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Women with obesity have higher risk of adverse pregnancy outcomes, including preeclampsia (PE). Late-gestational hypertension, aberrant fetoplacental development, and fetal growth restriction (FGR), hallmarks of PE, are observed spontaneously in BPH/5 mice. Similar to obese preeclamptic women, BPH/5 mice have higher visceral white adipose tissue (WAT) and circulating leptin. We hypothesized that attenuation of maternal obesity and serum leptin in pregnant BPH/5 mice will improve fetoplacental development by decreasing hypoxia markers and leptin expression at the maternal-fetal interface. Methods: To test this hypothesis, BPH/5 mice were fed ad libitum (lib) and pair-fed (PF) to C57 ad lib controls beginning at embryonic day (e) 0.5. Hypoxia-related genes, hypoxia inducible factor (Hif) 1a, stem cell factor (Scf), heme oxygenase-1 (Ho-1), leptin (Lep), and leptin receptor (LepR) were assessed in e7.5 implantation sites. Results: BPH/5 ad lib had 1.5 to 2-fold increase in Hif1a, Scf, and Ho-1 mRNA and a greater than 3-fold increase in leptin mRNA vs. C57 that was attenuated with PF. Exogenous leptin promoted Hif1a and Ho-1 mRNA expression in e7.5 decidua in vitro. While hypoxic conditions in vitro did not change decidual leptin mRNA. Furthermore, BPH/5 PF mice demonstrated improved fetal and placental outcomes later in gestation, with greater placental vascular area by e18.5 and attenuation of FGR. Conclusion: In conclusion, pair-feeding BPH/5 mice beginning at conception may improve placental vasculature formation via decreased leptin and hypoxia-associated markers in this model. Future investigations are needed to better determine the effect of hypoxia and leptin on pregnancy outcomes in obese pregnant women. [ABSTRACT FROM AUTHOR]

The objective of this experiment was to determine if incorporation of kisspeptin-10 (Kp10) into treatment with estradiol benzoate (EB) and sulpiride to induce early cyclicity would result in greater endocrine responses and a greater number of mares responding with either follicle(s) > 30 mm or ovulation within 25 days of treatment. Eighteen anestrous mares were blocked by breed, body condition, and age before random assignment to treatment or control. All mares received 50 mg EB before receiving osmotic minipumps containing either saline (n = 9) or Kp10 (50 μg/hour; n = 9) one day later. The next day, all mares received 3 g sulpiride. Serial blood sampling occurred after pump placement and continued daily for 25 days. Transrectal ultrasounds were performed regularly to monitor ovarian activity. Data were analyzed by Student's t-test or ANOVA with repeated measures. Seven Kp10-treated mares responded compared to only 4 saline-treated mares. Mean days from sulpiride treatment to ovarian response was less in Kp10-treated mares (13.7 ± 1.1 d, P ≤ 0.01) compared to saline-treated mares (35.9 ± 7.8 d). Plasma prolactin increased (P < 0.001) in response to sulpiride in all mares; however, prolactin was higher (P < 0.05) in Kp10-treated mares. Plasma LH increased in all mares beginning 5 days after sulpiride but was greater (P < 0.0001) in Kp10-treated mares. Plasma FSH concentrations did not differ between groups. In conclusion, incorporation of Kp10 potentiated the prolactin and LH responses to EB-sulpiride and resulted in more mares responding with early ovarian activity., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

AbstractPreeclampsia (PE) is a hypertensive disorder that impacts 2-8% of pregnant women worldwide. It is characterized by new onset hypertension during the second half of gestation and is a leading cause of maternal and fetal morbidity/mortality. Maternal obesity increases the risk of PE and is a key predictor of childhood obesity and potentially offspring cardiometabolic complications in a sex-dependent manner. The influence of the maternal obesogenic environment, with superimposed PE, on offspring development into adulthood is unknown. Obese BPH/5 mice spontaneously exhibit late-gestational hypertension, fetal demise and growth restriction, and excessive gestational weight gain. BPH/5 females have improved pregnancy outcomes when maternal weight loss via pair-feeding is imposed beginning at conception. We hypothesized that phenotypic differences between female and male BPH/5 offspring can be influenced by pair feeding BPH/5 dams during pregnancy. BPH/5 pair-fed dams have improved litter sizes and increased fetal body weights. BPH/5 offspring born to ad libitum dams have similar sex ratios, body weights, and fecal microbiome as well as increased blood pressure that is reduced in the dam pair-fed offspring. Both BPH/5 male and female offspring born to pair-fed dams have a reduction in adiposity and an altered gut microbiome, while only female offspring born to pair-fed dams have decreased circulating leptin and white adipose tissue inflammatory cytokines. These sexually dimorphic results suggest that reduction in the maternal obesogenic environment in early pregnancy may play a greater role in female BPH/5 sex-dependent cardiometabolic outcomes than males. Reprograming females may mitigate the transgenerational progression of cardiometabolic disease., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Preeclampsia (PE) is a life-threatening human gestational syndrome with incompletely understood etiopathogenesis. The disorder has a spectrum of clinical features, likely due to a complex interaction between maternal predisposing factors and abnormalities at the maternal-fetal interface. Poor trophoblast cell invasion, inadequate uterine vascular remodeling, and placental hypoperfusion are considered as key placental events leading to PE. Kisspeptins, a family of small peptides derived from the KISS1 gene, have been implicated in the development of this syndrome. Most studies of kisspeptin expression in PE have reported an upregulation of kisspeptins and/or their cognate receptor in preeclamptic placentas. Conversely, maternal peripheral blood concentration of kisspeptins is reportedly lower in PE than in uncomplicated pregnancies. This apparent paradox remains to be further elucidated. Although kisspeptins were initially known for inhibiting cellular migration and invasion, other biological activities attributed to these peptides include neuroendocrine regulation of reproduction, metabolism regulation, inhibition of angiogenesis, and induction of apoptosis. This review summarizes the current knowledge on expression and biological activity of kisspeptins at the maternal-fetal interface in the context of PE.