Estrogens, Conjugated Synthetic B(Teva Pharmaceutical Industries Ltd.)

Growth Differentiation Factor 15 (GDF15) increases substantially during pregnancy and is primarily produced by the placenta. Elevated levels of GDF15 have been associated with mental health problems in non-perinatal populations, higher corticosterone levels, and decreased estrogen receptor activity. However, the role of GDF15 in mental health during the perinatal transition remains unknown. This longitudinal study is the first to evaluate pregnancy levels of GDF15 in cerebrospinal fluid (cGDF15), plasma (pGDF15) and placenta GDF15 mRNA, along with mapping plasma GDF15 (pGDF15) level changes from late pregnancy to early postpartum. Moreover, we aimed to evaluate the association between pregnancy cGDF15 levels and cortisol early postpartum, evaluate the association between pregnancy cGDF15 levels and mental health in pregnancy and postpartum, and evaluate the association between pGDF15 and estrogens and high-sensitivity C-reactive protein (CRP).

We included data from 95 women scheduled for a planned cesarean section and obtained cerebrospinal fluid (CSF) and plasma levels of GDF15. We quantified GDF15 mRNA levels in placenta biopsies. Estrogens, high-sensitivity CRP, and mental health measures were further collected on the day or one day before the cesarean section. At five weeks postpartum, mental health measures and saliva samples for cortisol analyses were collected. Correlation analyses for GDF15 in CSF, plasma, and placenta mRNA were performed, along with association analyses for pregnancy cGDF15, Cortisol Awakening Response, and mental health outcomes.

We demonstrated a strong correlation between cGDF15 and pGDF15 (r=0.52; p<0.001) and found that both cGDF15 and pGDF15 correlated with placenta GDF15 mRNA*placental weight (r=0.62, p<0.001 and r=0.44, p=0.008, respectively). During late pregnancy, both estradiol (E2) and estriol (E3) were significantly associated with pGDF15 levels (E2: p=0.002; E3: p(corrected)<0.001). Finally, we found that cGDF15 levels were not associated with self-reported mental well-being or the Cortisol Awakening Response or absolute cortisol at awakening postpartum.

This novel study points to the unique hormonal landscape during the perinatal transition and the specific role of GDF15 in pregnancy, which appears uncoupled with perinatal mental health and cortisol outcomes. Our data also strongly imply that the overall amount of circulating GDF15 in late pregnancy is closely related to placenta size.

In aquatic ecosystems, endocrine-disrupting compounds (EDCs) pose a growing concern for their potential adverse effects on fish reproduction and development. In lake Pyhäjärvi, located in the urban boreal region of Tampere, Finland, a significant number of sexually immature pikeperch (Sander lucioperca) individuals have been identified in size and age categories that are expected to be sexually mature. To explore if this phenomenon is attributed to estrogenic endocrine disruption, we conducted a comprehensive study comparing fish from lake Pyhäjärvi with those from a nearby reference lake, lake Näsijärvi. Roach (Rutilus rutilus), known for its susceptibility to EDCs, was also included for comparison. We examined various parameters in both pikeperch and roach, including size, condition factor, age, reproductive indicators, biometric indices and gonadal histology. We also assessed liver vitellogenin mRNA levels and genetic sex in roach, and measured estrogen levels in lake waters and wastewater treatment plant effluents. Results revealed that approximately one-third of fish in both species exhibited sexual immaturity in lake Pyhäjärvi, with a female-biased sex ratio. Surprisingly, we found no signs of estrogenic endocrine disruption, indicated by the absence of intersex fish in both species. Furthermore, vitellogenin levels in roach closely resembled those in the reference lake. Estrogens were undetectable in the lake waters, suggesting that factors other than estrogenic EDCs, including other potential endocrine disruptors such as PCBs or heavy metals, may be influencing delayed sexual maturity and skewed sex ratios. Further inquiry is needed to pinpoint these underlying causes. Our study provides essential baseline information on fish sexual development in lake Pyhäjärvi, emphasizing the need for ongoing monitoring and research to understand delayed sexual maturity and biased sex ratios. This is vital given the increasing concern about EDC impacts on aquatic ecosystems and the necessity for effective management strategies to protect these ecosystems' health and integrity.