Developmental plasticity in thyroid function primed by maternal hyperleptinemia in early lactation: a time-course...

Area of Science:

• Endocrinology
• Developmental Biology
• Reproductive Biology

Background:

• Maternal leptin exposure during late lactation is linked to adult thyroid dysfunction in offspring.
• The impact of early-life maternal leptin treatment on offspring thyroid development remains largely unexplored.
• Maternal obesity is associated with hyperleptinemia, raising concerns about offspring developmental outcomes.

Purpose of the Study:

• To investigate the effects of maternal leptin administration during the initial 10 days of lactation on offspring thyroid function.
• To assess thyroid hormone levels (T3, T4, TSH) and liver mitochondrial glycerolphosphate dehydrogenase (mGPD) activity in offspring at various developmental stages (21, 30, 180 days).
• To determine if early-life maternal hyperleptinemia can program long-term thyroid dysfunction.

Main Methods:

• Lactating Wistar rats received daily subcutaneous leptin injections (8 μg/100 g body weight) or saline (control) for the first 10 days postpartum.
• Offspring were analyzed at 21, 30, and 180 days old for serum and milk thyroid hormone and leptin levels.
• Liver mitochondrial glycerolphosphate dehydrogenase (mGPD) activity was measured as an indicator of thyroid hormone action.

Main Results:

• Leptin-treated mothers exhibited higher milk T3 levels; their offspring showed elevated serum T3 and TSH at the end of lactation.
• At 30 days old, leptin-exposed offspring displayed reduced TSH, T3, and mGPD activity, indicating transient hypothyroidism.
• Adult offspring (180 days) from leptin-treated mothers presented hyperleptinemia, increased serum T3, and decreased mGPD activity, suggesting altered thyroid regulation.

Conclusions:

• Maternal hyperleptinemia during lactation induces hypothyroidism in early life and may program for elevated thyroid hormone levels in adulthood.
• These findings highlight the potential long-term consequences of maternal hyperleptinemia, common in obesity, on offspring thyroid health.
• Early-life endocrine disruption via maternal leptin can have lasting impacts on metabolic and thyroid function, contributing to future disease risk.