de Souza, G. O. | Search bioRxiv

bioRxiv2026

Reproductive experience promotes permanent body growth independently of growth hormone

Pregnancy leads to many adaptations in the maternal body, some of which are reversible. However, reproductive experience can also result in permanent effects. Here, we investigated how pregnancy influences the somatotrophic system and the lasting effects of reproductive experience on the maternal organism. Reproductive experience induced a pronounced increase in lean body mass and longitudinal growth in both wild-type and growth hormone (GH)-deficient mice compared with age-matched virgins. Body growth was primarily observed during the first pregnancy, whereas a second gestation was mostly associated with increased adiposity. Increased GH secretion was observed in pregnant wild-type mice but not in pregnant GHRHR-deficient mice. Pregnancy-induced body growth is preserved despite disruption of GH-, ghrelin-, and estrogen-related signaling pathways. Data from a cohort of women with isolated GH deficiency (IGHD) caused by a loss-of-function mutation in the GHRHR gene revealed that nulliparous women were 7 cm shorter than those with one or more pregnancies. In conclusion, reproductive experience induces permanent changes in the maternal organism, promoting body growth in models that allow this response. Pregnancy-induced body growth appears to be independent of GH action. These findings underscore the need for further studies to investigate the long-lasting consequences of reproductive experience in females.

physiology↗

bioRxiv2025

Profile of proteins involved in iron homeostasis and energy metabolism in multiple organs of leptin-deficient mice

Obesity is a global health problem. Its impacts are even more alarming when consider associated comorbidities, which include iron deficiency. Despite the importance of iron in metabolic function, the relationship between iron deficiency and metabolic dysregulation in obesity has not been fully addressed. Here, we evaluated the proteins involved in iron homeostasis and metabolism in multiple organs of leptin-deficient obese mice, a model that allows investigation of the progression of obesity. In the liver, proteins involved in glycaemia control were altered in both 3- and 5-month-old ob/ob mice (3mOB and 5mOB), but intracellular iron storage was reduced only in 3mOB. In the serum samples, glucose and cholesterol were increased in both 3mOB and 5mOB, with no alterations in iron markers. The pattern of liver proteins and serum metabolites indicate insulin-resistance state and glycemia dysregulation. In adipose tissue, 3mOB showed increased citrate synthase levels, while 5mOB showed increased MTCO2 and reduced ATP synthase levels. Ferritin was increased only in 5mOB. In the hippocampus, one of the most affected brain regions in obesity, increased MTCO2 and reduced ATP synthase levels were observed in 3mOB, while in 5mOB, increased OXCT1, a key enzyme for ketone body utilization, was observed. Reduction of ferritin levels was observed only in 5mOB. Thus, at 5 months, when the animals develop severe obesity, iron accumulates in adipose tissue but shows a reduction in the hippocampus. Our findings suggest that iron homeostasis is disrupted in a tissue-specific manner, with altered protein profiles that indicate metabolic dysregulation in multiple organs.

biochemistry↗