Novel male exposure reduces uterine e-cadherin, increases uterine luminal area, and diminishes progesterone levels while disrupting blastocyst implantation in inseminated mice

• We examined estrogen-dependent uterine mechanisms in the Bruce effect.
• Male exposure reduced implantation sites during gestation days 4–8.
• Uterine luminal area was greater in male-exposed females than in controls.
• Uterine e-cadherin was reduced in male-exposed females.
• Reduced uterine closure and e-cadherin are consistent with estrogenic activity.

Exposure to novel male mice disrupts blastocyst implantation in inseminated female mice, and evidence increasingly implicates the female's absorption of male urinary estrogens. We observed implantation sites in male-exposed and isolated control female mice during gestation days (GD) 2–8, observing a significant reduction in male-exposed females compared to controls, particularly on GD 6 and 8. We also measured transitions in uterine luminal area and e-cadherin expression, as these processes are modulated by estrogens. Luminal area was greater in male-exposed females than in controls during the post-implantation period (GD 5–7). E-cadherin levels were suppressed by male exposure, particularly during GD 4–6 Serum progesterone levels were also reduced in male-exposed females. The effects of male exposure on uterine closure and e-cadherin levels are consistent with established effects of estrogens, and suggest a possible mechanism that could contribute to implantation failure.This article is part of a Special Issue entitled ‘Pregnancy and Steroids’.