Maternal progesterone and adipose mPRε in pregnancy regulate the embryonic nutritional state

Watanabe, K.; Yamano, M.; Miyamoto, J.; Ohue-Kitano, R.; Masujima, Y.; Sasahara, D.; Mouri, Y.; Kono, N.; Inuki, S.; Osakada, F.; Nagaoka, K.; Aoki, J.; Sugiura, Y.; Ohno, H.; Kondoh, E.; Kimura, I.

doi:10.1101/2024.08.26.609823

bioRxiv · 10.1101/2024.08.26.609823

Maternal progesterone and adipose mPRε in pregnancy regulate the embryonic nutritional state

Watanabe, K.·Yamano, M.·Miyamoto, J.·Ohue-Kitano, R.·Masujima, Y.·Sasahara, D.·Mouri, Y.·Kono, N.·Inuki, S.·Osakada, F.·Nagaoka, K.·Aoki, J.·Sugiura, Y.·Ohno, H.·Kondoh, E.·Kimura, I.

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Abstract

Sex steroid hormones such as progesterone play a pivotal role in reproductive functions and maintaining pregnancy; however, the impact of progesterone on the interaction between mother and embryo is unclear. Here, we demonstrate that the relationship between maternal progesterone and membrane progesterone receptor epsilon (mPR{varepsilon}) in adipose tissue regulates embryonic nutritional environment and growth after birth in mice. The activation of adipose mPR{varepsilon} by increased progesterone during pregnancy enhanced maternal insulin resistance through the production of prostaglandins, thereby efficiently providing glucose to embryos. The offspring of mPR{varepsilon}-deficient mothers exhibited metabolic dysfunction, whereas mPR{varepsilon}-deficient mothers with high-fat-diet-induced obesity exhibited improved insulin sensitivity. These findings establish the importance of progesterone as a nutritional regulator between mother and embryo, and suggest that mPR{varepsilon} modulators could be developed to treat pregnant glycemic control disorders such as gestational diabetes mellitus, as well as metabolic syndrome in offspring. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/609823v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@1ecd968org.highwire.dtl.DTLVardef@b5492aorg.highwire.dtl.DTLVardef@1d692ecorg.highwire.dtl.DTLVardef@47de8a_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Watanabe, K., Yamano, M., Miyamoto, J., Ohue-Kitano, R., Masujima, Y., Sasahara, D., Mouri, Y., Kono, N., Inuki, S., Osakada, F., Nagaoka, K., Aoki, J., Sugiura, Y., Ohno, H., Kondoh, E., Kimura, I.. 2024-08-27. Maternal progesterone and adipose mPRε in pregnancy regulate the embryonic nutritional state. https://doi.org/10.1101/2024.08.26.609823

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