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. 2021 Mar 23;45(6):1170–1192. doi: 10.1038/s41366-021-00790-w

Table 7.

Excess androgens during gestation and its effect on offspring adiposity.

Study Species Maternal manipulation Duration Offspring diet Offspring sex Offspring age Adipose structure Adipose molecular Whole body changes
Nohara et al. [136] Mice Testosterone (100 μg) Vs control Neonatal days 1 and 2 Chow diet Female 6 weeks ↑ Dysfunctional WAT ↑ Number of enlarged insulin-resistant adipocytes ↑ Dysfunctional BAT ↑ BAT mass ↓ Energy expenditure. Leptin resistance hypoadiponectinemia.
Gulan et al. [137] Rats Testosterone (0.5 mg/g/day) Vs control GD15–Term Chow diet Female 8 weeks ↑ Pro-inflammatory cytokines (IL-1β, IL-18, and MCP-1) ↑ Body weight ↑ Serum levels of testosterone, insulin, and leptin ↓ Adiponectin levels
HFHS diet (compared to chow control) ↑ Pro-inflammatory cytokines (IL-1β, IL-18, IL-6, TNF-α and MCP-1) ↑ Body weight
Nilsson et al. [134] Rats Testosterone (1 mg) Vs control 1 injection 3 h after birth Chow diet Female 10 weeks ↓ Parametrial, retroperitoneal, and inguinal adipose tissue mass ↑ Mesenteric adipose tissue mass NA ↑ Body weight
Xu et al. [133] Rhesus Monkeys Testosterone (1 mg) Vs control 40 consecutive days beginning on GD40–GD44 Female 9 weeks NA 163 differentially methylated CPG islands in VAT Altered pathways included TGF-β, Wnt/ β-catenin, and antiproliferative signaling
Puttabyatappa et al. [132] Sheep Testosterone (100 mg) Vs control GD30–GD90 twice weekly Standard diet Female 21 months ↓Adipocyte size ↓ ADIPOQ mRNA in VAT ↑ ADIPOQ mRNA in SAT ↑ TNF-a, CCL2 mRNA in VAT and SAT ↑ IL1B mRNA in VAT
Lu et al. [135] Sheep Testosterone (100 mg) Vs control GD30–GD90 twice weekly Standard diet Female 2 years NA ↑ p-mTOR

Ad Lib ad libitum feeding, BAT brown adipose tissue, GD gestational day, HFD high-fat diet, NA not applicable, SAT subcutaneous adipose tissue, VAT visceral adipose tissue, Vs versus, WAT white adipose tissue.