis itself or endometriomas are the primary problem. In this study, we aimed to investigate whether women with endometriosis have lower levels of anti-Müllerian hormone than women with healthy ovaries before treatment initiation. Methods: A total of 298 participants enrolled in the endometriosis cohort at Severance Hospital, Korea, from 1 October 2020 to 1 July 2024 were included in this study. Of these, 63 participants were from a retrospective study, and 235 were from a prospective study. Due to the use of different assay methods between the reference values and anti-Müllerian hormone measurements from Severance Hospital, a correction was applied using the regression equation. The mean anti-Müllerian hormone levels for individuals with endometriosis were corrected with the regression equation and compared to those of the reference group for each age group using a one-sample t-test. Results: Anti-Müllerian hormone levels decreased with age in the endometriosis group. When comparing mean anti-Müllerian hormone concentrations between the endometriosis group and reference values, among 168 participants aged 20–31 years, the corrected mean anti-Müllerian hormone concentration was 5.96 ± 3.22 ng/mL, higher than the reference value of 4.94 ± 0.17 ng/mL (p < 0.01). Among 31 participants aged 35–37 years, the corrected average anti-Müllerian hormone value was 4.33 ± 3.06 ng/mL, compared to the reference anti-Müllerian hormone level of 3.22 ± 0.15 ng/mL (p = 0.05). There were no significant differences in corrected anti-Müllerian hormone levels between the 32–34-, 38–40-, 41–43-, and ≥44 years age groups. Conclusions: Patients with endometriosis, especially those aged 20–31 years, tended to have higher anti-Müllerian hormone levels than did individuals with healthy ovaries. In other age groups, there were no differences. Given that these levels do not differ significantly across age groups, it is difficult to conclude that patients with endometriosis have a reduced ovarian reserve. Full article

Background: Wolfram syndrome (WFS), also known as DIDMOAD, is a rare monogenic neurodegenerative disorder characterized by four key components: non-autoimmune insulin-dependent diabetes mellitus (DM), optic atrophy, sensorineural hearing loss, and diabetes insipidus. Although it significantly affects quality of life, gonadal dysfunction, particularly hypogonadism, remains underrecognized. Methods: In total, 45 patients (25 men, 20 women) with genetically confirmed WFS from a single tertiary-care center were prospectively followed to assess gonadal function. Men underwent hormonal evaluations, semen analysis, imaging tests, and testicular biopsies. In women, data on age at menarche, menstrual irregularities, and age at menopause were recorded. Hormonal analyses, including anti-Müllerian hormone (AMH) levels, and imaging tests were also conducted. Results: Hypogonadism was identified in 19 men (76.0%), of whom 17 (68.0%) had hypergonadotropic hypogonadism and 2 (8.0%) had hypogonadotropic hypogonadism. Testicular biopsies showed seminiferous tubule damage, Sertoli cell predominance, and reduced Leydig cells. Azoospermia was observed in 12 patients, whereas others presented with oligozoospermia, teratozoospermia, or asthenozoospermia. Most patients exhibited low testosterone levels along with elevated LH and FSH, suggesting primary testicular failure, except for two cases of hypogonadotropic hypogonadism. Correlations between biomarkers, onset age and severity have been analyzed and provide important insights regarding medical treatment. In women, menstrual irregularities were universal, with 20% experiencing premature menopause. Four patients had low AMH levels, with ovarian atrophy in three and a postmenopausal uterus in two, indicating early hypogonadism risk. Conclusions: Gonadal dysfunction is a significant yet overlooked feature of WFS, requiring systematic evaluation during puberty and beyond. Proper management is essential to mitigate metabolic disturbances and psychological impacts, including infertility distress, relationship challenges, and quality of life concerns. Addressing sexual health is crucial as WFS patients live longer and aspire to establish relationships or start families. Full article

Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor, is released pre-prandially and during periods of negative energy balance, exhibiting anti-fertility properties. In this study, twenty ewes were divided into two groups: a ghrelin-treated group receiving 1.25 μg/kg body weight (BW) of ghrelin per day via mini-pumps for 28 days and an untreated control group. Estrus was synchronized, superovulation was induced with FSH, and embryos and follicular fluid were collected six days post-estrus. Blood samples were taken to measure LH, progesterone, and anti-Müllerian hormone (AMH) concentrations. Results indicated that in treated animals, preovulatory LH surge was weaker, and progesterone levels were lower than in controls. Differences were observed in the superovulatory response and the number of collected embryos, both being higher in controls. While AMH levels did not differ between groups at the beginning of the experiment, they were lower in treated animals at the time of FSH administration. Treated ewes exhibited a reduced number of small follicles, and their follicular fluid contained lower AMH concentrations than the controls. These findings suggest that ghrelin plays a direct role in regulating LH secretion from the pituitary and in controlling ovarian follicle development, highlighting the strong interaction between nutrition and fertility. Full article

Cytokine and Anti-Müllerian Hormone (AMH) profiling were performed in prepubertal Murrah buffalo heifers’ post-progesterone supplementation and Co-synchronization (Co-synch) protocol. Cytokine (IFNγ, IL6, IL1, IL13, TNFα, and TGFβ), AMH, progesterone, and estrogen hormone estimations were conducted. The ovarian follicular pattern and fertility outcome were recorded. Eighteen prepubertal heifers, 15–17 months of age, 250–300 kg body weight (BWt) were randomly divided into three groups, Group 1: n = 6, supplemented with altrenogest 0.044 mg/kg BWt/day/heifer orally for 14 days along with Co-synch program; Group 2: n = 6, implanted Controlled Internal Drug Release (CIDR) for 14 days and co-synch program, Group 3: n = 6, received Co-synch program. Ultrasonography was performed to determine ovarian follicle status on respective days of sampling. Pregnancy diagnosis was performed around 45 and 60 days post artificial insemination (AI). The Estradiol 17-β level remained constant in Group 1, Group 2, and Group 3 during the progesterone treatment and Co-synch treatment. Estradiol levels during Co-synch were significantly less (p = 0.024) on day 9 of Co-synch (14.41 ± 1.97 pg/mL) than on day 0 (20.11 ± 0.36 pg/mL) and on day 7 (19.77 ± 0.34 pg/mL) in prepubertal buffalo heifers in Group 1. However, no significance was observed in other groups. Progesterone levels in buffalo heifers subjected to synchronization protocols varied significantly (p < 0.05) on day 7 of progesterone (P4) treatment between Group 1, Group 2, and Group 3. Supplementation of altrenogest showed a significant (p = 0.043) increase in progesterone levels by day 14 of altrenogest treatment. Progesterone varied significantly in all groups on day 9 of Co-synch protocol [Group 1 (p = 0.020), Group 2 (p = 0.041), and Group 3 (p = 0.007)]. Cytokine IFNγ showed high correlation with progesterone, indicating the role of IFNγ in puberty in buffalo heifers (r = 0.626, p < 0.01). Anti-Müllerian Hormone had a significant positive correlation when supplemented with altrenogest with IFNγ (r = 0.673, p < 0.01) and TGFβ (r = 0.463, p < 0.01), whereas it was a negatively correlated with TNFα (r = −0.34, p < 0.05). Based on Karl Pearson correlation coefficients, IL13 and TGFβ could be considered as markers for puberty in buffalo heifers. Full article