Biomedical subjects

Terhi Piltonen

Publications and source records attributed to Terhi Piltonen.

5 recordsLinked to original sources

PubMed2026

From Gene Function to Precision Intervention: CRISPR/Cas9 and Stem Cell-Based Strategies as Emerging Disease-Modifying Approaches in PMOS.

Polyendocrine metabolic ovarian syndrome (PMOS) is a complex endocrine-metabolic disorder affecting up to 18% of women worldwide and remains the leading cause of anovulatory infertility. Despite extensive research, current treatments primarily target symptoms, including menstrual irregularities, hyperandrogenism, and metabolic dysfunction, without addressing the underlying molecular and tissue-level disturbances. Advances in multi‑omic profiling have identified disruptions across neuroendocrine, metabolic, inflammatory, and extracellular matrix pathways, alongside genetic susceptibility at loci such as DENND1A, CYP17A1, LHCGR, FSHR, IRS1, and PPARG. However, the functional roles of many variants remain unresolved. CRISPR/Cas9 gene editing enables precise interrogation of these pathways, while stem cell-based platforms, including mesenchymal stem cells (MSCs), exosomes, and gene-edited induced pluripotent stem cells (iPSCs), may serve as complementary platforms for regeneration and disease modeling. Preclinical studies demonstrate that MSCs and their derivatives modulate inflammation, restore ovarian structure, and improve metabolic parameters, while iPSC-based models enable patient-specific investigation of steroidogenic and metabolic abnormalities. Translational challenges remain, including targeted delivery, off-target effects, phenotypic heterogeneity, and regulatory considerations. Integrating CRISPR‑based functional genomics with stem cell research may shift PMOS management from symptom‑focused care to targeted, mechanism‑driven interventions that could modify the course of PMOS (Graphical Abstract).

Humans↗

PubMed2026

Genomic analyses implicate hormonal and metabolic dysregulation in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) and its underlying features remain poorly understood. In this genetic study (n = 544,513), we expand the number of genetic loci from 16 to 29, and additionally identify 31 associated plasma proteins. Many risk-increasing loci were associated with later age at menopause, underscoring the reproductive longevity related to an increased oocyte number and/or availability across the lifespan. Hormonal regulation in the etiology of this condition, through metabolic and reproductive features, was emphasized. The proteomic analysis highlighted metabolic biology known to be related to PCOS. A polygenic risk score (PRS) was associated with adverse cardiometabolic outcomes, with differing relevance of testosterone and body mass index in women and men. Finally, while oligo-anovulation and anovulatory infertility are features of PCOS, we observed no impact of PCOS susceptibility on childlessness. We suggest that PCOS susceptibility confers balanced pleiotropic influences on fertility in women, and life-long adverse metabolic consequences in both sexes.

Humans↗

PubMed2005

Serum anti-Müllerian hormone levels remain high until late reproductive age and decrease during metformin therapy in women with polycystic ovary syndrome.

BACKGROUND: Anti-Müllerian hormone (AMH) is secreted by granulosa cells of ovarian early developing follicles and its serum levels have been shown to correlate with small antral follicle number. Since the pronounced androgen secretion from follicles/stroma in women with polycystic ovary syndrome (PCOS) remains until late reproductive age, and since AMH reflects the number of antral follicles, it was of interest to study the possible age-related relationship between AMH, androgens and follicle number in women with PCOS and in control women. Moreover, the possible effect of metformin on serum AMH levels and the relationship to follicle count and volume were studied. METHODS: Forty-four healthy women (aged 21-44 years) and 65 women with previously diagnosed PCOS (aged 16-44 years) participated in the study. Serum basal AMH levels were correlated with those of serum androstenedione, testosterone, estradiol (E2), LH, FSH and inhibin B, and with follicle number. The effect of metformin on serum AMH concentrations, follicle number and ovarian volume was studied in 26 women (aged 20-41 years) with PCOS after 6 months of treatment. RESULTS: Serum AMH levels were 2- to 3- fold higher in PCOS women than in healthy women. In control women, serum AMH levels correlated positively with those of serum androstenedione (r = 0.564, P < 0.001) and testosterone (r = 0.328, P = 0.036) and negatively with serum FSH concentrations (r = -0.374, P = 0.012) and age (r = -0.691, P<0.001). In women with PCOS, serum AMH levels correlated positively with those of androstenedione (r = 0.311, P = 0.011) and testosterone (r = 0.310, P = 0.011) and with follicle count (r = 0.352, P = 0.012), and negatively with age (r = -0.300, P = 0.014). Serum AMH levels, the number of antral follicles and ovarian volume decreased significantly during metfromin treatment. CONCLUSIONS: Serum AMH levels decreased with age both in healthy women and in women with PCOS, although they were always 2- to 3-fold higher and remained elevated until 40 years of age in PCOS subjects. Thus, since serum AMH levels correlate well with antral follicle count and serum androgen levels, the measurement of AMH could be used as a tool to assess ovarian ageing, to diagnose polycystic ovaries/PCOS and to evaluate treatment efficacy.

Adult↗

PubMed2004

Ovarian age-related responsiveness to human chorionic gonadotropin in women with polycystic ovary syndrome.

Ovarian steroid secretion capacity starts to decline as early as around the age of 30 yr. Whether an age-related decrease in androgen secretion, as in normal women, also occurs in women with polycystic ovary syndrome (PCOS) and whether the enhanced androgen production in PCOS remains throughout the fertile period of life are not known. The aim of this study was to determine the age-related serum basal and gonadotropin-stimulated androgen levels in women with PCOS and to compare the results with those obtained from our previous study in healthy women with normal ovaries. Human chorionic gonadotropin (hCG) stimulation tests were carried out among 42 women with PCOS (age, 16-44 yr; body mass index, 31.02 +/- 1.1 kg/m(2)). An im injection of 5000 IU hCG was given 2-4 d after spontaneous or progestin-induced menstrual bleeding, and blood samples for LH, FSH, inhibin B, 17-hydroxyprogesterone, androstenedione (A), testosterone (T), and estradiol assays were collected at 0, 24, 48, and 96 h. In women with PCOS, basal serum T and A levels were about 50% higher than in healthy women. The responses of A and T to hCG [area under the curve (AUC), 96 h)] were significantly higher in women with PCOS than in normal women [A, 1183.6 +/- 60 (+/-se) vs. 814.4 +/- 39 (P <or= 0.001); T, 192.9 +/- 12 vs. 117.4 +/- 6; P <or= 0.001]. In PCOS women, the hCG-stimulated A levels correlated negatively with age (AUC of A: r = -0.044; P = 0.004), and a similar trend was also observed in AUC T levels (AUC of T: r = -0.125, P = 0.425). Despite the higher androgen secretion capacity in PCOS, the basal and hCG-stimulated serum estradiol levels were similar to those observed in normal women. LH correlated positively with age, but basal FSH and inhibin B levels remained unchanged. In conclusion, in PCOS basal serum levels of androgens and ovarian androgen secretion capacity are markedly increased and remain high throughout the reproductive years, although the decreasing ovarian capacity to release androgens in response to hCG stimulation seen in healthy women also occurs in PCOS.

Adolescent↗

PubMed2003

Ovarian age-related responsiveness to human chorionic gonadotropin.

Human fertility starts to decline after the age of 30 yr, but the change in ovarian endocrine function, i.e. estrogen biosynthesis, with advancing age is not well understood. To study age-related changes in androgen secretion and ovarian capacity to synthesize/release androgens in response to human chorionic gonadotropin (hCG) stimulation, 44 healthy women (aged 20-44 yr) were investigated. Just before a single im injection of 5000 IU hCG, blood samples for LH, FSH, inhibin B, 17-hydroxyprogesterone (17-OHP), androstenedione (A), testosterone (T), and estradiol (E(2)) assays were collected. Further samples were taken at 24, 48, 72, and 96 h. The responses of 17-OHP, A, and T to hCG, i.e. areas under the curves (AUC; 96 h), correlated negatively with age (17-OHP: r = -0.427; P = 0.004; A: r = -0.266; P = 0.081; T: r = -0.354; P = 0.018). Despite a decreasing capacity of the ovaries to secrete these estrogen precursors, the basal serum levels of E(2) remained unchanged. This may be due to the rise in serum FSH levels observed as early as after the age of 25 yr [</=25 yr: FSH, 5.1 +/- 0.5 (+/-SE) U/liter; >25 yr: FSH, 7.7 +/- 0.9 U/liter; P = 0.01]. No correlation was found between age and serum inhibin B levels. In conclusion, ovarian androgen secretion capacity starts to decline as early as before the age of 30 yr. Despite that, circulating E(2) levels remain normal for years, possibly due to compensatory mechanisms, reflected by the gradual rise in serum FSH levels.

17-alpha-Hydroxyprogesterone↗